CompletedPhase 2Results posted

Endothelial Facilitation in Alzheimer's Disease

Endothelial Facilitation in Alzheimer's Disease. An Open Label Pilot Study of the Sequential and Cumulative Effects of Simvastatin, L-Arginine, and Sapropterin (Kuvan) on Cerebral Blood Flow and Cognitive Function in Patients With Alzheimer's Disease.

Lead sponsor

University of Massachusetts, Worcester

Assets

Simvastatin / Tetrahydrobiopterin

Listed sites

Recruiting sites

Enrollment

actual

Study population

Alzheimer’s disease

Key I/E criteria

•MMSE 15-26•Study partner/caregiver required

Primary endpoint

•Cerebral Blood Flow

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

Org study ID13748

NCT IDNCT01439555

Timeline

Milestones

Study first posted2011-09-23estimated

Study start2011-11 (month precision)

Primary completion2017-11actual (month precision)

Study completion2017-11actual (month precision)

Last update posted2019-07-30actual

Results first posted2019-07-30actual

Assets

Drug assets

Simvastatin Tetrahydrobiopterin

Study populations

Who this study enrolls

Alzheimer’s disease

Eligibility

Who can enroll

Minimum age55 Years

Maximum age85 Years

SexAll

Healthy volunteersNot accepted

Inclusion criteria

•Subjects must have mild Alzheimer's Disease or Mild Cognitive Impairment (MCI);

•age between 55-85;

•Mini Mental Status Exam (MMSE) between 15-26;

•a caregiver who can provide information, and bring patient to the sessions;

•no known allergies to any of the medications to be used;

•normal renal function; willingness of patient and spouse/responsible caregiver to participate

Exclusion criteria

•Significant Psychiatric disorder;

•stroke; current use of any of the test medications (e.g., statin, L-Arginine, Kuvan);

•phenylketonuria (PKU) ;

•elevated serum phenylalanine level (>10 mg/dL);

•allergy to any of the medications; current active malignancy;

•renal insufficiency (elevated creatinine above 1.3mg/dl);

•abnormal liver function (Alanine Aminotransferase (ALT) or Aspartate Transaminase (AST) 2x normal);

•other serious disease including coronary insufficiency or congestive heart failure, carotid stenosis greater than 50%, active peptic ulcer, urinary tract or other active infection, cancer (except skin cancer, or 5 years inactive breast or prostate cancer )etc.;

•pregnancy; or

•inability to come to UMass for follow-up. Subjects may continue to take anticholinesterase drugs for Alzheimer's Disease (Aricept, Exelon, Razadyne) and/or Namenda, if they have been on the drug(s) for at least 3 months. Subjects on levodopa and male subjects taking drugs for erectile dysfunction (Viagra, Cialis, Levitra) are cautioned regarding hypotension.

Endpoints (14)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Global cognition

Neuroimaging

Function / daily living

Global cognition

8 endpoints

Secondary/protocol endpoint

Mini Mental State Examination (MMSE) Scores

Time frame:Baseline to 4 weeks, 8 weeks and 16 weeks post-baseline

Mini-Mental State Examination (MMSE)

change from baseline, improvement

Secondary/protocol endpoint

Cognitive Assessment Screening Test (CAST)

Time frame:Baseline to 16 weeks post-baseline

change from baseline, improvement

Secondary/protocol endpoint

Clinical Dementia Rating Scale (CDR)

Time frame:Baseline to 16 weeks post-baseline

categorical status, descriptive

Secondary/protocol endpoint

Alzheimer's Disease Assessment Scale: Cognitive and Modified Version (ADAS-COG)

Time frame:Baseline to 16 weeks post-baseline

ADAS-Cog

descriptive

Secondary/registry result

Mini Mental State Examination (MMSE) Scores

Time frame:Baseline to 4 weeks, 8 weeks and 16 weeks post-baseline

Mini-Mental State Examination (MMSE)

change from baseline, improvement

Posted result

Group	Value (mean), score on a scale	Standard deviation
Simvastatin + L-Arginine + TetrahydrobiopterinBaselinen=10 Participants	24.2	3.155
Week 4n=10 Participants	25.33	2.21
Week 8n=10 Participants	26	3.13
Week 16n=10 Participants	25.55	2.51

Secondary/registry result

Cognitive Assessment Screening Test (CAST)

Time frame:Baseline to 16 weeks post-baseline

change from baseline, improvement

Posted result

Group	Value (mean), score on a scale	Standard deviation
Simvastatin + L-Arginine + Tetrahydrobiopterinn=10 Participants	31.4	5.46

Secondary/registry result

Clinical Dementia Rating Scale (CDR)

Time frame:Baseline to 16 weeks post-baseline

categorical status, descriptive

Posted result

Group	Value (mean), score on a scale	Standard deviation
Simvastatin + L-Arginine + TetrahydrobiopterinCDR Score at Baselinen=10 Participants	0.9	.47
CDR Score at 16 weeksn=10 Participants	0.9	.47

Secondary/registry result

Alzheimer's Disease Assessment Scale: Cognitive and Modified Version (ADAS-COG)

Time frame:Baseline to 16 weeks post-baseline

ADAS-Cog

descriptive

Posted result

Group	Value (mean), score on a scale	Standard deviation
Simvastatin + L-Arginine + TetrahydrobiopterinADAS-COG Baselinen=10 Participants	21.6	5.65
ADAS-COG 16 weeksn=10 Participants	21.9	8.9

Function / daily living

2 endpoints

Secondary/protocol endpoint

Clinical Interview Based Impression of Change + Caregiver Input (CIBIC Plus)

Time frame:Baseline to 4 weeks, 8 weeks and 16 weeks post-baseline

descriptive

Secondary/registry result

Clinical Interview Based Impression of Change + Caregiver Input (CIBIC Plus)

Time frame:Baseline to 4 weeks, 8 weeks and 16 weeks post-baseline

descriptive

Posted result

Group	Value (mean), score on a scale	Standard deviation
Simvastatin + L-Arginine + TetrahydrobiopterinChange in CIBIC score from baseline to 4 weeksn=10 Participants	-.1	0.32
Change in CIBIC Score from 4 weeks to 8 weeksn=10 Participants	.6	.84
Change in CIBIC Score from 8 weeks to 16 weeksn=10 Participants	-.1	1.29

Neuroimaging

4 endpoints

Primary/protocol endpoint

Mean Change in Cerebral Blood Flow as Measured by Magnetic Resonance Imaging (MRI)

Time frame:Baseline to 16 weeks

change from baseline, improvement

Primary/protocol endpoint

Change in Cerebral Blood Flow as Measured by Arterial Spin Labeling During Magnetic Resonance Imaging (MRI)

Time frame:Baseline to week 16

change from baseline, improvement

Primary/registry result

Mean Change in Cerebral Blood Flow as Measured by Magnetic Resonance Imaging (MRI)

Time frame:Baseline to 16 weeks

change from baseline, improvement

Posted result

Group	Value (mean), ml/110g/min	Standard deviation
Simvastatin + L-Arginine + TetrahydrobiopterinBaselinen=6 Participants	0.621528	0.116513988
Week 4n=6 Participants	0.6447692	0.070388324
Week 8n=6 Participants	0.654822667	0.024032403
Week 16n=6 Participants	0.579838667	0.091658076

Primary/registry result

Change in Cerebral Blood Flow as Measured by Arterial Spin Labeling During Magnetic Resonance Imaging (MRI)

Time frame:Baseline to week 16

change from baseline, improvement

Publications (1)

Bibliography

Records linked to this trial through ClinicalTrials.gov references, PubMed NCT search, and curated study seeds. 'Canonical' marks design/result papers; others are registry references or candidates.

Registry references + supporting bibliography

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.
PMID36115980via DERIVED

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 21, 2026

Endpoint classificationDelfa ADRD endpoint taxonomy

Results tableClinicalTrials.gov results section

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 21, 2026 snapshot.