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

• ClinicalTrials.gov Identifier: NCT03649724
• Recruitment Status: Recruiting
• First Posted: August 28, 2018
• Last Update Posted: August 2, 2021
• Sponsor: Weill Medical College of Cornell University
• Collaborators: National Institute on Aging (NIA); Tolmar Pharmaceuticals
• Information provided by (Responsible Party): Weill Medical College of Cornell University

Study Description

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 donepezil (Aricept.) 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.

Condition or disease	Intervention/treatment	Phase
Alzheimer Disease; Mild Cognitive Impairment	Drug: Placebo; Drug: Eligard 22.5Mg Suspension for Injection	Phase 2

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 (Clinical Trial)
• Estimated Enrollment: 180 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: The LUCINDA Trial: LeUprolide Plus Cholinesterase Inhibition to Reduce Neurological Decline in Alzheimer's
• Actual Study Start Date: November 27, 2020
• Estimated Primary Completion Date: February 2025
• Estimated Study Completion Date: February 2026

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Placebo; 0.25 ml of sterile normal saline administered subcutaneously / 12 weeks	Drug: Placebo; Placebo (0.25 ml normal saline) will be administered subcutaneously once every twelve weeks for 48 weeks.
Experimental: Leuprolide; Eligard 22.5mg administered subcutaneously / 12 weeks	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.

Outcome Measures

Primary Outcome Measures :

1. 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 Outcome Measures :

1. Percent change in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-in Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) [ Time Frame: Baseline, 48 Weeks ]
   The ADCS-ADL assesses a subject's ability to perform activities of daily living such as eating, walking and bathing.
2. Alzheimer Disease Cooperative Study Clinical Global Impression of Change (ADCS-CGIC+) [ Time Frame: Baseline, 48 Weeks ]
   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.
3. Percent change in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) [ Time Frame: Baseline, 48 Weeks ]
   The RBANS is a set of tests that measures thinking abilities including memory, language and attention.
4. Percent change in Burden Inventory [ Time Frame: Baseline, 48 Weeks ]
   The Burden Inventory is a questionnaire that assesses how people sometimes feel when they are taking care of another person.
5. Percent change in Neuropsychiatric Inventory (NPI) [ Time Frame: Baseline, 48 Weeks ]
   The NPI measures behavioral and emotional symptoms of Alzheimer's Disease.
6. Change in Brain Magnetic Resonance Imaging (MRI) biomarkers [ Time Frame: Baseline, 48 Weeks ]
   Percent change in volume of AD-related brain regions (hippocampi, ventricles) and hippocampal perfusion measured with Arterial Spin Labeling (ASL) will be assessed.

Eligibility Criteria

• Ages Eligible for Study: 65 Years to 120 Years (Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Female, post-menopausal
• Probable AD or MCI due to AD according to NIA-AA criteria
• Taking a stable dose of donepezil (Aricept) for at least 90 days prior to baseline, and dosage likely to remain stable throughout the trial
• not taking memantine (Namenda)
• 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
• Living at home or in a facility other than a nursing home with a caregiver who sees the patient at least three times a week for a total of at least 10 hours and can sign the consent form, accompany the patient on clinic visits, and 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
• Ever treated with active or passive immunization as part of a different clinical trial for AD due to unknown alterations in systemic and brain inflammation, which may confound results

Contacts and Locations

Contacts

Contact: Sarah Khan; 830-582-4632; skh4002@med.cornell.edu

Contact: Tom Maloney, PhD; 646-962-8502; trm4001@med.cornell.edu

Locations

United States, Florida

University of Miami Miller School of Medicine; Not yet recruiting

Palm Beach Gardens, Florida, United States, 33410

Contact: Susan Rawn, RN sxr3381@med.miami.edu

Principal Investigator: James E Galvin, MD

United States, New York

Weill Medical College of Cornell University; Recruiting

New York, New York, United States, 10021

Contact: Sarah Khan 830-582-4632 skh4002@med.cornell.edu

Contact: Patrick Harvey, MA 830-582-4632 pah2018@med.cornell.edu

Principal Investigator: Tracy A Butler, MD

United States, Wisconsin

University of Wisconsin - Madison; Not yet recruiting

Madison, Wisconsin, United States, 53792

Contact: Rebecca Kintner 608-262-3456 rkintner@clinicaltrials.wisc.edu

Principal Investigator: Craig S Atwood, PhD

Sponsors and Collaborators

Weill Medical College of Cornell University

National Institute on Aging (NIA)

Tolmar Pharmaceuticals

Investigators

• Principal Investigator: 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

  Study Documents (Full-Text)

Documents provided by Weill Medical College of Cornell University:

Informed Consent Form  [PDF] February 8, 2021

More Information

• Responsible Party: Weill Medical College of Cornell University
• ClinicalTrials.gov Identifier: NCT03649724
• Other Study ID Numbers: 19-05020209; R01AG057681-01A1 ( U.S. NIH Grant/Contract )
• First Posted: August 28, 2018
• Last Update Posted: August 2, 2021
• Last Verified: July 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes

Plan Description

The data and resources sharing plan for this project is in accordance with both Weill Cornell and NIH Data Sharing Policies. All raw clinical, genetic, and imaging data from this project will be available upon written request. Deidentified neuroimaging data may be uploaded to one or more of several available data sharing sites designed for this purpose. The final data will be available in acceptable formats such as presentations and publications.

Research data and results that document and support the study aims will be available after the final results are accepted for publication. The data to be shared will be anonymized and there will be no fees or other restrictions.

• Supporting Materials: Study Protocol; Informed Consent Form (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

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:

Alzheimer Disease; Cognitive Dysfunction; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Cognition Disorders; Leuprolide; Fertility Agents, Female; Fertility Agents; Reproductive Control Agents; Physiological Effects of Drugs; Antineoplastic Agents, Hormonal; Antineoplastic Agents