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| Name | Class |
|---|---|
| Tulane University Health Sciences Center | OTHER |
| VA Nebraska Western Iowa Health Care System | FED |
| Scott and White Hospital & Clinic | OTHER |
| Dallas Diabetes and Endocrine Center |
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The purpose of this research study is to determine if Metanx improves sensory neuropathy in persons with Type 2 diabetes. Metanx is a medical food available with a prescription from a physician. It consists of L-methylfolate, Pyridoxal 5'-phosphate, and Methylcobalamin, which are the active forms of folate, vitamin B6, and vitamin B12, respectively. Subjects will be randomly assigned to receive either Metanx or placebo for 6 months.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1 | Experimental | Metanx |
|
| 2 | Placebo Comparator | Placebo |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Metanx (a medical food) | Other | Metanx one tablet twice a day |
| |
| Metanx placebo |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Vibration Perception Threshold (VPT) at 24 Weeks | Vibration Perception Threshold (VPT) 25-45 volts at hallux on either leg as measured by VPT meter on the great toe of each foot. Mean VPT averaged across both toes. | VPT was measured a 0 (baseline), and 24 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Neuropathy Total Symptom Score-6 (NTSS-6) | This measure was taken to determine if Metanx® (compared to placebo) changes neuropathic symptoms as evaluated by the Neuropathy Total Symptom Score-6 (NTSS-6) The Neuropathy Total Symptom Score-6 Scale (NTSS-6) is a validated scale that evaluates individual neuropathy sensory symptoms in patients with diabetes mellitus (DM) and diabetic peripheral neuropathy (DPN). This scale was a modified 6 item scale that consists of yes or no questions. Scores range between 0 and 21.96, a higher score indicates greater severity of symptoms. After adjusting for baseline measurements scores are reflected as negative numbers. Negative numbers indicate improvement in symptoms. ie. a change from baseline after 24 weeks of -2 would be a greater improvement than a change in baseline of -1 after 24 weeks. |
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Inclusion Criteria:
Male or female between 25 and 80 years of age (inclusive);
Documented diabetes mellitus Type 2 (Based upon ADA criteria);
Peripheral polyneuropathy: Vibration Perception Threshold (VPT) 25-45 Volts at hallux on either leg.
Adequate lower extremity vascular status:
The subject is able to understand the information in the informed consent form and is willing and able to sign the consent.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Vivian Fonseca, MD | Tulane University Health Sciences Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Alabama at Birmingham School of Medicine | Birmingham | Alabama | 35294 | United States | ||
| Tulane University Health Sciences Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23218892 | Result | Fonseca VA, Lavery LA, Thethi TK, Daoud Y, DeSouza C, Ovalle F, Denham DS, Bottiglieri T, Sheehan P, Rosenstock J. Metanx in type 2 diabetes with peripheral neuropathy: a randomized trial. Am J Med. 2013 Feb;126(2):141-9. doi: 10.1016/j.amjmed.2012.06.022. Epub 2012 Dec 5. |
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Inclusion criteria included individuals 25 and 80 years of age, documented diabetes Type 2, Peripheral polyneuropathy, adequate lower extremity vascular status, and subject competence. 17 exclusion criteria including an HbA1c >9, uncontrolled heart or lung disease, and vitamin B supplementation, contributed to the number of screening failures.
Of 373 patients screened, 214 entered the study , and 200 completed. The study was conducted at 6 participating U.S. sites
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| ID | Title | Description |
|---|---|---|
| FG000 | Metanx | Patients aged 25 to 80 years with type 2 diabetes and neuropathy, were given Metanx (L-methylfolate calcium 3 mg, methylcobalamin 2 mg, and pyridoxal-5'-phosphate 35 mg (LMF-MC-PLP)) one tablet twice a day. |
| FG001 | Placebo | Patients aged 25 to 80 years with type 2 diabetes and neuropathy, were given Placebo, one tablet twice a day |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Metanx | Metanx one tablet twice a day |
| BG001 | Placebo | Placebo one tablet twice a day |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age Continuous | Mean |
| 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 From Baseline in Vibration Perception Threshold (VPT) at 24 Weeks | Vibration Perception Threshold (VPT) 25-45 volts at hallux on either leg as measured by VPT meter on the great toe of each foot. Mean VPT averaged across both toes. | Posted | Mean | Standard Deviation | volts | VPT was measured a 0 (baseline), and 24 weeks |
|
Reported Adverse Events (AEs) included events starting on or after the baseline visit until 4 weeks after the last study visit on week 24. The total duration of AE monitoring was 196 days.
An adverse event is any undesirable sign, symptom or medical condition occurring after starting study drug, even if the event is not considered to be related to study drug.
Adverse Event reporting was provided only with specificity to the affected Organ System. Additional detail was not available at the time of reporting.
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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 | Metanx | Metanx one tablet twice a day |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Transient Ischemic Attack | Vascular disorders | MedDRA 13.1 | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Infections and infestations | Infections and infestations | MedDRA 13.1 | Non-systematic Assessment |
Adverse Event reporting detailed in the "Other Adverse Events" section was provided only with specificity to the affected Organ System. Additional detail for the "Other Adverse Events" was not available at the time of reporting.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Page Young, Clinical Project Manager | Pamlab Inc. | 985-867-5788 | pyoung@pamlab.com |
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| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| ID | Term |
|---|---|
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
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| ID | Term |
|---|---|
| C575384 | metanx |
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| OTHER |
| University of Alabama at Birmingham | OTHER |
| dgd Research, Inc. | INDUSTRY |
| Baylor Health Care System | OTHER |
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| Other |
Metanx placebo one tablet twice a day |
|
| NTSS-6 scores were taken at 0 (Baseline), 16, and 24 weeks |
| Change From Baseline in Neuropathy Disability Score (NDS)at Week 16 and 24 | This outcome was taken to determine if Metanx® (compared to placebo) has an effect on clinical examination as determined by the Neuropathy Disability Score (NDS) The Neuropathy Disability Score (NDS) evaluates the severity of individual symptoms of neuropathy. A simple visual numeric distress scale is used that ranges from 0 to 10. The most favorable score is 0, which indicates an absence of symptoms. The most severe symptoms possible would be recorded as a score of 10. | NDS scores were taken at 0 (Baseline), 16, and 24 weeks |
| Change From Baseline in Plasma Marker Levels of Total Folate and Total Methyl Malonic Acid (MMA) at Week 16 and 24 | To determine if Metanx® (compared to placebo) affects a change in subject's total folate and total methyl malonic acid (MMA) at week 16 and 24 | Change from Baseline in Plasma Marker Levels at 0 (Baseline), 16, and 24 weeks |
| Change From Baseline in SF-36 MCS and SF-36 PCS at Week 24 | To determine if Metanx® (compared to placebo) affects a subject's "quality of life" as determined by the SF-36 questionnaire The Short Form- 36 Mental Component Summary (SF-36 MCS) and SF-36 Physical Component Summary (SF-36 PCS) both measure health related quality of life, the MCS quantifying mental health and the PCS quantifying physical function. They are both scored on 100 point scales with 0 representing the worst possible outcome and 100 representing the most optimal possible scoring | SF-36 MCS and SF-36 PCS scores were measured at 0 (Baseline) and 24 weeks |
| Change From Baseline in 10-point Visual Analog Scale(VAS) at Week 24 | To determine if Metanx® (compared to placebo) affects a subject's lower extremity pain level using a 10-point Visual Analog Scale at Baseline and 24-week evaluation visits. The Visual Analog Scale (VAS) measures a patients sensation of pain. A 10-cm visual analog scale is used. A measurement on the 10 cm analog scale is used to quantify the level of pain indicated with 0 cm indicating "no pain" and 10 cm indicating the "worst pain imaginable". | VAS scores were taken at 0 (Baseline) and 24 weeks |
| (Exploratory) Change From Baseline in Levels of IL-6 and TNF-α, at Week 24 | (Exploratory) To determine if Metanx® affects a subject's plasma oxidative stress and inflammatory marker levels, including IL-6 and TNF-α | Analyte levels were taken at 0 (Baseline) and 24 weeks |
| (Exploratory) Change From Baseline in the Hospital Anxiety and Depression Scale (HADS) Question Inventory at Week 24 | The Hospital Anxiety and Depression Scale (HADS) consists of a 14-item questionnaire that provides a measurement of depression. Each item is rated on a 4-point scale, giving a maximum scores of 21 for the most severe depression. Depression was evaluated using the Hospital Anxiety and Depression Scale (HADS) question inventory at Baseline, and 24-week evaluation visits | HADS Scores scores were taken at 0 (Baseline) and 24 weeks |
| Change From Baseline in Total Homocysteine at Week 16 and 24 | To determine if Metanx® (compared to placebo) affects change in subjects total homocysteine levels | Change from Baseline in Plasma Marker Levels at 0 (Baseline), 16, and 24 weeks |
| (Exploratory) Change From Baseline in Levels of Hs-CRP at Week 24 | (Exploratory) To determine if Metanx® affects a subject's plasma oxidative stress and inflammatory markers levels including hs-CRP | Analyte levels were taken at 0 (Baseline) and 24 weeks |
| (Exploratory) Change From Baseline in Levels Potential Antioxidant (PAO) at Week 24 | (Exploratory) To determine if Metanx® affects a subject's plasma oxidative stress and inflammatory markers levels including Potential Antioxidant (PAO) | Analyte levels were taken at 0 (Baseline) and 24 weeks |
| New Orleans |
| Louisiana |
| 70112 |
| United States |
| Omaha VA Medical Center | Omaha | Nebraska | 68105 | United States |
| Dallas Diabetes and Endocrine Center | Dallas | Texas | 75230 | United States |
| dgd Research, Inc. | San Antonio | Texas | 78229 | United States |
| Scott and White Hospital & Clinic | Temple | Texas | 76504 | United States |
| BG002 |
| Total |
Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
|
|
| Secondary | Change From Baseline in Neuropathy Total Symptom Score-6 (NTSS-6) | This measure was taken to determine if Metanx® (compared to placebo) changes neuropathic symptoms as evaluated by the Neuropathy Total Symptom Score-6 (NTSS-6) The Neuropathy Total Symptom Score-6 Scale (NTSS-6) is a validated scale that evaluates individual neuropathy sensory symptoms in patients with diabetes mellitus (DM) and diabetic peripheral neuropathy (DPN). This scale was a modified 6 item scale that consists of yes or no questions. Scores range between 0 and 21.96, a higher score indicates greater severity of symptoms. After adjusting for baseline measurements scores are reflected as negative numbers. Negative numbers indicate improvement in symptoms. ie. a change from baseline after 24 weeks of -2 would be a greater improvement than a change in baseline of -1 after 24 weeks. | Posted | Mean | Standard Deviation | units on a scale (0-6) | NTSS-6 scores were taken at 0 (Baseline), 16, and 24 weeks |
|
|
|
|
| Secondary | Change From Baseline in Neuropathy Disability Score (NDS)at Week 16 and 24 | This outcome was taken to determine if Metanx® (compared to placebo) has an effect on clinical examination as determined by the Neuropathy Disability Score (NDS) The Neuropathy Disability Score (NDS) evaluates the severity of individual symptoms of neuropathy. A simple visual numeric distress scale is used that ranges from 0 to 10. The most favorable score is 0, which indicates an absence of symptoms. The most severe symptoms possible would be recorded as a score of 10. | Posted | Mean | Standard Deviation | units on a scale (0-10) | NDS scores were taken at 0 (Baseline), 16, and 24 weeks |
|
|
|
|
| Secondary | Change From Baseline in Plasma Marker Levels of Total Folate and Total Methyl Malonic Acid (MMA) at Week 16 and 24 | To determine if Metanx® (compared to placebo) affects a change in subject's total folate and total methyl malonic acid (MMA) at week 16 and 24 | Posted | Mean | Standard Deviation | nmol/L | Change from Baseline in Plasma Marker Levels at 0 (Baseline), 16, and 24 weeks |
|
|
|
|
| Secondary | Change From Baseline in SF-36 MCS and SF-36 PCS at Week 24 | To determine if Metanx® (compared to placebo) affects a subject's "quality of life" as determined by the SF-36 questionnaire The Short Form- 36 Mental Component Summary (SF-36 MCS) and SF-36 Physical Component Summary (SF-36 PCS) both measure health related quality of life, the MCS quantifying mental health and the PCS quantifying physical function. They are both scored on 100 point scales with 0 representing the worst possible outcome and 100 representing the most optimal possible scoring | Posted | Mean | Standard Deviation | units on a scale (0-100) | SF-36 MCS and SF-36 PCS scores were measured at 0 (Baseline) and 24 weeks |
|
|
|
|
| Secondary | Change From Baseline in 10-point Visual Analog Scale(VAS) at Week 24 | To determine if Metanx® (compared to placebo) affects a subject's lower extremity pain level using a 10-point Visual Analog Scale at Baseline and 24-week evaluation visits. The Visual Analog Scale (VAS) measures a patients sensation of pain. A 10-cm visual analog scale is used. A measurement on the 10 cm analog scale is used to quantify the level of pain indicated with 0 cm indicating "no pain" and 10 cm indicating the "worst pain imaginable". | Posted | Mean | Standard Deviation | units on a scale (0-10) | VAS scores were taken at 0 (Baseline) and 24 weeks |
|
|
|
| Secondary | (Exploratory) Change From Baseline in Levels of IL-6 and TNF-α, at Week 24 | (Exploratory) To determine if Metanx® affects a subject's plasma oxidative stress and inflammatory marker levels, including IL-6 and TNF-α | Posted | Mean | Standard Deviation | pg/mL | Analyte levels were taken at 0 (Baseline) and 24 weeks |
|
|
|
| Secondary | (Exploratory) Change From Baseline in the Hospital Anxiety and Depression Scale (HADS) Question Inventory at Week 24 | The Hospital Anxiety and Depression Scale (HADS) consists of a 14-item questionnaire that provides a measurement of depression. Each item is rated on a 4-point scale, giving a maximum scores of 21 for the most severe depression. Depression was evaluated using the Hospital Anxiety and Depression Scale (HADS) question inventory at Baseline, and 24-week evaluation visits | Posted | Mean | Standard Deviation | units on a scale (0-21) | HADS Scores scores were taken at 0 (Baseline) and 24 weeks |
|
|
|
|
| Secondary | Change From Baseline in Total Homocysteine at Week 16 and 24 | To determine if Metanx® (compared to placebo) affects change in subjects total homocysteine levels | Posted | Mean | Standard Deviation | µmol/L | Change from Baseline in Plasma Marker Levels at 0 (Baseline), 16, and 24 weeks |
|
|
|
| Secondary | (Exploratory) Change From Baseline in Levels of Hs-CRP at Week 24 | (Exploratory) To determine if Metanx® affects a subject's plasma oxidative stress and inflammatory markers levels including hs-CRP | Posted | Mean | Standard Deviation | mg/L | Analyte levels were taken at 0 (Baseline) and 24 weeks |
|
|
|
| Secondary | (Exploratory) Change From Baseline in Levels Potential Antioxidant (PAO) at Week 24 | (Exploratory) To determine if Metanx® affects a subject's plasma oxidative stress and inflammatory markers levels including Potential Antioxidant (PAO) | Posted | Mean | Standard Deviation | µmol/L | Analyte levels were taken at 0 (Baseline) and 24 weeks |
|
|
|
| 5 |
| 106 |
| 25 |
| 106 |
| EG001 | Placebo | Placebo one tablet twice a day | 8 | 108 | 27 | 108 |
| Knee arthroplasty | Surgical and medical procedures | MedDRA 13.1 | Non-systematic Assessment |
|
| Ligament Operation | Surgical and medical procedures | MedDRA 13.1 | Non-systematic Assessment |
|
| Breast Cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 13.1 | Non-systematic Assessment |
|
| Coronary Artery Bypass | Surgical and medical procedures | MedDRA 13.1 | Non-systematic Assessment |
|
| Death | General disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Pancreatitis | Gastrointestinal disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Chest Pain | General disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Cardiac Failure, Congestive | Cardiac disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Injury, poisoning, and procedural complications | Injury, poisoning and procedural complications | MedDRA 13.1 | Non-systematic Assessment |
|
| General disorders and administration site conditions | General disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Musculoskeletal and connective tissue disorders | Musculoskeletal and connective tissue disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Skin and subcutaneous tissue disorders | Skin and subcutaneous tissue disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Surgical and medical procedures | Surgical and medical procedures | MedDRA 13.1 | Non-systematic Assessment |
|
| Gastrointestinal disorders | Gastrointestinal disorders | MedDRA 13.1 | Non-systematic Assessment |
|
| Metabolism and nutrition disorders | Metabolism and nutrition disorders | MedDRA 13.1 | Non-systematic Assessment |
|
Investigators agreed to delay publication of study results until after multi-center results were published or, a period of up to 20 months had elapsed after termination of the study, whichever shall occur first.
| Change from Baseline Week 24 |
|
| Mixed Models Analysis |
Generalized linear mixed models were used to assess baseline for continuous and discrete outcomes |
| =0.033 |
| No |
| Superiority or Other |
| Change from Baseline Week 24 |
|
| Total Folate, Change from BL Week 24 |
|
| Total methyl malonic acid (MMA) (nmol/L) at BL |
|
| Total MMA, Change from BL Week 16 |
|
| Total MMA, Change from BL Week 24 |
|
| Mixed Models Analysis |
| =0.0001 |
Generalized linear mixed models were used to assess baseline for continuous and discrete outcomes |
| No |
| Superiority or Other |
| Total MMA, Change from Baseline Week 16 | Mixed Models Analysis | Generalized linear mixed models were used to assess baseline for continuous and discrete outcomes | =0.0001 | No | Superiority or Other |
| Total MMA, Change from BL, Week 24 | Mixed Models Analysis | Generalized linear mixed models were used to assess baseline for continuous and discrete outcomes | =0.0008 | No | Superiority or Other |
| Total Homocysteine, Change from BL, Week 16 | Mixed Models Analysis | =0.0001 | Generalized linear mixed models were used to assess baseline for continuous and discrete outcomes | No | Superiority or Other |
| Total Homocysteine, Change from BL, Week 24 | Mixed Models Analysis | Generalized linear mixed models were used to assess baseline for continuous and discrete outcomes | =0.0001 | No | Superiority or Other |
| SF-36 MCS, Baseline |
|
| SF-36 MCS, Change from BL, Week 24 |
|
| TNF-a (pg/mL), Baseline |
|
| TNF-a, Change from BL, Week 24 |
|
| Total homocysteine, Change from BL Week 24 |
|