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| Name | Class |
|---|---|
| Virginia Commonwealth University | OTHER |
| NYU Langone Health | OTHER |
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Neurogenic osteoporosis is a common complication of spinal cord injury (SCI) that is associated with low impact bone fractures. It is concerning that more than 46,000 Veterans affected with SCI and are at risk of osteoporosis and possible low impact fractures. About fifty percent of all individuals with SCI will develop low impact fracture in their life time. The management of osteoporosis-related fractures can impose substantial economic burden on the health care system, the individual and the families. Previous studies did not succeed in reversing the process of bone loss after SCI. In the present pilot study, we will evaluate the effect of Neuromuscular Electrical Stimulation Resistance Training in combination with oral Vitamin D supplementation, on bone quality in Veterans with chronic SCI, using a randomized experimental design.
Neurogenic osteoporosis is a devastating problem that is likely to impact 46,000 Veterans with chronic spinal cord injury (SCI). It is typically associated with low impact fractures of long bones and other medical comorbidities. It is estimated that approximately fifty percent of all individuals with SCI will develop low impact fracture during their lifetime. The management of osteoporosis related fractures can impose substantial economic burden on the health care system, individuals with SCI and their families. Advancement in medical research clearly indicated that neurogenic osteoporosis is linked to reduced loading and Vitamin D (Vit D) deficiency. Our pilot work indicated that a simple rehabilitation paradigm targeting towards evoking skeletal muscle hypertrophy may attenuate deterioration in trabecular bone parameters after SCI. Evoked resistance training (RT) using surface neuromuscular electrical stimulation (NMES) has been shown as a successful and feasible home-based approach to load skeletal muscles after SCI. Our earlier results may imply long-term compliance and adherence if successfully applied in conjunction with a telehealth approach. In the present study, we propose a simple home-based approach of using NMES RT in conjunction with oral Vit D supplementation on trabecular bone quality in 20 Veterans with chronic SCI. Data will include measurements of trabecular bone quality as determined by magnetic resonance imaging (MRI) and bone biomarkers associated with the process of bone remodeling.
Twenty participants with chronic (> 1-year post-injury) motor complete (AIS A and B) SCI (18 to 65 years of age) will be randomly assigned into either NMES RT plus 2000IU of Vit D (10 participants) or passive movement plus 2000IU Vit D (10 participants) to participate in a repeated measure design trial for 9 months. The NMES RT plus Vit D will undergo 4.5 months of open kinematic chain resistance training followed by 4.5 months of closed kinematic chain using simple rowing approach. This pilot work will have two main specific aims. Aim 1. To determine the impact of home-based NMES RT protocol plus oral Vit D supplementation compared to passive movement plus oral Vit D on bone microarchitectural properties. Aim 2. To determine the impact of home-based NMES RT protocol plus oral Vit D compared to passive movement and Vit D supplementation on biomarkers of bone formation and bone resorption.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| NMES Plus Vitamin D | Experimental | Subjects will undergo 4.5 months of open kinematic chain resistance training followed by 4.5 months of closed kinematic chain using simple rowing approach and 2000IU oral vitamin D supplementation daily for 9 months. |
|
| Passive movement plus vitamin D | Active Comparator | Subjects will undergo 9 months of simple passive movement exercise at home and 2000IU oral vitamin D supplementation daily for 9 months. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| NMES | Device | Subjects will undergo 4.5 months of open kinematic chain resistance training followed by 4.5 months of closed kinematic chain using simple rowing approach |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in Trabecular Plate Width (Tb.PW) for Femur and Tibia at 4.5 Months | The outcome measure was trabecular plate width expressed in μm, as measured by a non-contrast magnetic resonance imaging (MRI) of the femur and tibia. A trained radiology technician performed the MRI using a 3.0T magnet (GE Discovery MR750 software, version: DV24 System 804675VA3T; GE Waukesha, WI). A specific knee coil with a 3D fast-spin gradient echo (10 min) sequence was used to obtain high-resolution images (20-22 FOV). A bilateral phased array coil (USA Instruments) was used to collect 30 contiguous 1-mm slices in the axial plane, starting with the distal end of the femur, and another block of 30 starting with the proximal end of the tibia. The metric used was the median change from baseline to 4.5 months and 9 months, respectively. Higher values indicate improved bone trabeculae. | 4.5 months |
| Change in Trabecular Plate Width (Tb.PW) for Femur and Tibia at 9 Months | The outcome measure was trabecular spacing expressed in μm, as measured by a non-contrast magnetic resonance imaging (MRI) of the femur and tibia. A trained radiology technician performed the MRI using a 3.0T magnet (GE Discovery MR750 software, version: DV24 System 804675VA3T; GE Waukesha, WI). A specific knee coil with a 3D fast-spin gradient echo (10 min) sequence was used to obtain high-resolution images (20-22 FOV). A bilateral phased array coil (USA Instruments) was used to collect 30 contiguous 1-mm slices in the axial plane, starting with the distal end of the femur, and another set of 30 slices starting with the proximal end of the tibia. The metric used was the median change from baseline to 9 months. Higher values indicate improved Tb. PW. | 9 months |
| Change in Trabecular Spacing (Tb.Sp) for Femur and Tibia at 4.5 Months | The outcome measure was trabecular spacing expressed in μm, as measured by a non-contrast magnetic resonance imaging (MRI) of the femur and tibia. The metric used was the median change from baseline to 4.5 months and 9 months, respectively. Higher values indicate poorer bone health. A trained radiology technician performed the MRI using a 3.0T magnet (GE Discovery MR750 software, version: DV24 System 804675VA3T; GE Waukesha, WI). A specific knee coil with a 3D fast-spin gradient echo (10 min) sequence was used to obtain high-resolution images (20-22 FOV). A bilateral phased array coil (USA Instruments) was used to collect 30 contiguous 1-mm slices in the axial plane, starting with the distal end of the femur, and another block of 30 starting with the proximal end of the tibia. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Bone Mineral Density in Distal Femur as Measured by Dual Energy X-ray Absorptiometry (DXA) Scan | A dual-energy X-ray absorptiometry scan was performed by a trained technologist using a General Electric iDXA scanner (GE Lunar Inc., Madison, WI) at baseline, 4.5 months, and at 9 months. The scanner was calibrated using a phantom calibration box that mimics human tissues to assess scan precision and reliability. All participants had their jewelry removed before being placed supine on the scanning table with their arms internally rotated and palms facing medially. Participants received scans in the region of interest on both sides (L & R) of the body (hip, knee), as well as the lumbar spine. |
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Inclusion Criteria:
To be included, participants will have to:
Exclusion Criteria:
Potential participants will be excluded if they exhibit any of the following:
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| Name | Affiliation | Role |
|---|---|---|
| Dora E Ifon, PhD | Hunter Holmes McGuire VA Medical Center, Richmond, VA | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hunter Holmes McGuire VA Medical Center, Richmond, VA | Richmond | Virginia | 23249-0001 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33443609 | Background | Holman ME, Chang G, Ghatas MP, Saha PK, Zhang X, Khan MR, Sima AP, Adler RA, Gorgey AS. Bone and non-contractile soft tissue changes following open kinetic chain resistance training and testosterone treatment in spinal cord injury: an exploratory study. Osteoporos Int. 2021 Jul;32(7):1321-1332. doi: 10.1007/s00198-020-05778-2. Epub 2021 Jan 14. | |
| 33134108 |
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One participant was excluded prior to the start of the study because he failed to complete baseline screening and did not respond to phone calls.
Participants were recruited from a spinal cord injury outpatient clinic. One participant was referred by another participant.
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| ID | Title | Description |
|---|---|---|
| FG000 | NMES Plus Vitamin D | Subjects will undergo 4.5 months of open kinematic chain resistance training followed by 4.5 months of closed kinematic chain using simple rowing approach and 2000IU oral vitamin D supplementation daily for 9 months. NMES: Subjects will undergo 4.5 months of open kinematic chain resistance training followed by 4.5 months of closed kinematic chain using simple rowing approach Vitamin D: 2000IU oral vitamin D supplementation daily for 9 months |
| FG001 | Passive Movement Plus Vitamin D | Subjects will undergo 9 months of simple passive movement exercise at home and 2000IU oral vitamin D supplementation daily for 9 months. Vitamin D: 2000IU oral vitamin D supplementation daily for 9 months Passive movement: Subjects will perform simple passive movement exercise for their legs while sitting in their wheelchairs at their home. The frequency of the training will be twice weekly. . |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Six individuals participated in the study. Two participants withdrew after the first phase of the trial (one in the Passive movement plus vitamin D (PM + D), and the other in the NMES + Vit. D group, respectively. As a result, the final number of participants analyzed at 9 months were 4 (3 in the NMES + D group and 1 in the PM + D group).
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| ID | Title | Description |
|---|---|---|
| BG000 | NMES Plus Vitamin D | Subjects will undergo 4.5 months of open kinematic chain resistance training followed by 4.5 months of closed kinematic chain using simple rowing approach and 2000IU oral vitamin D supplementation daily for 9 months. NMES: Subjects will undergo 4.5 months of open kinematic chain resistance training followed by 4.5 months of closed kinematic chain using simple rowing approach Vitamin D: 2000IU oral vitamin D supplementation daily for 9 months |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in Trabecular Plate Width (Tb.PW) for Femur and Tibia at 4.5 Months | The outcome measure was trabecular plate width expressed in μm, as measured by a non-contrast magnetic resonance imaging (MRI) of the femur and tibia. A trained radiology technician performed the MRI using a 3.0T magnet (GE Discovery MR750 software, version: DV24 System 804675VA3T; GE Waukesha, WI). A specific knee coil with a 3D fast-spin gradient echo (10 min) sequence was used to obtain high-resolution images (20-22 FOV). A bilateral phased array coil (USA Instruments) was used to collect 30 contiguous 1-mm slices in the axial plane, starting with the distal end of the femur, and another block of 30 starting with the proximal end of the tibia. The metric used was the median change from baseline to 4.5 months and 9 months, respectively. Higher values indicate improved bone trabeculae. | Participants (n = 6) with chronic motor-complete spinal cord injury (C8-T10) with ASIA impairment classification of A or B, completed an MRI at baseline and 4.5 months. | Posted | Median | Inter-Quartile Range | μm | 4.5 months |
|
Four weeks. This was a spontaneous reporting by the participant. The participant was followed and monitored by his SCI provider over the 4 weeks period, while research staff maintained weekly contact for updates on participant's healing process.
One participant in the intervention group reported opening of an old ischial wound scar (grade II) due sitting longer than usual on a commode for routine bowel care program.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | NMES Plus Vitamin D | Subjects will undergo 4.5 months of open kinematic chain resistance training followed by 4.5 months of closed kinematic chain using simple rowing approach and 2000IU oral vitamin D supplementation daily for 9 months. NMES: Subjects will undergo 4.5 months of open kinematic chain resistance training followed by 4.5 months of closed kinematic chain using simple rowing approach Vitamin D: 2000IU oral vitamin D supplementation daily for 9 months |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Disruption in skin integrity | Skin and subcutaneous tissue disorders | Systematic Assessment | One participant reported opening of an ischial wound scar (grade II) due to sitting for a prolonged period of time on a commode to do his bowel care. |
The small sample size, only male participants, and a wide variation in participants' level of injury (C8-T10) and age, limit generalizability of the study findings to a broader spinal cord injury population.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dora E. Ifon | McGuire VA Hospital | 804-675-5455 | dora.ifon@va.gov |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jun 22, 2021 | Jun 7, 2025 | Prot_SAP_001.pdf |
| ICF | No | No | Yes | Informed Consent Form | Aug 17, 2021 | Jul 11, 2024 | ICF_000.pdf |
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| ID | Term |
|---|---|
| D013119 | Spinal Cord Injuries |
| ID | Term |
|---|---|
| D013118 | Spinal Cord Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D020196 | Trauma, Nervous System |
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| ID | Term |
|---|---|
| D008722 | Methods |
| D014807 | Vitamin D |
| D016059 | Range of Motion, Articular |
| ID | Term |
|---|---|
| D008919 | Investigative Techniques |
| D012632 | Secosteroids |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
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There are two groups
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|
| Vitamin D | Drug | 2000IU oral vitamin D supplementation daily for 9 months |
|
|
| Passive movement | Behavioral | Subjects will perform simple passive movement exercise for their legs while sitting in their wheelchairs at their home. The frequency of the training will be twice weekly |
|
|
| 4.5 months |
| Change in Trabecular Spacing (Tb.Sp) for Femur and Tibia at 9 Months | The outcome measure was trabecular plate width expressed in μm, as measured by a non-contrast magnetic resonance imaging (MRI) of the femur and tibia. A trained radiology technician performed the MRI using a 3.0T magnet (GE Discovery MR750 software, version: DV24 System 804675VA3T; GE Waukesha, WI). A specific knee coil with a 3D fast-spin gradient echo (10 min) sequence was used to obtain high-resolution images (20-22 FOV). A bilateral phased array coil (USA Instruments) was used to collect 30 contiguous 1-mm slices in the axial plane, starting with the distal end of the femur, and another block of 30 beginning with the proximal end of the tibia. The metric used was the median change from baseline to 4.5 months and 9 months, respectively. Higher values indicate improved bone trabeculae. | 9 months |
| Change in Trabecular Network Area Density (Tb.NA) Measured in mm^2/mm^3) at 4.5 Months | The outcome measure was trabecular network area density expressed in mm^2/mm^3, as measured by a non-contrast magnetic resonance imaging (MRI) of the femur and tibia. The metric used was the median change from baseline to 4.5 months and 9 months, respectively. Higher values indicate improved bone trabeculae network area density. A trained radiology technician performed the MRI using a 3.0T magnet (GE Discovery MR750 software, version: DV24 System 804675VA3T; GE Waukesha, WI). A specific knee coil with a 3D fast-spin gradient echo (10 min) sequence was used to obtain high-resolution images (20-22 FOV). A bilateral phased array coil (USA Instruments) was used to collect 30 contiguous 1-mm slices in the axial plane, starting with the distal end of the femur, and another block of 30 starting with the proximal end of the tibia. | 4.5 months |
| Change in Trabecular Network Area Density (Tb.NA) as Measured by MRI at 9 Months | The outcome measure was trabecular network area density expressed in mm^2/mm^3, as measured by a non-contrast magnetic resonance imaging (MRI) of the femur and tibia. The metric used was the median change from baseline to 4.5 months and 9 months, respectively. Higher values indicate improved bone trabeculae network area density. A trained radiology technician performed the MRI using a 3.0T magnet (GE Discovery MR750 software, version: DV24 System 804675VA3T; GE Waukesha, WI). A specific knee coil with a 3D fast-spin gradient echo (10 min) sequence was used to obtain high-resolution images (20-22 FOV). A bilateral phased array coil (USA Instruments) was used to collect 30 contiguous 1-mm slices in the axial plane, starting with the distal end of the femur, and another block of 30 starting with the proximal end of the tibia. | 9 months |
| 4.5 months |
| Change in Distal Femur Bone Mineral Density | A dual-energy X-ray absorptiometry scan was performed by a trained technologist using a General Electric iDXA scanner (GE Lunar Inc., Madison, WI) at baseline, 4.5 months, and at 9 months. The scanner was calibrated using a phantom calibration box that mimics human tissues to assess scan precision and reliability. All participants had their jewelry removed before being placed supine on the scanning table with their arms internally rotated and palms facing medially. Participants received scans in the region of interest on both sides (L & R) of the body (hip, knee), as well as the lumbar spine. | 9 months |
| Change in Proximal Tibia Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) Scan | A dual-energy X-ray absorptiometry scan was performed by a trained technologist using a General Electric iDXA scanner (GE Lunar Inc., Madison, WI) at baseline, 4.5 months, and at 9 months. The scanner was calibrated using a phantom calibration box that mimics human tissues to assess scan precision and reliability. All participants had their jewelry removed before being placed supine on the scanning table with their arms internally rotated and palms facing medially. Participants received scans in the region of interest on both sides (L & R) of the body (hip, knee), as well as the lumbar spine. | 4.5 months |
| Change in Proximal Tibia Bone Mineral Density as Measured by a Dual-energy X-ray Absorptiometry (DXA) Scan | A dual-energy X-ray absorptiometry scan was performed by a trained technologist using a General Electric iDXA scanner (GE Lunar Inc., Madison, WI) at baseline, 4.5 months, and at 9 months. The scanner was calibrated using a phantom calibration box that mimics human tissues to assess scan precision and reliability. All participants had their jewelry removed before being placed supine on the scanning table with their arms internally rotated and palms facing medially. Participants received scans in the region of interest on both sides (L & R) of the body (hip, knee), as well as the lumbar spine. | 9 months |
| Change in Bone Formation Marker - Procollagen Type 1 N-terminal Propeptide (P1NP) in mcg/L | Fasting blood samples were collected by venipuncture by the same individual at roughly the same time of day and under similar conditions to evaluate P1NP, a marker of bone formation. Samples were analyzed at Quest Diagnostics (Nichols Institute, Chantilly, VA). The reference range for P1NP is 30-110 mcg/L, and an increase indicates poor bone health. | 4.5 months |
| Change in Bone Formation Marker - Procollagen Type 1 Intact N-Propeptide (P1NP) Measured in mcg/L | Fasting blood samples were collected by venipuncture by the same individual at roughly the same time of day and under similar conditions to evaluate P1NP, a marker of bone formation. Samples were analyzed at Quest Diagnostics (Nichols Institute, Chantilly, VA). The reference range for P1NP is 30-110 mcg/L, and an increase indicates poor bone health. | 9 months |
| Change in Bone Resorption Marker-C-telopeptide of Type I Collagen (CTX) | CTX is a biochemical marker of bone resorption. Fasting blood samples were collected from participants via venipuncture by the same person at approximately the same time of day and under similar conditions to measure CTX (pg/mL). The samples were analyzed by Quest Diagnostics (Nichols Institute, Chantilly, VA). Sex and age-related reference ranges for males are: 18-29 years (87-1200), 30-39 years (70-780), 40-49 years (60-700), and 50-68 years (87-345). CTX is released into circulation when osteoclasts break down bone matrix; therefore, higher levels indicate increased osteoclastic activity and faster bone turnover. | 4.5 months |
| Change in Bone Resorption Marker-C-telopeptide of Type I Collagen (CTX) | CTX is a biochemical marker of bone resorption. Fasting blood samples were collected from participants via venipuncture by the same person at approximately the same time of day and under similar conditions to measure CTX (pg/mL). The samples were analyzed by Quest Diagnostics (Nichols Institute, Chantilly, VA). Sex and age-related reference ranges for males are as follows: 18-29 years (87-1200), 30-39 years (70-780), 40-49 years (60-700), and 50-68 years (87-345). CTX is released into circulation when osteoclasts break down bone matrix; therefore, higher levels indicate increased osteoclastic activity and faster bone turnover. | 9 months |
| Change in Serum 25-hydroxyvitamin D [25(OD)D] Level | 25-hydroxyvitamin D is the major circulating form of vitamin D and the most reliable biochemical indicator of an individual's vitamin D status. It is essential for maintaining bone strength, balance of minerals, and overall bone integrity. Adequate levels of 25(OH)D enhance intestinal calcium absorption for normal bone formation and remodeling. When vitamin D levels are low, calcium absorption decreases, leading to secondary hyperparathyroidism, which in turn increases bone resorption and weakens bone structure. The normal range is 32 to 100 ng/mL. Less than 20ng/mL is considered a deficiency, and 20 to 29 ng/mL is insufficiency. | 4.5 months |
| Change in Serum 25-hydroxyvitamin D Level | 25-hydroxyvitamin D is the main circulating form of vitamin D and the most reliable biochemical marker of an individual's vitamin D status. Vitamin D is crucial for maintaining bone strength, mineral balance, and overall bone health. Adequate levels of 25(OH)D improve intestinal calcium absorption, which is vital for normal bone formation and remodeling. When vitamin D levels are low, calcium absorption drops, leading to secondary hyperparathyroidism, which then increases bone resorption and weakens bone structure. The normal range is 32 to 100 ng/mL. Less than 20 ng/mL is considered a deficiency, and 20 to 29 ng/mL indicates insufficiency. | 9 months |
| Change in Quality-of-life Measure: Physical Health (Scored on 1-5 Likert Scale) | The secondary outcome measure was the WHO Quality of Life (WHOQOL)-BREF, a 26-item self-administered questionnaire developed by WHO to assess quality of life across four domains, including two general items. Each item is rated on a 5-point Likert scale (1 = negative or low perception, 5 = positive or high perception). The instrument includes four health domains: physical health, psychological health, social relationships, and environmental engagement. Physical health (7 items) evaluates energy, fatigue, sleep, mobility, pain, and activities of daily living. The maximum score for this domain is 100, and a higher score indicates a better quality of life. | 9 months |
| Change in Quality-of-life Measure- Psychological Health | The WHOQOL-BREF instrument was used to assess QOL in four domains of health, including: physical health, psychological health, social relationships, and environmental engagement. The mean scores of items within each domain were used to calculate domain scores, which were then transformed using the WHOQOL-BREF scoring manual to make the domain scores comparable to those used in the WHOQOL-100. Items 3, 4, and 26 were reverse-coded per the instruction manual. Psychological health (6 items) measures self-esteem, body image, negative and positive feelings, and concentration. A higher score denotes higher psychological health. | 9 months |
| Change in Quality-of-life Measure- Social Relationships Domain | The WHOQOL-BREF instrument was used to assess QOL in four domains of health, including: physical health, psychological health, social relationships, and environment. The mean scores of items within each domain were used to calculate domain scores, which were then transformed using the WHOQOL-BREF scoring manual to make the domain scores comparable to those used in the WHOQOL-100. Items 3, 4, and 26 were reverse-coded per the instruction manual. Social relationships (3 items) assess personal relationships, social support, and sexual life. A higher score denotes a higher social relationships. | 9 months |
| Change in Quality-of-life Measure-environmental Engagement Domain | The WHOQOL-BREF instrument was used to assess QOL in four domains of health participants, including: physical health, psychological health, social relationships, and environmental engagement. The mean scores of items within each domain were used to calculate domain scores, which were then transformed using the WHOQOL-BREF scoring manual to make the domain scores comparable to those used in the WHOQOL-100. Items 3, 4, and 26 were reverse-coded per the instruction manual. Environmental engagement (8 items) assesses financial resources, safety, home environment, health care access, and opportunities for recreation and learning. A Higher score denotes better environmental engagement. | 9 months |
| Ifon DE, Ghatas MP, Davis JC, Khalil RE, Adler RA, Gorgey AS. Long-term effect of intrathecal baclofen treatment on bone health and body composition after spinal cord injury: A case matched report. World J Orthop. 2020 Oct 18;11(10):453-464. doi: 10.5312/wjo.v11.i10.453. eCollection 2020 Oct 18. |
| BG001 | Passive Movement Plus Vitamin D | Subjects will undergo 9 months of simple passive movement exercise at home and 2000IU oral vitamin D supplementation daily for 9 months. Vitamin D: 2000IU oral vitamin D supplementation daily for 9 months Passive movement: Subjects will perform simple passive movement exercise for their legs while sitting in their wheelchairs at their home. The frequency of the training will be twice weekly. . |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Median | Inter-Quartile Range | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Baseline Trabecular plate width (Tb.PW) in μm as measured by MRI | Trabecular plate width, measured by a trained technician using non-contrast MRI of the femur and tibia with a 3.0T magnet (GE Discovery MR750 software, version: DV24 System 804675VA3T; GE Waukesha, WI). A specific knee coil with a 3D fast-spin gradient echo (10 min) sequence was used to obtain high-resolution images (20-22 FOV). A bilateral phased array coil (USA Instruments) was used to collect 30 contiguous 1-mm slices in the axial plane, starting with the distal end of the femur, and another set of 30 starting with the proximal end of the tibia. Metrics reported as median and IQR. | Median | Inter-Quartile Range | μm |
|
| Baseline Trabecular spacing (Tb.Sp) (um) as measured by MRI | Trabecular spacing in μm was measured by a non-contrast MRI of the femur and tibia by a trained technician using a 3.0T magnet (GE Discovery MR750 software, version: DV24 System 804675VA3T; GE Waukesha, WI). A specific knee coil with a 3D fast-spin gradient echo (10 min) sequence was used to obtain high-resolution images (20-22 FOV). A bilateral phased array coil (USA Instruments) was used to collect 30 contiguous 1-mm slices in the axial plane, starting with the distal end of the femur, and another set of 30 starting with the proximal end of the tibia. Median and IQR are reported. | Median | Inter-Quartile Range | μm |
|
| Baseline Trabecular network area density (Tb.NA) (mm^2/mm^3) measured by MRI | Trabecular network area density (mm^2/mm^3), measured with a non-contrast MRI, of the femur and tibia by a trained technician using a 3.0T magnet (GE Discovery MR750 software, version: DV24 System 804675VA3T; GE Waukesha, WI). A specific knee coil with a 3D fast-spin gradient echo (10 min) sequence was used to obtain high-resolution images (20-22 FOV). A bilateral phased array coil (USA Instruments) was used to collect 30 contiguous 1-mm slices in the axial plane, starting with the distal end of the femur, and another set of 30 starting with the proximal end of the tibia; median and IQR. | Median | Inter-Quartile Range | mm^2/mm^3 |
|
| Baseline Distal Femur Bone Mineral Density (BMD) in g/cm2 as measured by DXA | A dual-energy X-ray absorptiometry scan was performed by a trained technologist using a General Electric iDXA scanner (GE Lunar Inc., Madison, WI) at baseline, 4.5 months, and at 9 months. The scanner was calibrated using a phantom calibration box that mimics human tissues to assess scan precision and reliability. All participants had their jewelry removed before being placed supine on the scanning table with their arms internally rotated and palms facing medially. Participants received scans in the region of interest on both sides (L & R) of the body (hip, knee), as well as the lumbar spine. | Median | Inter-Quartile Range | g/cm2 |
|
| Baseline Proximal tibia Bone Mineral Density in g/cm2 as measured by DXA. | A dual-energy X-ray absorptiometry scan was performed by a trained technologist using a General Electric iDXA scanner (GE Lunar Inc., Madison, WI) at baseline, 4.5 months, and at 9 months. The scanner was calibrated using a phantom calibration box that mimics human tissues to assess scan precision and reliability. All participants had their jewelry removed before being placed supine on the scanning table with their arms internally rotated and palms facing medially. Participants received scans in the region of interest on both sides (L & R) of the body (hip, knee), as well as the lumbar spine. | Median | Inter-Quartile Range | g/cm2 |
|
| Baseline Bone formation marker (Procollagen Type 1 Intact N-Propeptide [P1NP] in mcg/L | Fasting blood samples were obtained by venopuncture by the same person at approximately the same time of day and under similar conditions to assess P1NP, a marker of bone formation. Specimens were analyzed by Quest Diagnostics (Nichols Institute, Chantilly, VA). The reference range for PINP is 30-110 mcg/L, and an increase denotes poor bone health. | Median | Inter-Quartile Range | mcg/L |
|
| Baseline Bone resorption marker (C-telopeptide of Type I collagen [CTX]), in pg/mL | CTX is a biochemical marker of bone resorption. Fasting blood samples were obtained from participants with venopuncture by the same person at approximately the same time of day and under similar conditions to measure CTX (pg/mL). Specimens were analyzed by Quest Diagnostics (Nichols Institute, Chantilly, VA). Sex and age-related reference ranges for males: 18-29yrs (87-1200), 30-39yrs (70-780), 40-49yrs (60-700), and 50-68yrs (87-345). CTX is released into the circulation when osteoclasts degrade bone matrix; thus, higher levels reflect increased osteoclastic activity and faster bone turnover. | Median | Inter-Quartile Range | pg/mL |
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| Baseline Serum concentration of 25-hydroxyvitamin D in ng/mL | 25 (OH)D is the main circulating form of vit. D, and the most reliable biochemical marker of an individual's vitamin D status. It is crucial for maintaining bone strength, mineral balance, and overall bone health. Adequate levels of 25(OH)D improve intestinal calcium absorption, which is vital for normal bone formation and remodeling. Low levels lead to decreased calcium absorption, resulting in secondary hyperparathyroidism, which in turn leads to increased bone resorption and weakening of the bone structure. Normal range is 32 to 100; < 20 ng/mL is deficiency, and 20 to 29 is insufficiency. | Median | Inter-Quartile Range | ng/mL |
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| Baseline Physical domain of Quality of life measure | The WHOQOL-BREF, a 26-item self-administered questionnaire, assesses quality of life across four domains, including two general items. Each item is rated on a 5-point Likert scale (1 = negative or low perception, 5 = positive or high perception). Physical health (7 items) evaluates energy, fatigue, sleep, mobility, pain, and activities of daily living. The maximum score for this domain is 100, and a higher score indicates better physical health. | Median | Inter-Quartile Range | units on a scale (0-100) |
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| Baseline Psychological health domain of Quality of life measure | The WHOQOL-BREF, a 26-item self-administered questionnaire, assesses quality of life across four domains, including two general items. Each item is rated on a 5-point Likert scale (1 = negative or low perception, 5 = positive or high perception). Psychological health (6 items) measures self-esteem, body image, negative and positive feelings, and concentration. The maximum score for this domain is 100, and a higher score indicates better psychological health. | Median | Inter-Quartile Range | units on a scale (0-100) |
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| Baseline Social relationship domain of Quality of life measure. | The WHOQOL-BREF, a 26-item self-administered questionnaire, assesses quality of life across four domains, including two general items. Each item is rated on a 5-point Likert scale (1 = negative or low perception, 5 = positive or high perception). Social relationships (3 items) assess personal relationships, social support, and sexual life. The maximum score for this domain is 100, and a higher score indicates a better quality of life in the social relationships domain. | Median | Inter-Quartile Range | units on a scale (0-100) |
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| Baseline environmental engagement domain of Quality of life measure. | The WHO Quality of Life (WHOQOL)-BREF, a 26-item self-administered questionnaire, assesses quality of life across four domains, including two general items. Each item is rated on a 5-point Likert scale (1 = negative or low perception, 5 = positive or high perception). Environmental engagement (8 items) assesses financial resources, safety, home environment, health care access, and opportunities for recreation and learning. The maximum score for this domain is 100, and a higher score indicates a better quality of life in the environmental domain. | Median | Inter-Quartile Range | units on a scale (0-100) |
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| OG000 | NMES Plus Vitamin D | Subjects will undergo 4.5 months of open kinematic chain resistance training followed by 4.5 months of closed kinematic chain using simple rowing approach and 2000IU oral vitamin D supplementation daily for 9 months. NMES: Subjects will undergo 4.5 months of open kinematic chain resistance training followed by 4.5 months of closed kinematic chain using simple rowing approach Vitamin D: 2000IU oral vitamin D supplementation daily for 9 months |
| OG001 | Passive Movement Plus Vitamin D | Subjects will undergo 9 months of simple passive movement exercise at home and 2000IU oral vitamin D supplementation daily for 9 months. Vitamin D: 2000IU oral vitamin D supplementation daily for 9 months Passive movement: Subjects will perform simple passive movement exercise for their legs while sitting in their wheelchairs at their home. The frequency of the training will be twice weekly. . |
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| Primary | Change in Trabecular Plate Width (Tb.PW) for Femur and Tibia at 9 Months | The outcome measure was trabecular spacing expressed in μm, as measured by a non-contrast magnetic resonance imaging (MRI) of the femur and tibia. A trained radiology technician performed the MRI using a 3.0T magnet (GE Discovery MR750 software, version: DV24 System 804675VA3T; GE Waukesha, WI). A specific knee coil with a 3D fast-spin gradient echo (10 min) sequence was used to obtain high-resolution images (20-22 FOV). A bilateral phased array coil (USA Instruments) was used to collect 30 contiguous 1-mm slices in the axial plane, starting with the distal end of the femur, and another set of 30 slices starting with the proximal end of the tibia. The metric used was the median change from baseline to 9 months. Higher values indicate improved Tb. PW. | Four participants with chronic motor-complete spinal cord injury (C8-T10) and an ASIA impairment classification of A or B completed MRI at 9 months (n = 3 in the NMES + Vit. D group and n = 1 in the Passive movement + Vit. D group). | Posted | Median | Inter-Quartile Range | um | 9 months |
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| Primary | Change in Trabecular Spacing (Tb.Sp) for Femur and Tibia at 4.5 Months | The outcome measure was trabecular spacing expressed in μm, as measured by a non-contrast magnetic resonance imaging (MRI) of the femur and tibia. The metric used was the median change from baseline to 4.5 months and 9 months, respectively. Higher values indicate poorer bone health. A trained radiology technician performed the MRI using a 3.0T magnet (GE Discovery MR750 software, version: DV24 System 804675VA3T; GE Waukesha, WI). A specific knee coil with a 3D fast-spin gradient echo (10 min) sequence was used to obtain high-resolution images (20-22 FOV). A bilateral phased array coil (USA Instruments) was used to collect 30 contiguous 1-mm slices in the axial plane, starting with the distal end of the femur, and another block of 30 starting with the proximal end of the tibia. | Six participants with chronic motor-complete spinal cord injury (C8-T10) and ASIA impairment classification of A or B completed MRI at 4.5 months (n = 4 in the NMES + Vit. D group and n = 2 in the Passive movement + Vit. D group). | Posted | Median | Inter-Quartile Range | um | 4.5 months |
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| Primary | Change in Trabecular Spacing (Tb.Sp) for Femur and Tibia at 9 Months | The outcome measure was trabecular plate width expressed in μm, as measured by a non-contrast magnetic resonance imaging (MRI) of the femur and tibia. A trained radiology technician performed the MRI using a 3.0T magnet (GE Discovery MR750 software, version: DV24 System 804675VA3T; GE Waukesha, WI). A specific knee coil with a 3D fast-spin gradient echo (10 min) sequence was used to obtain high-resolution images (20-22 FOV). A bilateral phased array coil (USA Instruments) was used to collect 30 contiguous 1-mm slices in the axial plane, starting with the distal end of the femur, and another block of 30 beginning with the proximal end of the tibia. The metric used was the median change from baseline to 4.5 months and 9 months, respectively. Higher values indicate improved bone trabeculae. | Four participants with motor complete spinal cord injury (C8-T10) ( 3 in the NMES + vit DArm and 1 in the Passive movement + Vit.D Arm) underwent MRI at 9 months. | Posted | Median | Inter-Quartile Range | um | 9 months |
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| Primary | Change in Trabecular Network Area Density (Tb.NA) Measured in mm^2/mm^3) at 4.5 Months | The outcome measure was trabecular network area density expressed in mm^2/mm^3, as measured by a non-contrast magnetic resonance imaging (MRI) of the femur and tibia. The metric used was the median change from baseline to 4.5 months and 9 months, respectively. Higher values indicate improved bone trabeculae network area density. A trained radiology technician performed the MRI using a 3.0T magnet (GE Discovery MR750 software, version: DV24 System 804675VA3T; GE Waukesha, WI). A specific knee coil with a 3D fast-spin gradient echo (10 min) sequence was used to obtain high-resolution images (20-22 FOV). A bilateral phased array coil (USA Instruments) was used to collect 30 contiguous 1-mm slices in the axial plane, starting with the distal end of the femur, and another block of 30 starting with the proximal end of the tibia. | All participants (n = 6) with chronic motor-complete spinal cord injury (C8-T10) and ASIA impairment classification of A or B completed an MRI at baseline and at 4.5 months. By 9 months, only four participants (n = 3 in the NMES + Vit. D group and n = 1 in the Passive movement + Vit. D group) completed the MRI after two participants (one in each group) voluntarily withdrew. | Posted | Median | Inter-Quartile Range | mm^2/mm^3 | 4.5 months |
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| Primary | Change in Trabecular Network Area Density (Tb.NA) as Measured by MRI at 9 Months | The outcome measure was trabecular network area density expressed in mm^2/mm^3, as measured by a non-contrast magnetic resonance imaging (MRI) of the femur and tibia. The metric used was the median change from baseline to 4.5 months and 9 months, respectively. Higher values indicate improved bone trabeculae network area density. A trained radiology technician performed the MRI using a 3.0T magnet (GE Discovery MR750 software, version: DV24 System 804675VA3T; GE Waukesha, WI). A specific knee coil with a 3D fast-spin gradient echo (10 min) sequence was used to obtain high-resolution images (20-22 FOV). A bilateral phased array coil (USA Instruments) was used to collect 30 contiguous 1-mm slices in the axial plane, starting with the distal end of the femur, and another block of 30 starting with the proximal end of the tibia. | Four participants with motor complete spinal cord injury (C8-T10), underwent MRI of both knees upon completion of the trial. | Posted | Median | Inter-Quartile Range | mm^2/mm^3 | 9 months |
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| Secondary | Change in Bone Mineral Density in Distal Femur as Measured by Dual Energy X-ray Absorptiometry (DXA) Scan | A dual-energy X-ray absorptiometry scan was performed by a trained technologist using a General Electric iDXA scanner (GE Lunar Inc., Madison, WI) at baseline, 4.5 months, and at 9 months. The scanner was calibrated using a phantom calibration box that mimics human tissues to assess scan precision and reliability. All participants had their jewelry removed before being placed supine on the scanning table with their arms internally rotated and palms facing medially. Participants received scans in the region of interest on both sides (L & R) of the body (hip, knee), as well as the lumbar spine. | Six males with motor complete spinal cord injury (C8-T10) underwent DXA scans after 4.5 months in the trial. | Posted | Median | Inter-Quartile Range | g/cm2 | 4.5 months |
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| Secondary | Change in Distal Femur Bone Mineral Density | A dual-energy X-ray absorptiometry scan was performed by a trained technologist using a General Electric iDXA scanner (GE Lunar Inc., Madison, WI) at baseline, 4.5 months, and at 9 months. The scanner was calibrated using a phantom calibration box that mimics human tissues to assess scan precision and reliability. All participants had their jewelry removed before being placed supine on the scanning table with their arms internally rotated and palms facing medially. Participants received scans in the region of interest on both sides (L & R) of the body (hip, knee), as well as the lumbar spine. | Four males with motor complete spinal cord injury (C8-T10) underwent DXA scans upon completing the trial. | Posted | Median | Inter-Quartile Range | g/cm2 | 9 months |
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| Secondary | Change in Proximal Tibia Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA) Scan | A dual-energy X-ray absorptiometry scan was performed by a trained technologist using a General Electric iDXA scanner (GE Lunar Inc., Madison, WI) at baseline, 4.5 months, and at 9 months. The scanner was calibrated using a phantom calibration box that mimics human tissues to assess scan precision and reliability. All participants had their jewelry removed before being placed supine on the scanning table with their arms internally rotated and palms facing medially. Participants received scans in the region of interest on both sides (L & R) of the body (hip, knee), as well as the lumbar spine. | Four males with motor complete spinal cord injury (C1-T10) underwent DXA of the knees after 4.5 months of the trial. | Posted | Median | Inter-Quartile Range | gm/cm2 | 4.5 months |
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| Secondary | Change in Proximal Tibia Bone Mineral Density as Measured by a Dual-energy X-ray Absorptiometry (DXA) Scan | A dual-energy X-ray absorptiometry scan was performed by a trained technologist using a General Electric iDXA scanner (GE Lunar Inc., Madison, WI) at baseline, 4.5 months, and at 9 months. The scanner was calibrated using a phantom calibration box that mimics human tissues to assess scan precision and reliability. All participants had their jewelry removed before being placed supine on the scanning table with their arms internally rotated and palms facing medially. Participants received scans in the region of interest on both sides (L & R) of the body (hip, knee), as well as the lumbar spine. | Four males with motor complete spinal cord injury (C8-T10) underwent DXA scan of the knees after 9 months of the trial. | Posted | Median | Inter-Quartile Range | gm/cm2 | 9 months |
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| Secondary | Change in Bone Formation Marker - Procollagen Type 1 N-terminal Propeptide (P1NP) in mcg/L | Fasting blood samples were collected by venipuncture by the same individual at roughly the same time of day and under similar conditions to evaluate P1NP, a marker of bone formation. Samples were analyzed at Quest Diagnostics (Nichols Institute, Chantilly, VA). The reference range for P1NP is 30-110 mcg/L, and an increase indicates poor bone health. | Six males with motor complete spinal cord injury (C8-T10). | Posted | Median | Inter-Quartile Range | mcg/L | 4.5 months |
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| Secondary | Change in Bone Formation Marker - Procollagen Type 1 Intact N-Propeptide (P1NP) Measured in mcg/L | Fasting blood samples were collected by venipuncture by the same individual at roughly the same time of day and under similar conditions to evaluate P1NP, a marker of bone formation. Samples were analyzed at Quest Diagnostics (Nichols Institute, Chantilly, VA). The reference range for P1NP is 30-110 mcg/L, and an increase indicates poor bone health. | Four males with motor complete spinal cord injury (C8-T10) | Posted | Median | Inter-Quartile Range | mcg/L | 9 months |
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| Secondary | Change in Bone Resorption Marker-C-telopeptide of Type I Collagen (CTX) | CTX is a biochemical marker of bone resorption. Fasting blood samples were collected from participants via venipuncture by the same person at approximately the same time of day and under similar conditions to measure CTX (pg/mL). The samples were analyzed by Quest Diagnostics (Nichols Institute, Chantilly, VA). Sex and age-related reference ranges for males are: 18-29 years (87-1200), 30-39 years (70-780), 40-49 years (60-700), and 50-68 years (87-345). CTX is released into circulation when osteoclasts break down bone matrix; therefore, higher levels indicate increased osteoclastic activity and faster bone turnover. | Six males with motor complete spinal cord injury (C8-T10) | Posted | Median | Inter-Quartile Range | pg/mL | 4.5 months |
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| Secondary | Change in Bone Resorption Marker-C-telopeptide of Type I Collagen (CTX) | CTX is a biochemical marker of bone resorption. Fasting blood samples were collected from participants via venipuncture by the same person at approximately the same time of day and under similar conditions to measure CTX (pg/mL). The samples were analyzed by Quest Diagnostics (Nichols Institute, Chantilly, VA). Sex and age-related reference ranges for males are as follows: 18-29 years (87-1200), 30-39 years (70-780), 40-49 years (60-700), and 50-68 years (87-345). CTX is released into circulation when osteoclasts break down bone matrix; therefore, higher levels indicate increased osteoclastic activity and faster bone turnover. | Four males with motor complete spinal cord injury (C8-T10). | Posted | Median | Inter-Quartile Range | pg/mL | 9 months |
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| Secondary | Change in Serum 25-hydroxyvitamin D [25(OD)D] Level | 25-hydroxyvitamin D is the major circulating form of vitamin D and the most reliable biochemical indicator of an individual's vitamin D status. It is essential for maintaining bone strength, balance of minerals, and overall bone integrity. Adequate levels of 25(OH)D enhance intestinal calcium absorption for normal bone formation and remodeling. When vitamin D levels are low, calcium absorption decreases, leading to secondary hyperparathyroidism, which in turn increases bone resorption and weakens bone structure. The normal range is 32 to 100 ng/mL. Less than 20ng/mL is considered a deficiency, and 20 to 29 ng/mL is insufficiency. | Six males with motor complete spinal cord injury (C8-T10). | Posted | Median | Inter-Quartile Range | ng/mL | 4.5 months |
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| Secondary | Change in Serum 25-hydroxyvitamin D Level | 25-hydroxyvitamin D is the main circulating form of vitamin D and the most reliable biochemical marker of an individual's vitamin D status. Vitamin D is crucial for maintaining bone strength, mineral balance, and overall bone health. Adequate levels of 25(OH)D improve intestinal calcium absorption, which is vital for normal bone formation and remodeling. When vitamin D levels are low, calcium absorption drops, leading to secondary hyperparathyroidism, which then increases bone resorption and weakens bone structure. The normal range is 32 to 100 ng/mL. Less than 20 ng/mL is considered a deficiency, and 20 to 29 ng/mL indicates insufficiency. | Four males with motor complete spinal cord injury (C8 to T10) | Posted | Median | Inter-Quartile Range | ng/mL | 9 months |
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| Secondary | Change in Quality-of-life Measure: Physical Health (Scored on 1-5 Likert Scale) | The secondary outcome measure was the WHO Quality of Life (WHOQOL)-BREF, a 26-item self-administered questionnaire developed by WHO to assess quality of life across four domains, including two general items. Each item is rated on a 5-point Likert scale (1 = negative or low perception, 5 = positive or high perception). The instrument includes four health domains: physical health, psychological health, social relationships, and environmental engagement. Physical health (7 items) evaluates energy, fatigue, sleep, mobility, pain, and activities of daily living. The maximum score for this domain is 100, and a higher score indicates a better quality of life. | Four males with chronic motor-complete spinal cord injury (C8-T10). | Posted | Median | Inter-Quartile Range | units on a scale (0-100) | 9 months |
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| Secondary | Change in Quality-of-life Measure- Psychological Health | The WHOQOL-BREF instrument was used to assess QOL in four domains of health, including: physical health, psychological health, social relationships, and environmental engagement. The mean scores of items within each domain were used to calculate domain scores, which were then transformed using the WHOQOL-BREF scoring manual to make the domain scores comparable to those used in the WHOQOL-100. Items 3, 4, and 26 were reverse-coded per the instruction manual. Psychological health (6 items) measures self-esteem, body image, negative and positive feelings, and concentration. A higher score denotes higher psychological health. | Six males with motor-complete spinal cord injury (C8-T10) | Posted | Median | Inter-Quartile Range | score on a scale (0-100) | 9 months |
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| Secondary | Change in Quality-of-life Measure- Social Relationships Domain | The WHOQOL-BREF instrument was used to assess QOL in four domains of health, including: physical health, psychological health, social relationships, and environment. The mean scores of items within each domain were used to calculate domain scores, which were then transformed using the WHOQOL-BREF scoring manual to make the domain scores comparable to those used in the WHOQOL-100. Items 3, 4, and 26 were reverse-coded per the instruction manual. Social relationships (3 items) assess personal relationships, social support, and sexual life. A higher score denotes a higher social relationships. | Six males with motor-complete spinal cord injury (C8-T10). | Posted | Median | Inter-Quartile Range | score on a scale (0-100) | 9 months |
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| Secondary | Change in Quality-of-life Measure-environmental Engagement Domain | The WHOQOL-BREF instrument was used to assess QOL in four domains of health participants, including: physical health, psychological health, social relationships, and environmental engagement. The mean scores of items within each domain were used to calculate domain scores, which were then transformed using the WHOQOL-BREF scoring manual to make the domain scores comparable to those used in the WHOQOL-100. Items 3, 4, and 26 were reverse-coded per the instruction manual. Environmental engagement (8 items) assesses financial resources, safety, home environment, health care access, and opportunities for recreation and learning. A Higher score denotes better environmental engagement. | Four males with motor complete spinal cord injury (C8 to T10). | Posted | Median | Inter-Quartile Range | units on a scale (0-100) | 9 months |
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| EG001 | Passive Movement Plus Vitamin D | Subjects will undergo 9 months of simple passive movement exercise at home and 2000IU oral vitamin D supplementation daily for 9 months. Vitamin D: 2000IU oral vitamin D supplementation daily for 9 months Passive movement: Subjects will perform simple passive movement exercise for their legs while sitting in their wheelchairs at their home. The frequency of the training will be twice weekly. . | 0 | 2 | 0 | 2 | 0 | 2 |
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| D014947 | Wounds and Injuries |
| D011083 |
| Polycyclic Compounds |
| D010808 | Physical Examination |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D009142 | Musculoskeletal Physiological Phenomena |
| D055687 | Musculoskeletal and Neural Physiological Phenomena |