Clinical trial NCT01439555: Endothelial Facilitation in Alzheimer's Disease
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Alzheimer's Disease
Keywords: Early Alzheimer
Mild Cognitive Impairment
Drug treatment
Cerebral blood flow
Endothelial facilitation
Cognitive improvement
Lead sponsor: University of Massachusetts, Worcester
Sponsor class: OTHER
Collaborators: name: The Glass Foundation
First posted: 2011-09-23
Enrollment: 11
Sex: ALL
Minimum age (years): 55
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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


Eligibility criteria: 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.

Primary outcomes:
measure: Mean Change in Cerebral Blood Flow as Measured by Magnetic Resonance Imaging (MRI)
timeFrame: Baseline to 16 weeks
measure: Change in Cerebral Blood Flow as Measured by Arterial Spin Labeling During Magnetic Resonance Imaging (MRI)
timeFrame: Baseline to week 16
Secondary outcomes:
measure: Mini Mental State Examination (MMSE) Scores
timeFrame: Baseline to 4 weeks, 8 weeks and 16 weeks post-baseline
measure: Cognitive Assessment Screening Test (CAST)
timeFrame: Baseline to 16 weeks post-baseline
measure: Clinical Dementia Rating Scale (CDR)
timeFrame: Baseline to 16 weeks post-baseline
measure: Alzheimer's Disease Assessment Scale: Cognitive and Modified Version (ADAS-COG)
timeFrame: Baseline to 16 weeks post-baseline
measure: Clinical Interview Based Impression of Change + Caregiver Input (CIBIC Plus)
timeFrame: Baseline to 4 weeks, 8 weeks and 16 weeks post-baseline
Other outcomes:
Locations:
city: Worcester
country: United States
facility: UMass Medical School/ UMass Memorial Medical Center
state: Massachusetts
Study officials:
affiliation: UMass Medical School
name: Elizabeth R DeGrush, DO
role: PRINCIPAL_INVESTIGATOR
References: