Huperzine A in Alzheimer's Disease

NCT ID: NCT00083590

Last Updated: 2008-02-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

150 participants

Study Classification

INTERVENTIONAL

Study Start Date

2004-04-30

Study Completion Date

2007-11-30

Brief Summary

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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.

Detailed Description

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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).

Conditions

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Alzheimer Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Interventions

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Huperzine A

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

55 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Alzheimer's Disease Cooperative Study (ADCS)

OTHER

Sponsor Role collaborator

Neuro-Hitech

INDUSTRY

Sponsor Role collaborator

National Institute on Aging (NIA)

NIH

Sponsor Role lead

Principal Investigators

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Paul S. Aisen, MD

Role: PRINCIPAL_INVESTIGATOR

Georgetown University Medical Center, Memory Disorders Program

Locations

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University of Alabama

Birmingham, Alabama, United States

Site Status

Banner Alzheimer's Institute

Phoenix, Arizona, United States

Site Status

University of California, Irvine

Irvine, California, United States

Site Status

University of California, San Diego, Alzheimer's Disease Research Center

La Jolla, California, United States

Site Status

University of Southern California

Los Angeles, California, United States

Site Status

University of California, Davis

Sacramento, California, United States

Site Status

Georgetown University Medical Center, Memory Disorders Program

Washington D.C., District of Columbia, United States

Site Status

Howard University School of Medicine

Washington D.C., District of Columbia, United States

Site Status

MD Clinical

Fort Lauderdale, Florida, United States

Site Status

Roskamp Institute Memory Clinic

Tampa, Florida, United States

Site Status

University of South Florida, Suncoast Alzheimer's and Gerontology Center

Tampa, Florida, United States

Site Status

Premiere Research Institute

West Palm Beach, Florida, United States

Site Status

Emory University

Atlanta, Georgia, United States

Site Status

Rush Alzheimer's Disease Center, Rush University Medical Center

Chicago, Illinois, United States

Site Status

ICPS Group

Boston, Massachusetts, United States

Site Status

University of Nevada School of Medicine

Las Vegas, Nevada, United States

Site Status

Alzheimer's Research Corporation

Paterson, New Jersey, United States

Site Status

University of Medicine and Dentistry of New Jersey

Piscataway, New Jersey, United States

Site Status

Albany Medical Center

Albany, New York, United States

Site Status

New York University Medical Center

New York, New York, United States

Site Status

Mount Sinai School of Medicine

New York, New York, United States

Site Status

Nathan S. Kline Institute for Psychiatric Research

Orangeburg, New York, United States

Site Status

University of Rochester Medical Center

Rochester, New York, United States

Site Status

University of North Carolina

Chapel Hill, North Carolina, United States

Site Status

Oregon Health and Science University

Portland, Oregon, United States

Site Status

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Site Status

Medical University of South Carolina

North Charleston, South Carolina, United States

Site Status

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Site Status

University of Vermont College of Medicine

Burlington, Vermont, United States

Site Status

Countries

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United States

References

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Bai DL, Tang XC, He XC. Huperzine A, a potential therapeutic agent for treatment of Alzheimer's disease. Curr Med Chem. 2000 Mar;7(3):355-74. doi: 10.2174/0929867003375281.

Reference Type BACKGROUND
PMID: 10637369 (View on PubMed)

Ved HS, Koenig ML, Dave JR, Doctor BP. Huperzine A, a potential therapeutic agent for dementia, reduces neuronal cell death caused by glutamate. Neuroreport. 1997 Mar 3;8(4):963-8. doi: 10.1097/00001756-199703030-00029.

Reference Type BACKGROUND
PMID: 9141073 (View on PubMed)

Mazurek A: An open-label trial of huperzine A in the treatment of Alzheimer's disease. Alternative Therapies 5(2): 97-98, March 16, 2000.

Reference Type BACKGROUND

Other Identifiers

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ADC-023

Identifier Type: -

Identifier Source: secondary_id

IND 63,997

Identifier Type: -

Identifier Source: secondary_id

IA0052

Identifier Type: -

Identifier Source: org_study_id

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