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

Alzheimer Disease Clinical Trial

— LUCINDA  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03649724
• Other study ID #: 19-05020209
• Secondary ID: R01AG057681-01A1
• Status: Recruiting
• Phase: Phase 2
• Start date: November 27, 2020
• Est. completion date: February 2026

Study information

• Verified date: April 2024
• Source: Weill Medical College of Cornell University
• Contact: Sarah Khan
• Phone: 830-582-4632
• Email: skh4002[@]med.cornell.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 180
• Est. completion date: February 2026
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 60 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Alzheimer Disease
• Cognitive Dysfunction
• Mild Cognitive Impairment

Intervention

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

Locations

Country	Name	City	State
United States	University of Miami Miller School of Medicine	Boca Raton	Florida
United States	University of Wisconsin - Madison	Madison	Wisconsin
United States	Weill Medical College of Cornell University	New York	New York

Sponsors (3)

Lead Sponsor	Collaborator
Weill Medical College of Cornell University	National Institute on Aging (NIA), Tolmar Pharmaceuticals

Country where clinical trial is conducted

United States, 

References & Publications (3)

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Percent change in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-in Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL)	The ADCS-ADL assesses a subject's ability to perform activities of daily living such as eating, walking and bathing.	Baseline, 48 Weeks
Secondary	Alzheimer Disease Cooperative Study Clinical Global Impression of Change (ADCS-CGIC+)	The ADCS-CGIC+ uses structured interviews with the subject and his or her caregiver to determine whether there has been a change in the subject's overall level of functioning.	Baseline, 48 Weeks
Secondary	Percent change in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)	The RBANS is a set of tests that measures thinking abilities including memory, language and attention.	Baseline, 48 Weeks
Secondary	Percent change in Burden Inventory	The Burden Inventory is a questionnaire that assesses how people sometimes feel when they are taking care of another person.	Baseline, 48 Weeks
Secondary	Percent change in Neuropsychiatric Inventory (NPI)	The NPI measures behavioral and emotional symptoms of Alzheimer's Disease.	Baseline, 48 Weeks
Secondary	Change in Brain Magnetic Resonance Imaging (MRI) biomarkers	Percent change in volume of AD-related brain regions (hippocampi, ventricles) and hippocampal perfusion measured with Arterial Spin Labeling (ASL) will be assessed.	Baseline, 48 Weeks

External Links

•   LUCINDA website