Huperzine A in Alzheimer's Disease

February 19, 2008 updated by: National Institute on Aging (NIA)

A Multi-Center, Double-Blind, Placebo-Controlled Therapeutic Trial to Determine Whether Natural Huperzine A Improves Cognitive Function

The present study will evaluate the safety and efficacy of the Chinese herb huperzine A in the treatment of Alzheimer's disease (AD) in a randomized controlled trial of its effect on cognitive function.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Huperzine A is a natural cholinesterase inhibitor derived from the Chinese herb Huperzia serrata. There is evidence that huperzine A may compare favorably in symptomatic efficacy to cholinesterase inhibitors currently in use. In addition, huperzine A has antioxidant and neuroprotective properties that suggest that it may be useful as a disease-modifying treatment for Alzheimer's disease (AD). The drug is currently available as a nutraceutical in this country, and is being used by some U.S. clinicians to treat AD. However, there have been no controlled clinical trials outside China assessing its toxicity and efficacy. The present study will evaluate huperzine A in the treatment of AD in a randomized controlled trial of its effect on cognitive function.

The primary aim of this multicenter, double-blind, placebo-controlled therapeutic Phase II trial is to determine whether treatment with huperzine A 200µg twice a day improves cognitive function in individuals with AD. Secondary aims of this study are to: a) determine whether treatment with huperzine A 400µg twice a day improves cognitive function in individuals with AD; b) determine the effect of huperzine A treatment on global clinical status, activities of daily living, and behavior in AD; c) evaluate the tolerability of huperzine A treatment at dosages of 200µg twice a day and 400µg twice a day in AD; and d) determine the relationship between blood cholinesterase activity and cognitive function in individuals with AD treated with huperzine A. A total of 150 participants will be randomly assigned to three groups of equal size. This will allow a comparison of huperzine A 200µg twice a day, huperzine A 400µg twice a day, and placebo. The primary outcome measures will be the change in score on the ADAScog at the 16 week visit. Secondary outcome measures include the ADCS clinical global impression of change (CGIC) (Schneider et al 1997) and activities of daily living (ADL) (Galasko et al 1997) scales, and the Neuropsychiatric Inventory (Cummings 1997). Volunteers must be able to participate in the study for 24 weeks and make 9 visits to the trial site.

At the end of the double-blind study, participants will be invited to continue huperzine A treatment for 6 months in an open-label extension phase. Participants will receive 200µg of huperzine A twice a day for six consecutive months, and will be assessed at 3-month intervals (months 6, 9, and 12, with month 6 assessments coinciding with the final visit of the double-blind phase).

Study Type

Interventional

Enrollment (Anticipated)

150

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294
        • University of Alabama
    • Arizona
      • Phoenix, Arizona, United States, 85006
        • Banner Alzheimer's Institute
    • California
      • Irvine, California, United States, 92697
        • University of California, Irvine
      • La Jolla, California, United States, 92037
        • University of California, San Diego, Alzheimer's Disease Research Center
      • Los Angeles, California, United States, 90033
        • University of Southern California
      • Sacramento, California, United States, 95817
        • University of California, Davis
    • District of Columbia
      • Washington, District of Columbia, United States, 20057
        • Georgetown University Medical Center, Memory Disorders Program
      • Washington, DC, District of Columbia, United States, 20060
        • Howard University School of Medicine
    • Florida
      • Fort Lauderdale, Florida, United States, 33321
        • MD Clinical
      • Tampa, Florida, United States, 33617
        • Roskamp Institute Memory Clinic
      • Tampa, Florida, United States, 33617
        • University of South Florida, Suncoast Alzheimer's and Gerontology Center
      • West Palm Beach, Florida, United States, 33407
        • Premiere Research Institute
    • Georgia
      • Atlanta, Georgia, United States, 30329
        • Emory University
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Rush Alzheimer's Disease Center, Rush University Medical Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02131
        • ICPS Group
    • Nevada
      • Las Vegas, Nevada, United States, 89102
        • University of Nevada School of Medicine
    • New Jersey
      • Manchester, New Jersey, United States, 08759
        • Alzheimer's Research Corporation
      • Piscataway, New Jersey, United States, 08855
        • University of Medicine and Dentistry of New Jersey
    • New York
      • Albany, New York, United States, 12208
        • Albany Medical Center
      • New York, New York, United States, 10016
        • New York University Medical Center
      • New York, New York, United States, 10029
        • Mount Sinai School of Medicine
      • Orangeburg, New York, United States, 10962
        • Nathan S. Kline Institute for Psychiatric Research
      • Rochester, New York, United States, 14620
        • University of Rochester Medical Center
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
        • University of North Carolina
    • Oregon
      • Portland, Oregon, United States, 97201
        • Oregon Health and Science University
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213
        • University of Pittsburgh
    • South Carolina
      • North Charleston, South Carolina, United States, 29406
        • Medical University of South Carolina
    • Texas
      • Dallas, Texas, United States, 75390
        • University of Texas Southwestern Medical Center
    • Vermont
      • Burlington, Vermont, United States, 05401
        • University of Vermont College of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

55 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

The selection process is designed to allow enrollment of all people with AD who are likely to be testable at the conclusion of the study period, and who do not have concurrent medical conditions or medications that might influence cognitive testing or that would increase the risk of treatment. Women and members of minority groups are encouraged to volunteer.

Inclusion Criteria:

  • NINDS/ADRDA criteria for probable AD.
  • Mini Mental State Examination between 10 and 24, inclusive.
  • Stable medical condition for 3 months prior to screening.
  • Supervision available for administration of study medications.
  • Study partner to accompany participant to all scheduled visits.
  • Fluent in English or Spanish.
  • Age 55 years or older.
  • Modified Hachinski score equal to or less than 4.
  • CT or MRI since onset of memory impairment demonstrating absence of clinically significant focal lesion.
  • Able to complete baseline assessments.
  • 6 years of education, or work history sufficient to exclude mental retardation.
  • Able to ingest oral medication.
  • Stable doses of medications for 4 weeks prior to screening.
  • Physically acceptable for this study as confirmed by medical history, physical exam, neurological exam and clinical tests.

Exclusion Criteria:

  • History of active peptic ulcer disease within 1 year of screening.
  • Clinically significant cardiac arrhythmia.
  • Resting pulse less than 50.
  • Active neoplastic (cancer) disease (skin tumors other than melanoma are not excluded; participants with stable prostate cancer may be included at the discretion of the Project Director).
  • Use of another investigational agent within 2 months of screening.
  • History of clinically significant stroke.
  • Current evidence or history in the past 2 years of epilepsy, focal brain lesion, head injury with loss of consciousness and/or immediate confusion after the injury, or DSM-IV criteria for any major psychiatric disorder including psychosis, major depression, bipolar disorder, alcohol or substance abuse.
  • Blindness, deafness, language difficulties or any other disability which may prevent the participant from participating or cooperating in the protocol.
  • Residence in a skilled nursing facility; but patients in an assisted living facility are acceptable.

Excluded Medications:

  • Use of cholinesterase inhibitors (galantamine, rivastigmine, donepezil, and tacrine) within 2 months of screening.
  • Regular use of narcotic analgesics (>2 doses per week) within 4 weeks of screening.
  • Use of medications with significant central nervous system anticholinergic activity within 2 months of screening (e.g. tricyclic antidepressants, diphenhydramine).
  • Use of anti-Parkinsonian medications (including Sinemet, amantadine, bromocriptine, pergolide, selegiline) within 2 months of screening.
  • Participation in any other investigational drug study within 2 months of screening (individuals may not participate in any other drug study while participating in this protocol).
  • Use of estrogen is allowed if the dose has been stable for 3 months prior to screening.
  • Use of vitamin E is allowed if the dose has been stable for 3 months prior to screening.
  • Use of memantine is allowed if the dose has been stable for 3 months prior to screening.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Paul S. Aisen, MD, Georgetown University Medical Center, Memory Disorders Program

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2004

Primary Completion (Actual)

November 1, 2007

Study Completion (Actual)

November 1, 2007

Study Registration Dates

First Submitted

May 26, 2004

First Submitted That Met QC Criteria

May 26, 2004

First Posted (Estimate)

May 27, 2004

Study Record Updates

Last Update Posted (Estimate)

February 21, 2008

Last Update Submitted That Met QC Criteria

February 19, 2008

Last Verified

February 1, 2008

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact [email protected]. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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