Clinical trial NCT00231946: ALADDIN Study - Phase III: Antigonadotropin-Leuprolide in Alzheimer's Disease Drug INvestigation (VP-AD-301)
Official title: A Double-Blind Placebo-Controlled Study of VP4896 For the Treatment of Mild-to-Moderate Alzheimer's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Alzheimer's Disease
Keywords: gonadotropins
hormone therapy
HRT
Antigonadotropin
Leuprolide
Lead sponsor: National Institute on Aging (NIA)
Sponsor class: NIH
First posted: 2005-10-04
Enrollment: 555
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Cognitive assessment and Caregiver's impression of change at baseline and at weeks 8, 24, 34, and 50.
Secondary outcomes:
measure: 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.
Other outcomes:
Locations:
city: Peoria
country: United States
facility: Pivotal Research Centers
state: Arizona
city: Tucson
country: United States
facility: NeuroSpecialists, PLLC
state: Arizona
city: Fresno
country: United States
facility: Margolin Brain Institute
state: California
city: Lafayette
country: United States
facility: Bay Area Research Institute
state: California
city: Loma Linda
country: United States
facility: Anderson Clinical Research
state: California
city: Los Alamitos
country: United States
facility: Pharmacology Research Institute
state: California
city: Los Angeles
country: United States
facility: David Trader
state: California
city: National City
country: United States
facility: Synergy Clinical Research
state: California
city: Newport Beach
country: United States
facility: Pharmacology Research Institute
state: California
city: Northridge
country: United States
facility: Pharmacology Research Institute
state: California
city: Oceanside
country: United States
facility: North County Neurology Assoc.
state: California
city: Riverside
country: United States
facility: Pharmacology Research Institute
state: California
city: San Diego
country: United States
facility: Pacific Research Network
state: California
city: San Francisco
country: United States
facility: San Francisco Clinical Research Center
state: California
city: Santa Monica
country: United States
facility: Neurological Research Institute
state: California
city: Torrance
country: United States
facility: Torrance Clinical Research
state: California
city: Denver
country: United States
facility: Radiant Research
state: Colorado
city: Denver
country: United States
facility: Colorado Neurology & Headache Center
state: Colorado
city: Darien
country: United States
facility: Comprehensive Neuroscience, Inc.
state: Connecticut
city: Hamden
country: United States
facility: Geriatric and Adult Psychiatry
state: Connecticut
city: Brookville
country: United States
facility: Meridien Research
state: Florida
city: Delray Beach
country: United States
facility: Brain Matters Research
state: Florida
city: Hialeah
country: United States
facility: Berma Research Group
state: Florida
city: Plantation
country: United States
facility: Neurology Clinical Research, LLC
state: Florida
city: Sarasota
country: United States
facility: Roskamp Institute
state: Florida
city: St. Petersburg
country: United States
facility: Meridien Research
state: Florida
city: Tampa
country: United States
facility: Meridien Research
state: Florida
city: West Palm Beach
country: United States
facility: Palm Beach Neurological Group
state: Florida
city: West Palm Beach
country: United States
facility: Quantum Laboratories
state: Florida
city: Honolulu
country: United States
facility: Kuakani Medical Center
state: Hawaii
city: Shreveport
country: United States
facility: Booker, J. Gary, MD, APMC
state: Louisiana
city: Boston
country: United States
facility: ICPS Group
state: Massachusetts
city: Royal Oak
country: United States
facility: Pivotal Research Centers
state: Michigan
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Flemington
country: United States
facility: Hunterdon Medical Center
state: New Jersey
city: Albuquerque
country: United States
facility: Albuquerque Neuroscience Inc.
state: New Mexico
city: Albany
country: United States
facility: Upstate Clinical Research, LLC
state: New York
city: Morgantown
country: United States
facility: Medark Clinical Trials
state: North Carolina
city: Raleigh
country: United States
facility: Raleigh Neurology Associates, P.A.
state: North Carolina
city: Winston-Salem
country: United States
facility: Piedmont Medical Research Associates
state: North Carolina
city: Columbus
country: United States
facility: Ohio State University Medical Center
state: Ohio
city: Toledo
country: United States
facility: Neurology Center of Ohio
state: Ohio
city: Oklahoma City
country: United States
facility: IPS Research Company
state: Oklahoma
city: Eugene
country: United States
facility: Pharmaceutical Research-Oregon, Inc.
state: Oregon
city: Jenkintown
country: United States
facility: Clinical Trial Center, LLC.
state: Pennsylvania
city: Norristown
country: United States
facility: Pearl Clinical Research, Inc.
state: Pennsylvania
city: East Providence
country: United States
facility: Memory Research Institute
state: Rhode Island
city: Providence
country: United States
facility: Butler Hospital
state: Rhode Island
city: Providence
country: United States
facility: Norman Gordon, MD
state: Rhode Island
city: Greer
country: United States
facility: Radiant Research - Greer
state: South Carolina
city: Houston
country: United States
facility: University of Texas Health Science Center at Houston
state: Texas
city: San Antonio
country: United States
facility: Bexar Diagnostic Medicine Associates
state: Texas
city: Wichita Falls
country: United States
facility: Grayline Clinical Drug Trials
state: Texas
city: Bennington
country: United States
facility: Southwestern Vermont Medical Center
state: Vermont
city: Alexandria
country: United States
facility: Innovative Clinical Research Center
state: Virginia
city: Penticton
country: Canada
facility: The Medical Arts Health Research Group
state: British Columbia
city: Halifax
country: Canada
facility: Queen Elizabeth II Health Sciences Centre
state: Nova Scotia
city: Toronto
country: Canada
facility: Toronto Memory Program (Neurology Research Inc.)
state: Ontario
city: Sherbrooke
country: Canada
facility: Novabyss Inc.
state: Quebec
Study officials:
affiliation: Sr. Clinical Scientist, Voyager Pharmaceutical
name: Connie Powers
role: PRINCIPAL_INVESTIGATOR
References:
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. doi: 10.1007/s00018-004-4386-y.
citation: 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. doi: 10.1159/000079125.
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. doi: 10.1074/jbc.M311993200. Epub 2004 Feb 9.
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. doi: 10.55782/ane-2004-1497.
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. doi: 10.1002/jnr.20028.