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

Primary Purpose

Alzheimer Disease, Mild Cognitive Impairment

Status

Recruiting

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Placebo

Eligard 22.5Mg Suspension for Injection

About this trial

This is an interventional treatment trial for Alzheimer Disease

Eligibility Criteria

65 Years - 120 Years (Older Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

University of Miami Miller School of MedicineRecruiting
Weill Medical College of Cornell UniversityRecruiting
University of Wisconsin - MadisonRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Placebo

Leuprolide

Arm Description

0.25 ml of sterile normal saline administered subcutaneously / 12 weeks

Eligard 22.5mg administered subcutaneously / 12 weeks

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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.

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.

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.

Percent change in Neuropsychiatric Inventory (NPI)

The NPI measures behavioral and emotional symptoms of Alzheimer's Disease.

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.

Full Information

NCT ID

NCT03649724

First Posted

August 22, 2018

Last Updated

May 30, 2023

Sponsor

Weill Medical College of Cornell University

Collaborators

National Institute on Aging (NIA), Tolmar Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT03649724

Brief Title

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

Acronym

LUCINDA

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

May 2023

Overall Recruitment Status

Recruiting

Study Start Date

November 27, 2020 (Actual)

Primary Completion Date

February 2025 (Anticipated)

Study Completion Date

February 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Weill Medical College of Cornell University

Collaborators

National Institute on Aging (NIA), Tolmar Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. 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 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Alzheimer Disease, Mild Cognitive Impairment

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

180 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

0.25 ml of sterile normal saline administered subcutaneously / 12 weeks

Arm Title

Leuprolide

Arm Type

Experimental

Arm Description

Eligard 22.5mg administered subcutaneously / 12 weeks

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Eligard 22.5Mg Suspension for Injection

Intervention Description

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 Measure Information:

Title

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

Description

Time Frame

Baseline, 48 Weeks

Secondary Outcome Measure Information:

Title

Percent change in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-in Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL)

Description

The ADCS-ADL assesses a subject's ability to perform activities of daily living such as eating, walking and bathing.

Time Frame

Baseline, 48 Weeks

Title

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

Description

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.

Time Frame

Baseline, 48 Weeks

Title

Percent change in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)

Description

The RBANS is a set of tests that measures thinking abilities including memory, language and attention.

Time Frame

Baseline, 48 Weeks

Title

Percent change in Burden Inventory

Description

The Burden Inventory is a questionnaire that assesses how people sometimes feel when they are taking care of another person.

Time Frame

Baseline, 48 Weeks

Title

Percent change in Neuropsychiatric Inventory (NPI)

Description

The NPI measures behavioral and emotional symptoms of Alzheimer's Disease.

Time Frame

Baseline, 48 Weeks

Title

Change in Brain Magnetic Resonance Imaging (MRI) biomarkers

Description

Percent change in volume of AD-related brain regions (hippocampi, ventricles) and hippocampal perfusion measured with Arterial Spin Labeling (ASL) will be assessed.

Time Frame

Baseline, 48 Weeks

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

65 Years

Maximum Age & Unit of Time

120 Years

Accepts Healthy Volunteers

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 Ever treated with active or passive immunization for AD (e.g. Lecanemab) due to unknown alterations in systemic and brain inflammation, which may confound results

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Sarah Khan

Phone

830-582-4632

skh4002@med.cornell.edu

First Name & Middle Initial & Last Name or Official Title & Degree

Tom Maloney, PhD

Phone

646-962-8502

trm4001@med.cornell.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Tracy A Butler, MD

Organizational Affiliation

Weill Medical College of Cornell University

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

James E Galvin, MD

Organizational Affiliation

University of Miami

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Craig S Atwood, PhD

Organizational Affiliation

University of Wisconsin, Madison

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Miami Miller School of Medicine

City

Boca Raton

State/Province

Florida

ZIP/Postal Code

33433

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Adolfo M Henriquez, MA

Phone

561-869-6820

amh122@miami.edu

First Name & Middle Initial & Last Name & Degree

James E Galvin, MD

Facility Name

Weill Medical College of Cornell University

City

New York

State/Province

New York

ZIP/Postal Code

10021

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Sarah Khan

Phone

830-582-4632

skh4002@med.cornell.edu

First Name & Middle Initial & Last Name & Degree

Patrick Harvey, MA

Phone

830-582-4632

lucinda@med.cornell.edu

First Name & Middle Initial & Last Name & Degree

Tracy A Butler, MD

Facility Name

University of Wisconsin - Madison

City

Madison

State/Province

Wisconsin

ZIP/Postal Code

53792

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Maggie Chilsen

Phone

608-263-2704

mchilsen@clinicaltrials.wisc.edu

First Name & Middle Initial & Last Name & Degree

Craig S Atwood, PhD

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing 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.

IPD Sharing Time Frame

Research data and results that document and support the study aims will be available after the final results are accepted for publication.

IPD Sharing Access Criteria

Approval from PI

Citations:

PubMed Identifier

34166841

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.

Results Reference

background

PubMed Identifier

35922659

Citation

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.

Results Reference

background

PubMed Identifier

35809386

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.

Results Reference

background

Links:

URL

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

Description

LUCINDA website

Learn more about this trial

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

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