Alzheimer DiseasePhase 2LUCINDANCT03649724
The LUCINDA Trial: LeUprolide Plus Cholinesterase Inhibition to Reduce Neurological Decline in Alzheimer's
A Phase 2 study testing Eligard 22.5Mg Suspension for Injection in people with Alzheimer Disease and Mild Cognitive Impairment, run by Weill Medical College of Cornell University at 3 sites in United States.
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. Read more about this study
- Who is it for?
- Ages 60 to 120 years, women only
- Conditions the study is for
- Alzheimer Disease, Mild Cognitive Impairment
- What is being tested?
- Eligard 22.5Mg Suspension for Injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 86 participants
- Where
- 3 sitesUnited States
- Study dates
- 27 Nov 2020to 25 Jul 2026
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 60 to 120 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
3 sites in 1 country.
United States3 sites
University of Miami Miller School of Medicine
Boca Raton, Florida, 33433
University of Wisconsin - Madison
Madison, Wisconsin, 53792
Weill Medical College of Cornell University
New York, New York, 10021
About this study
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.
Read the 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.
- Conditions
- Alzheimer Disease, Mild Cognitive Impairment
- Being tested
- Placebo, Eligard 22.5Mg Suspension for Injection
- Medical subject headings
- Alzheimer Disease, Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
Placebo (0.25 ml normal saline) will be administered subcutaneously once every twelve weeks for 48 weeks.
Eligard 22.5Mg Suspension for InjectionDrug
Eligard 22.5Mg Suspension for Injection will be administered subcutaneously, in accord with manufacturer's direction, once every twelve weeks for 48 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | 0.25 ml of sterile normal saline administered subcutaneously / 12 weeks Receives: Drug: Placebo |
| Leuprolide | Experimental | Eligard 22.5mg administered subcutaneously / 12 weeks Receives: Drug: Eligard 22.5Mg Suspension for Injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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)
The ADCS-ADL assesses a subject's ability to perform activities of daily living such as eating, walking and bathing.
Measured: Baseline, 48 Weeks
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.
Measured: Baseline, 48 Weeks
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.
Measured: Baseline, 48 Weeks
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.
Measured: Baseline, 48 Weeks
Percent change in Neuropsychiatric Inventory (NPI)
The NPI measures behavioral and emotional symptoms of Alzheimer's Disease.
Measured: Baseline, 48 Weeks
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.
Measured: Baseline, 48 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Aug 2018
- Study start27 Nov 2020
- Primary completion25 Jul 2026
- Study completion25 Jul 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Alzheimer DiseaseStudies of the same condition, open and under way.
- More trials run by Weill Medical College of Cornell UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 86 participants (actual)
Sponsor and investigators
- Lead sponsor
- Weill Medical College of Cornell University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Aging (NIA), Tolmar Pharmaceuticals
- Responsible party
- Sponsor
- Investigators
- Tracy A Butler, MD, Principal investigator, Weill Medical College of Cornell UniversityJames E Galvin, MD, Principal investigator, University of MiamiCraig S Atwood, PhD, Principal investigator, University of Wisconsin, Madison
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03649724
- Sponsor's protocol ID
- 19-05020209
- Other IDs
- R01AG057681-01A1
- Acronym
- LUCINDA
- Status last verified
- Sep 2026
- First submitted
- 22 Aug 2018
- Last updated
- 21 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
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.
PubMed 34166841Butler 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.
PubMed 35922659Wickramasuriya 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.
PubMed 35809386Butler 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.
PubMed 39240636
Study at a glance
From the registry record, last updated by the sponsor on 21 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The LUCINDA Trial: LeUprolide Plus Cholinesterase Inhibition to Reduce Neurological Decline in Alzheimer's
- ClinicalTrials.gov ID
- NCT03649724
- Acronym / sponsor ID
- LUCINDA / 19-05020209
- Conditions
- Alzheimer Disease, Mild Cognitive Impairment
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 86 participants (actual)
- Lead sponsor
- Weill Medical College of Cornell UniversityUniversity, hospital or other
- Collaborators
- National Institute on Aging (NIA), Tolmar Pharmaceuticals
- Study start
- 27 Nov 2020 (actual)
- Primary completion
- 25 Jul 2026 (actual)
- Study completion
- 25 Jul 2026 (actual)
- First posted
- 28 Aug 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: Placebo0.25 ml of sterile normal saline administered subcutaneously / 12 weeks |
| Leuprolide | Experimental | Drug: Eligard 22.5Mg Suspension for InjectionEligard 22.5mg administered subcutaneously / 12 weeks |
Who may qualify
- Ages
- 60 to 120 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PlaceboPlacebo (0.25 ml normal saline) will be administered subcutaneously once every twelve weeks for 48 weeks. | Drug | Placebo |
| Eligard 22.5Mg Suspension for InjectionEligard 22.5Mg Suspension for Injection will be administered subcutaneously, in accord with manufacturer's direction, once every twelve weeks for 48 weeks. | Drug | Leuprolide |
Primary outcome
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.
6 secondary outcomes
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
Alzheimer Disease Cooperative Study Clinical Global Impression of Change (ADCS-CGIC+)
Time frame: Baseline, 48 Weeks
Percent change in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)
Time frame: Baseline, 48 Weeks
Percent change in Burden Inventory
Time frame: Baseline, 48 Weeks
Percent change in Neuropsychiatric Inventory (NPI)
Time frame: Baseline, 48 Weeks
Change in Brain Magnetic Resonance Imaging (MRI) biomarkers
Time frame: Baseline, 48 Weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Sep 2026.
- Background: PubMed 34166841Butler 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.
- Background: PubMed 35922659Butler 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.
- Background: PubMed 35809386Wickramasuriya 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.
- Background: PubMed 39240636Butler 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.
- LUCINDA websiteLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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.
Related trials for Alzheimer Disease
RecruitingPhase 2
Neuroplasticity Enhancement From Cognitive Training Reinforced by Psilocybin
Alzheimer's Disease
Not yet recruiting
Acupressure as Long-term Intervention to Slow the Progression of Early/Mild Alzheimer's Disease
Alzheimer's Disease
RecruitingObservational study
Effectiveness and Safety of Disease-Modifying Therapy for Alzheimer's Disease: A Multicenter Retrospective Study
Alzheimer's Disease (AD)
RecruitingPhase 3
A Phase 3 Study to Evaluate the Safety and Efficacy of KarXT + KarX-EC for the Treatment of Agitation Associated With Alzheimer's Disease (ADAGIO-1)
Alzheimer Disease
RecruitingPhase 3
A Study of Trontinemab in Cognitively Unimpaired Individuals at Risk for Progression to Symptomatic Alzheimer's Disease
Alzheimer's Disease
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tracy A Butler, MD principal investigator
Weill Medical College of Cornell University
James E Galvin, MD principal investigator
University of Miami
Craig S Atwood, PhD principal investigator
University of Wisconsin, Madison
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Eligard 22.5Mg Suspension for Injection in people with Alzheimer Disease and Mild Cognitive Impairment, run by Weill Medical College of Cornell University at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent change in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog-11) (time frame: Baseline, 48 Weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03649724, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Sep 2026.