Huperzine A in Alzheimer's Disease

Alzheimer Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00083590
• Other study ID #: IA0052
• Secondary ID: ADC-023IND 63,99
• Status: Completed
• Phase: Phase 2
• First received: May 26, 2004
• Last updated: February 19, 2008
• Start date: April 2004
• Est. completion date: November 2007

Study information

• Verified date: February 2008
• Source: National Institute on Aging (NIA)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 150
• Est. completion date: November 2007
• Est. primary completion date: November 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 55 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Alzheimer Disease

Intervention

Drug:
• Huperzine A

Locations

Country	Name	City	State
United States	Albany Medical Center	Albany	New York
United States	Emory University	Atlanta	Georgia
United States	University of Alabama	Birmingham	Alabama
United States	ICPS Group	Boston	Massachusetts
United States	University of Vermont College of Medicine	Burlington	Vermont
United States	University of North Carolina	Chapel Hill	North Carolina
United States	Rush Alzheimer's Disease Center, Rush University Medical Center	Chicago	Illinois
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	MD Clinical	Fort Lauderdale	Florida
United States	University of California, Irvine	Irvine	California
United States	University of California, San Diego, Alzheimer's Disease Research Center	La Jolla	California
United States	University of Nevada School of Medicine	Las Vegas	Nevada
United States	University of Southern California	Los Angeles	California
United States	Alzheimer's Research Corporation	Manchester	New Jersey
United States	Mount Sinai School of Medicine	New York	New York
United States	New York University Medical Center	New York	New York
United States	Medical University of South Carolina	North Charleston	South Carolina
United States	Nathan S. Kline Institute for Psychiatric Research	Orangeburg	New York
United States	Banner Alzheimer's Institute	Phoenix	Arizona
United States	University of Medicine and Dentistry of New Jersey	Piscataway	New Jersey
United States	University of Pittsburgh	Pittsburgh	Pennsylvania
United States	Oregon Health and Science University	Portland	Oregon
United States	University of Rochester Medical Center	Rochester	New York
United States	University of California, Davis	Sacramento	California
United States	Roskamp Institute Memory Clinic	Tampa	Florida
United States	University of South Florida, Suncoast Alzheimer's and Gerontology Center	Tampa	Florida
United States	Georgetown University Medical Center, Memory Disorders Program	Washington	District of Columbia
United States	Howard University School of Medicine	Washington, DC	District of Columbia
United States	Premiere Research Institute	West Palm Beach	Florida

Sponsors (3)

Lead Sponsor	Collaborator
National Institute on Aging (NIA)	Alzheimer's Disease Cooperative Study (ADCS), Neuro-Hitech

Country where clinical trial is conducted

United States, 

References & Publications (3)

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. Review. — View Citation

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.

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. — View Citation