The LUCINDA Trial: LeUprolide Plus Cholinesterase Inhibition to Reduce Neurological Decline in Alzheimer's
Trial Snapshot
- Phase
- Phase 2
- Status
- Active, not recruiting
- Enrollment
- 180
- Locations
- 6
- Primary Endpoint
- Percent change in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog-11)
Study Overview
Brief Summary
The LUCINDA Trial is a three-site, phase II, randomized, double-blind, placebo-controlled study of leuprolide acetate (Eligard) in women with Mild Cognitive Impairment or Alzheimer's Disease taking a stable dose of a cholinesterase inhibitor medication like donepezil. Its objective is to assess the efficacy of a 48-week regimen of leuprolide (22.5 mg per 12 weeks) compared to placebo on cognitive function, global function and plasma and neuroimaging biomarkers.
Detailed Description
This project aims to re-purpose the safe and well-tolerated gonadotropin-releasing hormone (GnRH) analogue Leuprolide Acetate for use in Alzheimer's Disease (AD). Leuprolide Acetate is currently used in adults for prostate cancer, endometriosis, uterine fibroids and in preparation for in-vitro fertilization, and in children for central precocious puberty. The purpose of this study to confirm and extend results from a prior phase II study (Bowen et al, 2015) which demonstrated that Leuprolide halted cognitive and functional decline in a subgroup of women with mild-moderate AD who were also taking the acetylcholinesterase inhibitor donepezil. Objectives are to replicate, in the same subgroup, Leuprolide's clinical EFFICACY in this prior trial and to add neuroimaging and plasma BIOMARKERS that will help elucidate Leuprolide's likely multiple mechanisms of action in AD. These mechanisms include decreasing levels of Luteinizing Hormone (LH) based on extensive preclinical evidence that decreasing LH preserves cognition and decreases amyloid deposition and tau phosphorylation in animal models of AD, as well as new evidence that GnRH analogues may have anti-inflammatory effects.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 60 Years to 120 Years (Adult, Older Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Female, post-menopausal
- •Probable AD or MCI due to AD according to NIA-AA criteria
- •Taking a stable dose of a cholinesterase inhibitor such as donepezil/Aricept and dosage likely to remain stable throughout the trial
- •MOCA > 11 or blind MOCA > 8 (inclusive) at screening visit
- •Hachinski score <5 supporting clinical judgment that dementia is not of vascular origin
- •Fluent in English
- •has a study partner / caregiver who interacts with the subject for at least 5 hours per week on average and can participate in evaluations
Exclusion Criteria
- •Presence based on exam, history or MRI of significant brain disease other than AD such as schizophrenia, epilepsy, Parkinson's disease or large territory stroke
- •Current substance abuse in accord with DSM V criteria
- •Significantly depressed (Geriatric Depression Scale > 10)
- •Physical or psychological MRI contraindications, or likely unable to tolerate neuroimaging
- •Taking other medications known to affect serum sex hormone or gonadotropin concentrations such as estrogen and/or progesterone for hormone replacement therapy, goserelin or danazol
- •Presence of significant systemic illness likely to interfere with participation in or completion of the study or to affect study results such as cancer within 5 years (other than non-melanoma skin cancer), autoimmune disease, recent myocardial infarction, signs/symptoms of organ failure based on history, ECG, screening laboratory and/or physical exams
- •Receiving other investigational drugs within 30 days or 5 half-lives prior to randomization, whichever is longer
Arms & Interventions
Placebo
0.25 ml of sterile normal saline administered subcutaneously / 12 weeks
Intervention: Placebo (Drug)
Leuprolide
Eligard 22.5mg administered subcutaneously / 12 weeks
Intervention: Eligard 22.5Mg Suspension for Injection (Drug)
Outcomes
Primary Outcomes
Percent change in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog-11)
Time Frame: Baseline, 48 Weeks
The ADAS-cog-11 consists of 11 tasks measuring the disturbances of memory, language, praxis, attention and other cognitive abilities which are often referred to as the core symptoms of Alzheimer's Disease.
Secondary Outcomes
- Percent change in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-in Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL)(Baseline, 48 Weeks)
- Change in Brain Magnetic Resonance Imaging (MRI) biomarkers(Baseline, 48 Weeks)
- Percent change in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)(Baseline, 48 Weeks)
- Percent change in Burden Inventory(Baseline, 48 Weeks)
- Percent change in Neuropsychiatric Inventory (NPI)(Baseline, 48 Weeks)
- Alzheimer Disease Cooperative Study Clinical Global Impression of Change (ADCS-CGIC+)(Baseline, 48 Weeks)