Trial Outcomes & Findings for Endothelial Facilitation in Alzheimer's Disease (NCT NCT01439555)
NCT ID: NCT01439555
Last Updated: 2019-07-30
Results Overview
Measurement of changes to cerebral blood flow (ml/110g/min) in regions of interest as measured using Magnetic Resonance Imaging (MRI)
COMPLETED
PHASE2
11 participants
Baseline to 16 weeks
2019-07-30
Participant Flow
Participant milestones
| Measure |
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
|
|---|---|
|
Overall Study
STARTED
|
11
|
|
Overall Study
COMPLETED
|
10
|
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Overall Study
NOT COMPLETED
|
1
|
Reasons for withdrawal
| Measure |
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
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|---|---|
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Overall Study
Protocol Violation
|
1
|
Baseline Characteristics
Endothelial Facilitation in Alzheimer's Disease
Baseline characteristics by cohort
| Measure |
Simvastatin + L-Arginine + Tetrahydrobiopterin
n=10 Participants
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
|
|---|---|
|
Age, Categorical
<=18 years
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0 Participants
n=93 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
1 Participants
n=93 Participants
|
|
Age, Categorical
>=65 years
|
9 Participants
n=93 Participants
|
|
Age, Continuous
|
67.1 Years of Age
STANDARD_DEVIATION 6.84 • n=93 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=93 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=93 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
White
|
10 Participants
n=93 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
|
Region of Enrollment
United States
|
10 participants
n=93 Participants
|
PRIMARY outcome
Timeframe: Baseline to 16 weeksPopulation: Data for 6 participants available. Data file for remaining participants corrupted and could not be retrieved for analysis/reporting.
Measurement of changes to cerebral blood flow (ml/110g/min) in regions of interest as measured using Magnetic Resonance Imaging (MRI)
Outcome measures
| Measure |
Simvastatin + L-Arginine + Tetrahydrobiopterin
n=6 Participants
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
|
|---|---|
|
Mean Change in Cerebral Blood Flow as Measured by Magnetic Resonance Imaging (MRI)
Baseline
|
0.621528 ml/110g/min
Standard Deviation 0.116513988
|
|
Mean Change in Cerebral Blood Flow as Measured by Magnetic Resonance Imaging (MRI)
Week 4
|
0.6447692 ml/110g/min
Standard Deviation 0.070388324
|
|
Mean Change in Cerebral Blood Flow as Measured by Magnetic Resonance Imaging (MRI)
Week 8
|
0.654822667 ml/110g/min
Standard Deviation 0.024032403
|
|
Mean Change in Cerebral Blood Flow as Measured by Magnetic Resonance Imaging (MRI)
Week 16
|
0.579838667 ml/110g/min
Standard Deviation 0.091658076
|
PRIMARY outcome
Timeframe: Baseline to week 16Population: Data files corrupted, analysis not possible
Data not available as files corrupted and could not be analyzed
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline to 4 weeks, 8 weeks and 16 weeks post-baselinePopulation: 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.
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.
Outcome measures
| Measure |
Simvastatin + L-Arginine + Tetrahydrobiopterin
n=10 Participants
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
|
|---|---|
|
Mini Mental State Examination (MMSE) Scores
Baseline
|
24.2 score on a scale
Standard Deviation 3.155
|
|
Mini Mental State Examination (MMSE) Scores
Week 4
|
25.33 score on a scale
Standard Deviation 2.21
|
|
Mini Mental State Examination (MMSE) Scores
Week 8
|
26 score on a scale
Standard Deviation 3.13
|
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Mini Mental State Examination (MMSE) Scores
Week 16
|
25.55 score on a scale
Standard Deviation 2.51
|
SECONDARY outcome
Timeframe: Baseline to 16 weeks post-baselineThis 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.
Outcome measures
| Measure |
Simvastatin + L-Arginine + Tetrahydrobiopterin
n=10 Participants
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
|
|---|---|
|
Cognitive Assessment Screening Test (CAST)
|
31.4 score on a scale
Standard Deviation 5.46
|
SECONDARY outcome
Timeframe: Baseline to 16 weeks post-baselineThis 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.
Outcome measures
| Measure |
Simvastatin + L-Arginine + Tetrahydrobiopterin
n=10 Participants
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
|
|---|---|
|
Clinical Dementia Rating Scale (CDR)
CDR Score at Baseline
|
0.9 score on a scale
Standard Deviation .47
|
|
Clinical Dementia Rating Scale (CDR)
CDR Score at 16 weeks
|
0.9 score on a scale
Standard Deviation .47
|
SECONDARY outcome
Timeframe: Baseline to 16 weeks post-baselineMean 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.
Outcome measures
| Measure |
Simvastatin + L-Arginine + Tetrahydrobiopterin
n=10 Participants
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
|
|---|---|
|
Alzheimer's Disease Assessment Scale: Cognitive and Modified Version (ADAS-COG)
ADAS-COG Baseline
|
21.6 score on a scale
Standard Deviation 5.65
|
|
Alzheimer's Disease Assessment Scale: Cognitive and Modified Version (ADAS-COG)
ADAS-COG 16 weeks
|
21.9 score on a scale
Standard Deviation 8.9
|
SECONDARY outcome
Timeframe: Baseline to 4 weeks, 8 weeks and 16 weeks post-baselineThe 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.
Outcome measures
| Measure |
Simvastatin + L-Arginine + Tetrahydrobiopterin
n=10 Participants
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
|
|---|---|
|
Clinical Interview Based Impression of Change + Caregiver Input (CIBIC Plus)
Change in CIBIC score from baseline to 4 weeks
|
-.1 score on a scale
Standard Deviation 0.32
|
|
Clinical Interview Based Impression of Change + Caregiver Input (CIBIC Plus)
Change in CIBIC Score from 4 weeks to 8 weeks
|
.6 score on a scale
Standard Deviation .84
|
|
Clinical Interview Based Impression of Change + Caregiver Input (CIBIC Plus)
Change in CIBIC Score from 8 weeks to 16 weeks
|
-.1 score on a scale
Standard Deviation 1.29
|
Adverse Events
Simvastatin + L-Arginine + Tetrahydrobiopterin
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place