Endothelial Facilitation in Alzheimer's Disease

Phase 2

Completed

Conditions: Alzheimer's Disease

Interventions: Drug: Simvastatin
Drug: L-Arginine
Drug: Tetrahydrobiopterin

Registration Number: NCT01439555

Lead Sponsor: University of Massachusetts, Worcester

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

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 11

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Simvastatin + L-Arginine + Tetrahydrobiopterin	Simvastatin	Simvastatin, 40 mg per day orally; L-Arginine, 2 Gm four times per day orally; Tetrahydrobiopterin 20 mg/kg/day orally
Simvastatin + L-Arginine + Tetrahydrobiopterin	Tetrahydrobiopterin	Simvastatin, 40 mg per day orally; L-Arginine, 2 Gm four times per day orally; Tetrahydrobiopterin 20 mg/kg/day orally
Simvastatin + L-Arginine + Tetrahydrobiopterin	L-Arginine	Simvastatin, 40 mg per day orally; L-Arginine, 2 Gm four times per day orally; Tetrahydrobiopterin 20 mg/kg/day orally

Primary Outcome Measures

Name	Time	Method
Mean Change in Cerebral Blood Flow as Measured by Magnetic Resonance Imaging (MRI)	Baseline to 16 weeks	Measurement of changes to cerebral blood flow (ml/110g/min) in regions of interest as measured using Magnetic Resonance Imaging (MRI)
Change in Cerebral Blood Flow as Measured by Arterial Spin Labeling During Magnetic Resonance Imaging (MRI)	Baseline to week 16	Data not available as files corrupted and could not be analyzed

Secondary Outcome Measures

Name	Time	Method
Mini Mental State Examination (MMSE) Scores	Baseline to 4 weeks, 8 weeks and 16 weeks post-baseline	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.
Cognitive Assessment Screening Test (CAST)	Baseline to 16 weeks post-baseline	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.
Alzheimer's Disease Assessment Scale: Cognitive and Modified Version (ADAS-COG)	Baseline to 16 weeks post-baseline	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.
Clinical Interview Based Impression of Change + Caregiver Input (CIBIC Plus)	Baseline to 4 weeks, 8 weeks and 16 weeks post-baseline	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.
Clinical Dementia Rating Scale (CDR)	Baseline to 16 weeks post-baseline	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.