ALADDIN Study - Phase III: Antigonadotropin-Leuprolide in Alzheimer's Disease Drug INvestigation (VP-AD-301)

Alzheimer's Disease Clinical Trial

Official title:

A Double-Blind Placebo-Controlled Study of VP4896 For the Treatment of Mild-to-Moderate Alzheimer's Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00231946
• Other study ID #: IA0084
• Status: Completed
• Phase: Phase 3
• First received: September 30, 2005
• Last updated: September 18, 2007
• Start date: September 2005

Study information

• Verified date: September 2007
• Source: National Institute on Aging (NIA)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The study is designed to investigate the activity of the hormone drug leuprolide acetate in stabilizing cognitive function in mild-to-moderate AD patients.

Description:

VP4896 is a gonadotropin releasing hormone (GnRH) agonist that binds to and inactivates GnRH receptors on the pituitary gland. This decreases the amount of luteinizing hormone released by the pituitary. The hypothesis upon which this trial is designed is that luteinizing hormone is the cause of Alzheimer's disease. VP4896 decreases the amount of luteinizing hormone in the body and, therefore, may decrease or halt the progression of Alzheimer's disease.

This is a double-blind, placebo-controlled, study designed to assess the safety and efficacy of VP4896 (a novel formulation of leuprolide acetate) in the treatment of subjects with mild-to-moderate AD. The study duration is 56 weeks. Approximately 555 participants will be recruited from approximately 80 sites in the United States, Canada, and South America.

The study drug will be administered every eight weeks over a 48 week period. Male subjects randomized to active treatment will also receive testosterone replacement gel.

The change from baseline in ADAS-Cog (cognitive test) score at Week 50 and ADCS-CGIC (global cognitive and behavioral measure) at Week 50 will be the primary efficacy endpoints. Safety will be assessed at all visits and by phone at Week 1.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 555
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 60 Years and older

Eligibility

Inclusion Criteria:

• 60 years of age or older

• Diagnosis of probable mild-to-moderate Alzheimer's Disease

• On a stable dose of an acetylcholinesterase inhibitor (including, but not limited to:

donepezil, galantamine, rivastigmine, and tacrine) for at least 120 days prior to baseline and will likely remain on the drug throughout the trial; all participants must be on acetylcholinesterase inhibitors

• No other significant or interfering medical conditions

Exclusion Criteria:

• Significant neurological disease affecting the brain or psychiatric disease other than AD, such as current untreated major depression, schizophrenia, epilepsy, Parkinson's disease, Creutzfeldt-Jakob's disease, or clinical episode of stroke

• Laboratory or clinical signs of untreated, clinically significant abnormal thyroid function, in the Investigator's opinion

• Received other investigational drugs within 30 days or 5 half-lives prior to baseline, whichever is longer

• Taking other medications, with the exception of estrogen, known to affect serum gonadotropin (Gn) concentrations, including but not limited to goserelin, danazol, or leuprolide

• Other exclusion criteria exist--eligibility can be assessed by the trial site

Study Design

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

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Disease

Intervention

Drug:
• VP4896

Locations

Country	Name	City	State
Canada	Queen Elizabeth II Health Sciences Centre	Halifax	Nova Scotia
Canada	The Medical Arts Health Research Group	Penticton	British Columbia
Canada	Novabyss Inc.	Sherbrooke	Quebec
Canada	Toronto Memory Program (Neurology Research Inc.)	Toronto	Ontario
United States	Upstate Clinical Research, LLC	Albany	New York
United States	Albuquerque Neuroscience Inc.	Albuquerque	New Mexico
United States	Innovative Clinical Research Center	Alexandria	Virginia
United States	Southwestern Vermont Medical Center	Bennington	Vermont
United States	ICPS Group	Boston	Massachusetts
United States	Meridien Research	Brookville	Florida
United States	Ohio State University Medical Center	Columbus	Ohio
United States	Comprehensive Neuroscience, Inc.	Darien	Connecticut
United States	Brain Matters Research	Delray Beach	Florida
United States	Colorado Neurology & Headache Center	Denver	Colorado
United States	Radiant Research	Denver	Colorado
United States	Memory Research Institute	East Providence	Rhode Island
United States	Pharmaceutical Research-Oregon, Inc.	Eugene	Oregon
United States	Hunterdon Medical Center	Flemington	New Jersey
United States	Margolin Brain Institute	Fresno	California
United States	Radiant Research - Greer	Greer	South Carolina
United States	Geriatric and Adult Psychiatry	Hamden	Connecticut
United States	Berma Research Group	Hialeah	Florida
United States	Kuakani Medical Center	Honolulu	Hawaii
United States	University of Texas Health Science Center at Houston	Houston	Texas
United States	Clinical Trial Center, LLC.	Jenkintown	Pennsylvania
United States	Bay Area Research Institute	Lafayette	California
United States	Anderson Clinical Research	Loma Linda	California
United States	Pharmacology Research Institute	Los Alamitos	California
United States	David Trader	Los Angeles	California
United States	Medark Clinical Trials	Morgantown	North Carolina
United States	Synergy Clinical Research	National City	California
United States	Pharmacology Research Institute	Newport Beach	California
United States	Pearl Clinical Research, Inc.	Norristown	Pennsylvania
United States	Pharmacology Research Institute	Northridge	California
United States	North County Neurology Assoc.	Oceanside	California
United States	IPS Research Company	Oklahoma City	Oklahoma
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Pivotal Research Centers	Peoria	Arizona
United States	Neurology Clinical Research, LLC	Plantation	Florida
United States	Butler Hospital	Providence	Rhode Island
United States	Norman Gordon, MD	Providence	Rhode Island
United States	Raleigh Neurology Associates, P.A.	Raleigh	North Carolina
United States	Pharmacology Research Institute	Riverside	California
United States	Pivotal Research Centers	Royal Oak	Michigan
United States	Bexar Diagnostic Medicine Associates	San Antonio	Texas
United States	Pacific Research Network	San Diego	California
United States	San Francisco Clinical Research Center	San Francisco	California
United States	Neurological Research Institute	Santa Monica	California
United States	Roskamp Institute	Sarasota	Florida
United States	Booker, J. Gary, MD, APMC	Shreveport	Louisiana
United States	Meridien Research	St. Petersburg	Florida
United States	Meridien Research	Tampa	Florida
United States	Neurology Center of Ohio	Toledo	Ohio
United States	Torrance Clinical Research	Torrance	California
United States	NeuroSpecialists, PLLC	Tucson	Arizona
United States	Palm Beach Neurological Group	West Palm Beach	Florida
United States	Quantum Laboratories	West Palm Beach	Florida
United States	Grayline Clinical Drug Trials	Wichita Falls	Texas
United States	Piedmont Medical Research Associates	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Voyager Pharmaceutical Corporation

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (5)

Bowen RL, Atwood CS. Living and dying for sex. A theory of aging based on the modulation of cell cycle signaling by reproductive hormones. Gerontology. 2004 Sep-Oct;50(5):265-90. Review. — View Citation

Bowen RL, Verdile G, Liu T, Parlow AF, Perry G, Smith MA, Martins RN, Atwood CS. Luteinizing hormone, a reproductive regulator that modulates the processing of amyloid-beta precursor protein and amyloid-beta deposition. J Biol Chem. 2004 May 7;279(19):20539-45. Epub 2004 Feb 9. — View Citation

Gregory CW, Bowen RL. Novel therapeutic strategies for Alzheimer's disease based on the forgotten reproductive hormones. Cell Mol Life Sci. 2005 Feb;62(3):313-9. Review. — View Citation

Webber KM, Bowen R, Casadesus G, Perry G, Atwood CS, Smith MA. Gonadotropins and Alzheimer's disease: the link between estrogen replacement therapy and neuroprotection. Acta Neurobiol Exp (Wars). 2004;64(1):113-8. Review. — View Citation

Zhu X, McShea A, Harris PL, Raina AK, Castellani RJ, Funk JO, Shah S, Atwood C, Bowen R, Bowser R, Morelli L, Perry G, Smith MA. Elevated expression of a regulator of the G2/M phase of the cell cycle, neuronal CIP-1-associated regulator of cyclin B, in Alzheimer's disease. J Neurosci Res. 2004 Mar 1;75(5):698-703. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cognitive assessment and Caregiver's impression of change at baseline and at weeks 8, 24, 34, and 50.
Secondary	Ability to perform Activities of Daily Living (ADL) at baseline and weeks 8, 24, 34, and 50. Impression of disease severity assessment at week 50.

External Links

•   Alzheimer's Association