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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03649724
Recruitment Status : Recruiting
First Posted : August 28, 2018
Last Update Posted : August 31, 2020
Sponsor:
Collaborator:
National Institute on Aging (NIA)
Information provided by (Responsible Party):
Weill Medical College of Cornell University

Brief Summary:
The LUCINDA Trial is a three-site, phase II, randomized, double-blind, placebo-controlled study of leuprolide acetate (Eligard) in women with 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. Our 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.

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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
Estimated Study Start Date : September 2020
Estimated Primary Completion Date : February 2025
Estimated Study Completion Date : February 2026


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.




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.



Information from the National Library of Medicine

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Ages Eligible for Study:   65 Years to 90 Years   (Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Female, post-menopausal
  • Probable 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)
  • MMSE 16-26 (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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03649724


Contacts
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Contact: Patrick Harvey, MA (646) 962-8508 pah2018@med.cornell.edu
Contact: Tom Maloney, PhD 646-962-8502 trm4001@med.cornell.edu

Locations
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United States, Florida
University of Miami Miller School of Medicine Not yet recruiting
Palm Beach Gardens, Florida, United States, 33410
Contact: Olena Mahneva, PhD         
Contact    305-243-6732      
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: Patrick Harvey, MA    646-962-8508    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)
Investigators
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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 2, 2020

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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    Key Record Dates
Last Update Posted: August 31, 2020
Last Verified: August 2020
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

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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:
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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