The LUCINDA Trial: LeUprolide Plus Cholinesterase Inhibition to Reduce Neurological Decline in Alzheimer's

NCT ID: NCT03649724

Last Updated: 2025-08-01

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 180 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-11-27
• Study Completion Date: 2026-07-01

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.

Conditions

Alzheimer Disease; Mild Cognitive Impairment

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Placebo

0.25 ml of sterile normal saline administered subcutaneously / 12 weeks

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo (0.25 ml normal saline) will be administered subcutaneously once every twelve weeks for 48 weeks.

Leuprolide

Eligard 22.5mg administered subcutaneously / 12 weeks

Group Type: EXPERIMENTAL

Eligard 22.5Mg Suspension for Injection

Intervention Type: DRUG

Eligard 22.5Mg Suspension for Injection will be administered subcutaneously, in accord with manufacturer's direction, once every twelve weeks for 48 weeks.

Interventions

Placebo

Placebo (0.25 ml normal saline) will be administered subcutaneously once every twelve weeks for 48 weeks.

Intervention Type: DRUG

Eligard 22.5Mg Suspension for Injection

Eligard 22.5Mg Suspension for Injection will be administered subcutaneously, in accord with manufacturer's direction, once every twelve weeks for 48 weeks.

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 60 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

National Institute on Aging (NIA)

NIH

Sponsor Role: collaborator

Tolmar Pharmaceuticals

UNKNOWN

Sponsor Role: collaborator

Weill Medical College of Cornell University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Tracy A Butler, MD

Role: PRINCIPAL_INVESTIGATOR

Weill Medical College of Cornell University

James E Galvin, MD

Role: PRINCIPAL_INVESTIGATOR

University of Miami

Craig S Atwood, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Wisconsin, Madison

Locations

University of Miami Miller School of Medicine

Boca Raton, Florida, United States

Weill Medical College of Cornell University

New York, New York, United States

University of Wisconsin - Madison

Madison, Wisconsin, United States

Countries

United States

References

Butler T, Goldberg JD, Galvin JE, Maloney T, Ravdin L, Glodzik L, de Leon MJ, Hochman T, Bowen RL, Atwood CS. Rationale, study design and implementation of the LUCINDA Trial: Leuprolide plus Cholinesterase Inhibition to reduce Neurologic Decline in Alzheimer's. Contemp Clin Trials. 2021 Aug;107:106488. doi: 10.1016/j.cct.2021.106488. Epub 2021 Jun 22.

Reference Type: BACKGROUND

PMID: 34166841 (View on PubMed)

Butler T, Glodzik L, Wang XH, Xi K, Li Y, Pan H, Zhou L, Chiang GC, Morim S, Wickramasuriya N, Tanzi E, Maloney T, Harvey P, Mao X, Razlighi QR, Rusinek H, Shungu DC, de Leon M, Atwood CS, Mozley PD. Positron Emission Tomography reveals age-associated hypothalamic microglial activation in women. Sci Rep. 2022 Aug 3;12(1):13351. doi: 10.1038/s41598-022-17315-8.

Reference Type: BACKGROUND

PMID: 35922659 (View on PubMed)

Wickramasuriya N, Hawkins R, Atwood C, Butler T. The roles of GnRH in the human central nervous system. Horm Behav. 2022 Sep;145:105230. doi: 10.1016/j.yhbeh.2022.105230. Epub 2022 Jul 6.

Reference Type: BACKGROUND

PMID: 35809386 (View on PubMed)

Butler T, Tey SR, Galvin JE, Perry G, Bowen RL, Atwood CS. Endocrine Dyscrasia in the Etiology and Therapy of Alzheimer's Disease. J Alzheimers Dis. 2024;101(3):705-713. doi: 10.3233/JAD-240334.

Reference Type: BACKGROUND

PMID: 39240636 (View on PubMed)

Provided Documents

Document Type: Informed Consent Form

View Document

Related Links

https://jcto.weill.cornell.edu/lucinda

LUCINDA website

Other Identifiers

R01AG057681-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

19-05020209

Identifier Type: -

Identifier Source: org_study_id