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Completed

NCT Number: NCT01439555

Endothelial Facilitation in Alzheimer's Disease

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

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Key information

Conditions

Alzheimer's Disease Alzheimer Disease Brain Diseases Central Nervous System Diseases Cognition Disorders Cognitive Dysfunction Dementia Mental Disorders Nervous System Diseases Neurocognitive Disorders Neurodegenerative Diseases Tauopathies

Age range

55 year–85 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

UMass Medical School/ UMass Memorial Medical Center

Worcester, Massachusetts, 01655, United States

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

simvastatin

Drug

Simvastatin, 40 mg per day orally

Other names: Tetrahydrobiopterin

L-arginine

Drug

L-Arginine, 2 Gm four times per day orally;

Tetrahydrobiopterin

Drug

Tetrahydrobiopterin 20 mg/kg/day orally

Other names: Kuvan, Sapropterin

Primary outcomes

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

    Time frame: 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)

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

    Time frame: Baseline to week 16

    Data not available as files corrupted and could not be analyzed

Secondary outcomes

  1. Mini Mental State Examination (MMSE) Scores

    Time frame: 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.

  2. Cognitive Assessment Screening Test (CAST)

    Time frame: 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.

  3. Clinical Dementia Rating Scale (CDR)

    Time frame: 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.

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

    Time frame: 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.

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

    Time frame: 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.

Sponsors and collaborators

Lead sponsor

University of Massachusetts, Worcester

Other

Collaborators

  • The Glass Foundation

Registry information

Official study 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.

Important dates

Study start
2011
Primary completion
2017
Study completion
2017
First posted
Sep 23, 2011
Registry last updated
Jul 30, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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