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

NCT03649724 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 19-05020209R01AG057681-01A1
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 3

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.

Conditions

Alzheimer Disease; Mild Cognitive Impairment

Outcome Measures

Primary Outcomes (1)

• Percent change in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog-11)

  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.

  Baseline, 48 Weeks

Secondary Outcomes (6)

• 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

• Alzheimer Disease Cooperative Study Clinical Global Impression of Change (ADCS-CGIC+)

  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

Study Arms (2)

Placebo

PLACEBO COMPARATOR

0.25 ml of sterile normal saline administered subcutaneously / 12 weeks

Drug: Placebo

Leuprolide

EXPERIMENTAL

Eligard 22.5mg administered subcutaneously / 12 weeks

Drug: Eligard 22.5Mg Suspension for Injection

Interventions

Placebo DRUG

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

Placebo

Eligard 22.5Mg Suspension for Injection DRUG

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

Leuprolide

Eligibility Criteria

• Age: 60 Years - 120 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead
• National Institute on Aging (NIA): collaborator
• Tolmar Pharmaceuticals: collaborator

Study Sites (3)

University of Miami Miller School of Medicine

Boca Raton, Florida, 33433, United States

Location

Weill Medical College of Cornell University

New York, New York, 10021, United States

Location

University of Wisconsin - Madison

Madison, Wisconsin, 53792, United States

Location

Related Publications (4)

• 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.

  PMID: 34166841 BACKGROUND

• 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.

  PMID: 35922659 BACKGROUND

• 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.

  PMID: 35809386 BACKGROUND

• 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.

  PMID: 39240636 BACKGROUND

Related Links

• LUCINDA website

MeSH Terms

Conditions

Alzheimer Disease; Cognitive Dysfunction

Interventions

luprolide acetate gel depot; Suspensions; Injections

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Cognition Disorders

Intervention Hierarchy (Ancestors)

Colloids; Complex Mixtures; Dosage Forms; Pharmaceutical Preparations; Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Tracy A Butler, MD

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

• James E Galvin, MD

  University of Miami

  PRINCIPAL INVESTIGATOR

• Craig S Atwood, PhD

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 22, 2018
• First Posted: August 28, 2018
• Study Start: November 27, 2020
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2026
• Last Updated: August 1, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: Research data and results that document and support the study aims will be available after the final results are accepted for publication.
• Access Criteria: Approval from PI

Locations

US (3)