Antigonadotropin-Leuprolide in Alzheimer's Disease Drug INvestigation (ALADDIN) VP 104 Study
This study is currently recruiting patients.
Sponsored by: |
Voyager Pharmaceutical Corporation |
Information provided by: |
National Institute on Aging (NIA) |
Purpose
ALADDIN is a research study to investigate the safety and effectiveness of leuprolide (a hormone drug) to improve the cognitive
function and slow the progression of Alzheimer's disease (AD) in men 65 years and older with mild to moderate Alzheimer's
disease who reside in the community.
Condition
|
Treatment or Intervention |
Phase |
Alzheimer Disease
|
Drug: Leuprolide acetate
|
Phase II
|
MedlinePlus related topics: Alzheimer's Caregivers; Alzheimer's Disease
Genetics Home Reference related topics: Alzheimer disease
Study Type: Interventional
Study Design: Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Safety/Efficacy Study
Further Study Details:
Expected Total Enrollment:
90
Study start: December 2003;
Study completion: June 2005
ALADDIN is a clinical trial investigating the safety and effectiveness of leuprolide (a hormone drug) to improve the cognitive
function and slow the progression of Alzheimer's disease (AD). The study will include treatment of men 65 years and older
with mild to moderate Alzheimer's disease who reside in the community. The objective is to evaluate the safety and efficacy
of two different doses of leuprolide to improve the cognitive function and slow the progression of AD, as measured by the
ADAS-COG and the Clinical Global Impression (CGI). Measures of behavioral disturbances, and quality of life of the caregiver
will be made also. The study design is randomized, double blind, placebo-controlled, parallel group design with a 2:1 randomization
of drug to placebo. Sample size will include 90 participants from multiple test sites.
Following initial screening and baseline visits, the participant and caregiver will visit the site 8 times for a total of
10 visits over 48 months. The drug is administered via injection every 3 months. Safety assessments are completed and psychometric
testing is done. Participant's memory, behavior, and global functioning are assessed during the participant and caregiver
interviews. Each visit takes approximately 2 hours.
Eligibility
Ages Eligible for Study:
65 Years and above,
Genders Eligible for Study:
Male
Inclusion Criteria:
Patients who satisfy all of the inclusion criteria listed below will be eligible for entry into the trial.
- Patient and responsible caregiver can give their consent by signing the IRB-approved Informed Consent Form; or, when the patient
is judged by the Investigator to be unable to give consent, the legally authorized representative gives consent by signing
the consent form and the patient gives assent, in accord with local regulations;
- Male;
- 65 years of age or older;
- Diagnosis of probable AD according to the National Institute of Neurological Disorders-Alzheimer's Disease and Related Disorders
Association (NINDS-ADRDA) criteria, and the Investigator ascertains that the condition was present at least 6 months prior
to screening;
- Taking a drug for the treatment of AD, such as a cholinesterase inhibitor and/or Memantine®, which they began taking at least
90 days prior to baseline and, in the Investigator's opinion, the dosage will likely remain stable throughout the trial; or,
they have never taken such a drug or stopped taking it at least 90 days prior to baseline and will likely refrain from taking
such treatment throughout the trial;
- Taking other drugs or substances that have purported cognition-enhancing properties such as ginkgo biloba or Vitamin E, which
they began taking at least 60 days prior to baseline and, in the Investigator's opinion, the dosage will likely remain stable
throughout the trial; or, they have never taken such a drug or stopped taking it at least 90 days prior to baseline and will
likely refrain from taking such treatment throughout the trial;
- Mini Mental State Examination (MMSE) score of 12 to 24 (inclusive) at the screening visit;
- Brain imaging study (CT scan, MRI or PET) performed at the time of their initial diagnosis of AD or after that time, and the
findings were consistent with a diagnosis of probable AD, or, if a brain imaging study has not been performed, one will be
performed during the screening process;
- Rosen Modified Hachinski score of 4 or lower at the screening visit, supporting the Investigator's clinical judgment that
the patient's dementia is probable AD and not of vascular origin;
- Fluent in English or Spanish and completed at least 6 years of education;
- Live at home or in a congregate living facility for requirements other than skilled nursing care, and have a caregiver who
sees the patient at least three times a week for a total of at least 10 hours and can sign the consent form, provide information
pertinent to the patient's cognitive status, accompany the patient on clinic visits, and participate in the evaluations.
- Hamilton Depression Scale (17-item version) (HamD) score of 14 or less at the screening visit;
- DEXA scan, performed at screening, within normal limits (i.e., a T-score of greater than -2.0); or, if their DEXA measure
was abnormally low (i.e., a T-score of -2.0 or lower), in either a lumbar vertebra or hip, to specifically include a T-score
for the femoral neck), they were receiving treatment for osteoporosis/osteopenia for at least 3 weeks prior to baseline and
that treatment is not expected to change during the course of the trial; or, if their DEXA measure was abnormally low and
they are not receiving treatment for osteoporosis/osteopenia, they may proceed to baseline after 3 weeks of treatment for
osteoporosis/osteopenia provided that all inclusion/exclusion criteria are met, including assessment of the HamD, concomitant
medications, ECG and laboratory tests performed within 45 days of baseline show that they are eligible;
- Screening laboratory test values do not indicate significant medical conditions that would interfere with their participation
in and completion of the study.
Exclusion criteria:
Patients with any of the exclusion criteria listed below will be ineligible for entry into the study.
- Female;
- Younger than 65 years of age;
- Significant neurological disease affecting the brain or psychiatric disease other than AD, such as major depression, schizophrenia,
epilepsy, Parkinson's disease, or stroke;
- Current significant systemic illness or symptoms of organ failure;
- Screening ECG shows evidence of a serious and/or unstable condition or a recent (within 6 months) myocardial infarction as
determined by the Investigator;
- PSA test result exceeds 4.0 ng/mL;
- Receiving testosterone;
- Taking a drug for the treatment of AD for less than 90 days prior to baseline; or, in the opinion of the Investigator, they
are likely to either require a change in dose or discontinuation of the drug;
- Never received cholinesterase inhibitor treatment, and the likelihood of their starting such treatment during the study is
other than low, or they have taken and discontinued cholinesterase inhibitor treatment in the past and the likelihood of their
resuming cholinesterase inhibitor treatment during the study is other than low;
- Started or changed within 60 days prior to the screening visit the dosage of any drug (including OTC) that affects cognitive
function, such as neuroleptics, antidepressants, anxiolytics, sedatives, hypnotics, anti-convulsants, centrally acting antihypertensive
agents such as clonidine and Aldomet; or other medications that have been shown to have possible effects on cognition such
as Vitamin E, nonsteroidal anti-inflammatory drugs, and statins, or if, in the Investigator's opinion, the dosage of such
medication is likely to be changed during the course of this trial. Any changes in the dosage of any of these drugs during
the course of the trial and the reason for the change must be fully recorded in the concomitant medication page of the patient's
case report form (CRF). If a drug that affects cognition (e.g., a hypnotic or anxiolytic drug) is given on a PRN basis, such
treatment should be interrupted for 12 hours before a visit, if possible;
- Taking coumadin or anti-Parkinsonian medications;
- Have taken other investigational drugs within 30 days or 5 half-lives prior to randomization, whichever is longer;
- Taking other medications known to affect serum gonadotropin (Gn) concentrations, such as gosorelin or danazol;
- A screening HamD score of 15 or higher;
- Abuse or dependence on alcohol or other substances satisfies criteria for DSM-IV categories 303.9 or 305;
- Donated blood within 30 days of baseline or are likely to do so during the course of the trial;
- History of cancer, particularly breast cancer or known or suspected prostate cancer, within the last 5 years, except for basal
cell or squamous cell cancer of the skin;
- Clinically significant bladder outlet obstruction, in the judgment of the Investigator or designated examining physician;
- Abnormalities of the esophagus which delay esophageal emptying such as stricture or achalasia, or are unable to stand or sit
upright for at least 30 minutes;
- Sleep apnea.
Location
and Contact
Information
California Bay Area Research Institute, Lafayette,
California,
94549,
United States; Recruiting
Southwest Clinical Research, Rancho Mirage,
California,
92270,
United States; Recruiting
Margolin Brain Institute, Fresno,
California,
93720,
United States; Recruiting
David Margolin, MD
559-299-1515
dimmd@sbcglobal.net
David I. Margolin, MD, Principal Investigator
Connecticut Geriatric and Adult Psychiatry LLC, Hamden,
Connecticut,
06518,
United States; Recruiting
Florida Baumel-Eisner Neuromedical Institute, Ft. Lauderdale,
Florida,
33321,
United States; Recruiting
Baumel-Eisner Neuromedical Institute, Boca Raton,
Florida,
33486,
United States; Recruiting
Mery Lossada, MD
561-368-1123
Baumel-Eisner Neuromedical Institute, Miami Beach,
Florida,
33154,
United States; Recruiting
Beth Safirstein, MD
305-865-0063
Meridien Research, St. Petersburg,
Florida,
33710,
United States; Recruiting
Massachusetts Boston University School of Medicine, Boston,
Massachusetts,
02118-2526,
United States; Recruiting
South Carolina Medical University of South Carolina, Charleston,
South Carolina,
29406,
United States; Recruiting
Virginia Innovative Clinical Research Center, Alexandria,
Virginia,
22304,
United States; Recruiting
Chris Battle
703-212-5907
cbattle@icrc1.com
Stuart R. Stark, MD, Principal Investigator
Wisconsin Middleton VA Wisconsin Alzheimer's Institute, Madison,
Wisconsin,
53705,
United States; Recruiting
Study chairs or principal investigators
Richard L. Bowen, MD, Principal Investigator, Voyager Pharmaceutical Corporation
More Information
Publications
Bowen RL, Smith MA, Harris PL, Kubat Z, Martins RN, Castellani RJ, Perry G, Atwood CS. Elevated luteinizing hormone expression
colocalizes with neurons vulnerable to Alzheimer's disease pathology. J Neurosci Res. 2002 Nov 1;70(3):514-8.
Short RA, Bowen RL, O'Brien PC, Graff-Radford NR. Elevated gonadotropin levels in patients with Alzheimer disease. Mayo
Clin Proc. 2001 Sep;76(9):906-9.
Bowen RL, Isley JP, Atkinson RL. An association of elevated serum gonadotropin concentrations and Alzheimer disease? J Neuroendocrinol.
2000 Apr; 12(4): 351-4.
Study ID Numbers:
IA0051
Record last reviewed:
August 2004
Record first received:
January 22, 2004
ClinicalTrials.gov Identifier:
NCT00076440Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2004-10-29