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Endothelial Facilitation in Alzheimer's Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01439555
Recruitment Status : Active, not recruiting
First Posted : September 23, 2011
Last Update Posted : January 9, 2017
Sponsor:
Information provided by (Responsible Party):

Study Description
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

Condition or disease Intervention/treatment Phase
Alzheimer's Disease Drug: Simvastatin + L-Arginine + Tetrahydrobiopterin Phase 2

Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 10 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : November 2011
Estimated Primary Completion Date : December 2017
Estimated Study Completion Date : December 2017


Arms and Interventions

Arm Intervention/treatment
Experimental: 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
Drug: 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
Other Name: Tetrahydrobiopterin- Sapropterin - Kuvan


Outcome Measures

Primary Outcome Measures :
  1. Increase in regional cerebral blood flow over 4 months on studied medications [ Time Frame: 4 months from baseline ]
    Measurement of cerebral blood flow by Magnetic Resonance Imaging (MRI)- based Arterial Spin Labeling Cerebral Blood Flow, and Gadolinium Contrast-based cerebral blood flow


Secondary Outcome Measures :
  1. Psychometric evaluation [ Time Frame: 4 months ]
    Comparison of baseline psychometric performance with outcome at end of 4 month study


Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   55 Years to 85 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01439555


Locations
United States, Massachusetts
UMass Medical School/ UMass Memorial Medical Center
Worcester, Massachusetts, United States, 01655
Sponsors and Collaborators
University of Massachusetts, Worcester
Investigators
Principal Investigator: Elizabeth R DeGrush, DO UMass Medical School
More Information

Responsible Party: University of Massachusetts, Worcester
ClinicalTrials.gov Identifier: NCT01439555     History of Changes
Other Study ID Numbers: 13748
First Posted: September 23, 2011    Key Record Dates
Last Update Posted: January 9, 2017
Last Verified: January 2017

Keywords provided by University of Massachusetts, Worcester:
Early Alzheimer
Mild Cognitive Impairment
Drug treatment
Cerebral blood flow
Endothelial facilitation
Cognitive improvement

Additional relevant MeSH terms:
Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Simvastatin
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors