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 women leuprolide is commonly used to treat hormone related conditions such
as endometriosis and uterine fibroids. The study will include treatment of women 65 years
and older with mild to moderate Alzheimer's disease who reside in the community.
Minimum age: 65 Years.
Maximum age: N/A.
Gender(s): Female.
Inclusion Criteria:
Patients who satisfy all of the inclusion criteria listed below will be eligible for entry
into the trial. Patients will be considered eligible if:
- They give their consent by signing the IRB-approved Informed Consent Form and the
responsible caregiver also signs the consent form; or, if the patient is judged by
the Investigator to be unable to give consent, if the legally authorized
representative gives consent by signing the consent form and the patient gives
assent, in accord with local regulations;
- They are female;
- They are 65 years of age or older;
- They have a 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;
- They are taking a cholinesterase inhibitor, they began taking it at least 90 days
prior to baseline and, in the Investigator's opinion, the dosage will likely remain
stable throughout the trial;
- They are taking other drugs or substances that have purported cognition enhancing
properties such as ginkgo biloba and Vitamin E, they began taking it at least 60 days
prior to baseline and, in the Investigator's opinion, the dosage will likely remain
stable throughout the trial;
- They score no lower than 12 or higher than 24 on the (MMSE) administered at the
screening visit;
- They have had a 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;
- Their Rosen Modified Hachinski score was 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;
- They are fluent in English or Spanish and completed at least 6 years of education;
- They 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 time 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;
- Their hormone replacement therapy (HRT), if any, has been stable for at least 60 days
prior to baseline, and is not expected to change during the course of the trial;
- They score less than 15 on the Hamilton Depression Scale (17-item version) (HamD)
administered as part of the screening evaluation;
- Absorptiometry (dual-energy x-ray absorpometry (DEXA) scan), performed at screening,
was within normal limits (i. e., a T- score of no less than - 2. 0); or, if their DEXA
measure was abnormally low, they were receiving treatment for osteoporosis for at
least 3 weeks 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, they may enter the trial after 3 weeks of treatment
provided that assessments of the HamD, concomitant medications, ECG tracing and
laboratory tests performed within 45 days of baseline show that they are eligible.
- values on their screening laboratory tests 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. Patients will be declared ineligible if:
- They are male;
- They are younger than 65 years of age;
- They have significant neurological disease affecting the brain or psychiatric disease
other than AD, such as major depression, schizophrenia, epilepsy, Parkinson's
disease, or stroke;
- They have current significant systemic illness or symptoms of organ failure;
- The screening ECG shows evidence of a serious and/or unstable condition or a recent
(within 6 months) myocardial infarction;
- They have a history of cancer within the last 5 years, except for basal cell or
squamous cell cancer, or cervical carcinoma in situ;
- They are taking a cholinesterase inhibitor (tacrine, donepezil, rivastigmine, or
galantamine) 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
- They have never received cholinesterase inhibitor treatment and are likely to
initiate it;
- They started or changed within 60 days prior to the screening visit the dosage of any
drug (including an over the counter drug) 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, non steroidal anti-inflammatory drugs, statins, and hormone replacement
therapy, 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 is given on a PRN basis, such treatment
should be interrupted for 12 hours before a visit, it at all possible;
- They are receiving coumadin or anti-Parkinsonian medications;
- They have received other investigational drugs within 30 days or 5 half-lives prior
to randomization, whichever is longer;
- They are taking other medications known to affect serum gonadotropin (Gn)
concentrations, such as goserelin or danazol, except for estrogen and/or
progesterone;
- They have a history of bone fracture possibly secondary to low bone mass density;
- They have a history of osteoporosis not associated with bone fracture unless they are
receiving therapy for osteoporosis for at least 3 weeks, and the treatment regimen is
expected to stay stable their DEXA measures were abnormally low (i. e., T-score <-2. 0)
and they were not receiving treatment for osteoporosis for at least 3 weeks;
- They have a screening HamD score of 15 or higher;
- Their abuse or dependence on alcohol or other substances satisfy criteria for DSM-IV
categories 303. 9 or 305; or
- They have donated blood within 30 days of baseline or are likely to do so during the
course of the trial.
Smith MA, Perry G, Atwood CS, Bowen RL. Estrogen replacement and risk of Alzheimer disease. JAMA. 2003 Mar 5;289(9):1100; author reply 1101-2.
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.