Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| The Glass Foundation | UNKNOWN |
Not provided
Not provided
Not provided
Purpose of the study: Patients with mild Alzheimer's Disease will be given three different drugs over a 4-month period to try to increase the blood flow to their brains, and improve blood vessel and brain function. Each drug can help to open the blood vessels in the brain, and together they may be more effective than each drug alone. The hypothesis is that small blood vessels secrete substances that maintain the integrity of the brain, and may prevent loss of nerve cells leading to Alzheimer's Disease
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Simvastatin + L-Arginine + Tetrahydrobiopterin | Experimental | Simvastatin, 40 mg per day orally; L-Arginine, 2 Gm four times per day orally; Tetrahydrobiopterin 20 mg/kg/day orally |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Simvastatin | Drug | Simvastatin, 40 mg per day orally |
|
| Measure | Description | Time Frame |
|---|---|---|
| Mean Change in Cerebral Blood Flow as Measured by Magnetic Resonance Imaging (MRI) | Measurement of changes to cerebral blood flow (ml/110g/min) in regions of interest as measured using Magnetic Resonance Imaging (MRI) | Baseline to 16 weeks |
| Change in Cerebral Blood Flow as Measured by Arterial Spin Labeling During Magnetic Resonance Imaging (MRI) | Data not available as files corrupted and could not be analyzed | Baseline to week 16 |
| Measure | Description | Time Frame |
|---|---|---|
| Mini Mental State Examination (MMSE) Scores | Change in mental state as reflected by changes to mean Mini Mental State Examination (MMSE) score as measured 4 weeks, 8 weeks and 16 weeks post-baseline. The MMSE uses a 30 point questionnaire to measure cognitive impairment. The MMSE is scored from 0 to 30,with a score equal to or greater than 24 points indicating normal cognition, a score of 19-23 points indicating mild cognitive impairment, 10-18 points indicating moderate impairment and a score equal to or below 9 indicating severe impairment. |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Elizabeth R DeGrush, DO | UMass Medical School | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UMass Medical School/ UMass Memorial Medical Center | Worcester | Massachusetts | 01655 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36115980 | Derived | Degrush E, Shazeeb MS, Drachman D, Vardar Z, Lindsay C, Gounis MJ, Henninger N. Cumulative effect of simvastatin, L-arginine, and tetrahydrobiopterin on cerebral blood flow and cognitive function in Alzheimer's disease. Alzheimers Res Ther. 2022 Sep 17;14(1):134. doi: 10.1186/s13195-022-01076-7. |
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Simvastatin + L-Arginine + Tetrahydrobiopterin | Simvastatin, 40 mg per day orally; L-Arginine, 2 Gm four times per day orally; Tetrahydrobiopterin 20 mg/kg/day orally Simvastatin: Simvastatin, 40 mg per day orally L-Arginine: L-Arginine, 2 Gm four times per day orally; Tetrahydrobiopterin: Tetrahydrobiopterin 20 mg/kg/day orally |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Prospective, open-label, single group assignment, single center study conducted by UMass Medical School at the UMass Memorial Medical Center in Worcester, MA. 11 subjects total were screened and enrolled in this study, 10 subjects completed the study as 1 subject was initially enrolled but was excluded due to not meeting inclusion criteria.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Simvastatin + L-Arginine + Tetrahydrobiopterin | Simvastatin, 40 mg per day orally; L-Arginine, 2 Gm four times per day orally; Tetrahydrobiopterin 20 mg/kg/day orally Simvastatin: Simvastatin, 40 mg per day orally L-Arginine: L-Arginine, 2 Gm four times per day orally; Tetrahydrobiopterin: Tetrahydrobiopterin 20 mg/kg/day orally |
| 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 | Mean Change in Cerebral Blood Flow as Measured by Magnetic Resonance Imaging (MRI) | Measurement of changes to cerebral blood flow (ml/110g/min) in regions of interest as measured using Magnetic Resonance Imaging (MRI) | Data for 6 participants available. Data file for remaining participants corrupted and could not be retrieved for analysis/reporting. | Posted | Mean | Standard Deviation | ml/110g/min | Baseline to 16 weeks |
|
6 Years.
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Simvastatin + L-Arginine + Tetrahydrobiopterin | Simvastatin, 40 mg per day orally; L-Arginine, 2 Gm four times per day orally; Tetrahydrobiopterin 20 mg/kg/day orally Simvastatin: Simvastatin, 40 mg per day orally L-Arginine: L-Arginine, 2 Gm four times per day orally; Tetrahydrobiopterin: Tetrahydrobiopterin 20 mg/kg/day orally |
Not provided
Not provided
The data for the MRI measurements (cerebral blood flow) experienced file corruption, rendering segments of data irretrievable and the whole set non-analyzable.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Elizabeth DeGrush, DO | UMass Medical School | 508-334-1000 | elizabeth.degrush@umassmemorial.org |
Not provided
| 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 11, 2017 | Mar 18, 2019 | Prot_SAP_000.pdf |
Not provided
| ID | Term |
|---|---|
| D000544 | Alzheimer Disease |
| D060825 | Cognitive Dysfunction |
| ID | Term |
|---|---|
| D003704 | Dementia |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D019821 | Simvastatin |
| C003402 | sapropterin |
| D001120 | Arginine |
| ID | Term |
|---|---|
| D008148 | Lovastatin |
| D009281 | Naphthalenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| L-Arginine | Drug | L-Arginine, 2 Gm four times per day orally; |
|
| Tetrahydrobiopterin | Drug | Tetrahydrobiopterin 20 mg/kg/day orally |
|
|
| Baseline to 4 weeks, 8 weeks and 16 weeks post-baseline |
| Cognitive Assessment Screening Test (CAST) | This outcome measured the change in average Cognitive Assessment Screening Test (CAST) scores for the participant group. The CAST is scored from 0 to 40. A higher score indicates better performance, and a lower score indicates worse performance. The participants were given the CAST at baseline, 4 weeks, 8 weeks and 16 weeks post-baseline. The outcome reports on the averaged change for the averaged CAST scores from baseline to 16 weeks. | Baseline to 16 weeks post-baseline |
| Clinical Dementia Rating Scale (CDR) | This outcome measures Clinical Dementia Rating Scale (CDR) scores at baseline (enrollment) and 16 weeks post-enrollment. The Clinical Dementia Rating Scale is scored with a composite scale of 0 to 3, with higher scores indicating lower functional status and lower scores indicating better functional status. | Baseline to 16 weeks post-baseline |
| Alzheimer's Disease Assessment Scale: Cognitive and Modified Version (ADAS-COG) | Mean Alzheimer's Disease Assessment Scale: Cognitive Subscale (ADAS-COG) score at baseline and at 16 weeks post-enrollment. The ADAS-COG consists of 11 tasks measuring disturbances of memory, language, praxis, attention and other cognitive abilities. Total scores range from 0 to 70, with higher scores (18 and above) indicating greater cognitive impairment. | Baseline to 16 weeks post-baseline |
| Clinical Interview Based Impression of Change + Caregiver Input (CIBIC Plus) | The Clinical Interview Based Impression of Change + Caregiver Input (CIBIC Plus) is a semi-structured instrument to examine four major areas of patient function: General, Cognitive, Behavioral and Activities of Daily Living. It is scored from 1 to 7. A score of 1 indicates marked improvement, 4 indicates no change and 7 indicates marked worsening. | Baseline to 4 weeks, 8 weeks and 16 weeks post-baseline |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | Years of Age |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Units | Counts |
|---|---|
| Participants |
|
|
| Primary | Change in Cerebral Blood Flow as Measured by Arterial Spin Labeling During Magnetic Resonance Imaging (MRI) | Data not available as files corrupted and could not be analyzed | Data files corrupted, analysis not possible | Posted | Baseline to week 16 |
|
|
| Secondary | Mini Mental State Examination (MMSE) Scores | Change in mental state as reflected by changes to mean Mini Mental State Examination (MMSE) score as measured 4 weeks, 8 weeks and 16 weeks post-baseline. The MMSE uses a 30 point questionnaire to measure cognitive impairment. The MMSE is scored from 0 to 30,with a score equal to or greater than 24 points indicating normal cognition, a score of 19-23 points indicating mild cognitive impairment, 10-18 points indicating moderate impairment and a score equal to or below 9 indicating severe impairment. | Patients were sequentially treated with the HMC-CoA reductase synthesis inhibitor simvastatin (weeks 0-16); L-Arginine (weeks 4-16); and tetrahydrobiopterin (weeks 8-16). The investigators assessed cognitive function with a psychometric battery including the MMSE at each time point. | Posted | Mean | Standard Deviation | score on a scale | Baseline to 4 weeks, 8 weeks and 16 weeks post-baseline |
|
|
|
| Secondary | Cognitive Assessment Screening Test (CAST) | This outcome measured the change in average Cognitive Assessment Screening Test (CAST) scores for the participant group. The CAST is scored from 0 to 40. A higher score indicates better performance, and a lower score indicates worse performance. The participants were given the CAST at baseline, 4 weeks, 8 weeks and 16 weeks post-baseline. The outcome reports on the averaged change for the averaged CAST scores from baseline to 16 weeks. | Posted | Mean | Standard Deviation | score on a scale | Baseline to 16 weeks post-baseline |
|
|
|
| Secondary | Clinical Dementia Rating Scale (CDR) | This outcome measures Clinical Dementia Rating Scale (CDR) scores at baseline (enrollment) and 16 weeks post-enrollment. The Clinical Dementia Rating Scale is scored with a composite scale of 0 to 3, with higher scores indicating lower functional status and lower scores indicating better functional status. | Posted | Mean | Standard Deviation | score on a scale | Baseline to 16 weeks post-baseline |
|
|
|
| Secondary | Alzheimer's Disease Assessment Scale: Cognitive and Modified Version (ADAS-COG) | Mean Alzheimer's Disease Assessment Scale: Cognitive Subscale (ADAS-COG) score at baseline and at 16 weeks post-enrollment. The ADAS-COG consists of 11 tasks measuring disturbances of memory, language, praxis, attention and other cognitive abilities. Total scores range from 0 to 70, with higher scores (18 and above) indicating greater cognitive impairment. | Posted | Mean | Standard Deviation | score on a scale | Baseline to 16 weeks post-baseline |
|
|
|
| Secondary | Clinical Interview Based Impression of Change + Caregiver Input (CIBIC Plus) | The Clinical Interview Based Impression of Change + Caregiver Input (CIBIC Plus) is a semi-structured instrument to examine four major areas of patient function: General, Cognitive, Behavioral and Activities of Daily Living. It is scored from 1 to 7. A score of 1 indicates marked improvement, 4 indicates no change and 7 indicates marked worsening. | Posted | Mean | Standard Deviation | score on a scale | Baseline to 4 weeks, 8 weeks and 16 weeks post-baseline |
|
|
|
| 0 |
| 10 |
| 0 |
| 10 |
| 0 |
| 10 |
Not provided
Not provided
Not provided
| D024801 |
| Tauopathies |
| D019636 | Neurodegenerative Diseases |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
| D003072 | Cognition Disorders |
| D006844 |
| Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D011083 | Polycyclic Compounds |
| D024361 | Amino Acids, Basic |
| D000596 | Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |
| D000599 | Amino Acids, Diamino |
| D000601 | Amino Acids, Essential |
| Title | Measurements |
|---|---|
|
| Week 16 |
|
|