Leuprolide for Alzheimer's Disease

(LUCINDA Trial)

Recruiting at 3 trial locations

Overseen By James E Galvin, MD

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Weill Medical College of Cornell University

Must be taking: Cholinesterase inhibitors

Must not be taking: Estrogen, Progesterone, Goserelin, Danazol

Disqualifiers: Schizophrenia, Epilepsy, Parkinson's, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 48 weeks

180 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial requires participants to continue taking a stable dose of a cholinesterase inhibitor medication like donepezil. However, you cannot take medications that affect hormone levels, such as estrogen or progesterone.

How does the drug Leuprolide acetate differ from other Alzheimer's treatments?

Leuprolide acetate, typically used for conditions like prostate cancer, is unique for Alzheimer's treatment as it is a hormone therapy that works by affecting hormone levels, unlike other Alzheimer's drugs that target amyloid plaques or enhance brain function. ^{1 2 3 4 5}

Research Team

Craig S Atwood, PhD

Principal Investigator

University of Wisconsin, Madison

James E Galvin, MD

Principal Investigator

University of Miami

Tracy A Butler, MD

Principal Investigator

Weill Medical College of Cornell University

Eligibility Criteria

The LUCINDA Trial is for post-menopausal women fluent in English with Mild Cognitive Impairment or Alzheimer's Disease, already taking a stable dose of cholinesterase inhibitors like donepezil. Participants must have a caregiver and meet specific cognitive criteria without significant brain disease other than AD, recent substance abuse, or serious systemic illness.

Inclusion Criteria

Has a study partner / caregiver who interacts with the subject for at least 5 hours per week on average and can participate in evaluations

I have been diagnosed with Alzheimer's disease or mild cognitive impairment due to Alzheimer's.

I am a woman and have gone through menopause.

Exclusion Criteria

Receiving other investigational drugs within 30 days or 5 half-lives prior to randomization, whichever is longer

I have never been immunized for Alzheimer's disease.

I do not have any major illnesses that could affect my participation in the study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive leuprolide acetate or placebo every 12 weeks for a total of 48 weeks

48 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Leuprolide acetate (Eligard)
• Placebo

Trial Overview This trial tests the effect of leuprolide acetate (Eligard) on cognitive function in women with Alzheimer's or MCI over 48 weeks. It compares Eligard injections every 12 weeks against placebo while participants continue their usual cholinesterase inhibitor medication.

Participant Groups

Group I: Leuprolide Experimental Treatment 1 Intervention

Eligard 22.5mg administered subcutaneously / 12 weeks

Group II: Placebo Placebo Group 1 Intervention

0.25 ml of sterile normal saline administered subcutaneously / 12 weeks

Leuprolide acetate (Eligard) is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Lupron for:

• Prostate cancer
• Endometriosis
• Precocious puberty

Approved in European Union as Lupron for:

• Prostate cancer
• Endometriosis
• Precocious puberty
• Uterine fibroids

Approved in Canada as Lupron for:

• Prostate cancer
• Endometriosis
• Precocious puberty

Who Is Running the Clinical Trial?

Weill Medical College of Cornell University

Lead Sponsor

Trials

1,103

Recruited

1,157,000+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Tolmar Pharmaceuticals

Collaborator

Trials

1

Recruited

180+

Findings from Research

Lecanemab and aducanumab are the first drugs approved by the FDA in 2023 that have disease-modifying effects for Alzheimer's disease, moving beyond just symptomatic treatment.

Lecanemab has demonstrated efficacy in clinical trials, showing potential to improve cognitive function in patients with Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

From Symptomatic Treatment to Disease Modification: A Turning Point in Alzheimer's Disease Management. Sheikh, M., Khan, SJ., Butt, HAT., et al.[2023]

Semaglutide has shown potential protective effects against Alzheimer's disease by enhancing autophagy and inhibiting apoptosis in SH-SY5Y cells treated with Aβ25-35, a model for Alzheimer's.

The study found that semaglutide increased levels of autophagy-related proteins (like LC3II and Beclin-1) and decreased apoptosis-related proteins (like Bax), suggesting a mechanism through which it may help protect against neurodegeneration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semaglutide-mediated protection against Aβ correlated with enhancement of autophagy and inhibition of apotosis. Chang, YF., Zhang, D., Hu, WM., et al.[2021]

In a study of 153 patients visiting pharmacies in Lithuania, 34.6% reported cognitive failures, with significant correlations found between these failures and age, particularly in memory performance.

The overall use of anti-dementia drugs slightly decreased from 2006 to 2011, while costs increased, indicating a trend towards higher spending on medications like nicergoline, despite deviations from established treatment guidelines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive failure evaluation and therapy based on pharmacy practice - utilization of anti-dementia drugs and food supplements in Lithuania. Vebraite, E., Morkuniene, V., Petrikonis, K., et al.[2016]

Lecanemab (Leqembi) was approved by the FDA for treating Alzheimer's dementia, showing a reduction in brain amyloid and a slowing of cognitive decline in clinical trials.

However, in an 18-month trial, lecanemab did not slow cognitive decline in women and actually worsened decline in participants with two APOE4 genes, raising concerns about its efficacy, especially since a significant portion of Alzheimer's patients carry this gene.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lecanemab (Leqembi) is not the right drug for patients with Alzheimer's disease. Kurkinen, M.[2023]

Lecanemab has shown promise in treating early Alzheimer's disease, demonstrating a significant reduction in clinical decline among participants in the study.

The study involved a large cohort, providing robust evidence for lecanemab's efficacy, although specific details on the number of subjects and duration were not provided in the overview.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evidence for lecanemab in early Alzheimer's disease. [2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

From Symptomatic Treatment to Disease Modification: A Turning Point in Alzheimer's Disease Management. [2023]

2. Scotland pubmed.ncbi.nlm.nih.gov

Semaglutide-mediated protection against Aβ correlated with enhancement of autophagy and inhibition of apotosis. [2021]

3. Germany pubmed.ncbi.nlm.nih.gov

Cognitive failure evaluation and therapy based on pharmacy practice - utilization of anti-dementia drugs and food supplements in Lithuania. [2016]

4. Poland pubmed.ncbi.nlm.nih.gov

Lecanemab (Leqembi) is not the right drug for patients with Alzheimer's disease. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Evidence for lecanemab in early Alzheimer's disease. [2023]