Leuprolide for Alzheimer's Disease

(LUCINDA Trial)

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called leuprolide (also known as Eligard) to determine its effectiveness for women with Mild Cognitive Impairment or Alzheimer's Disease who are already taking medications like donepezil. Researchers aim to discover if leuprolide can enhance thinking skills, daily functioning, and certain health markers in the blood and brain over a 48-week period. Participants will receive either leuprolide or a placebo (a non-active substance) to compare effects. Women who are post-menopausal, have Alzheimer's or mild memory issues, and are on a steady dose of a cholinesterase inhibitor might be suitable for the trial. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that leuprolide acetate (Eligard) is likely to be safe for humans?

Research has shown that leuprolide acetate has been studied for safety in women with Alzheimer's disease. In one study, women already taking cholinesterase inhibitors, medications for memory and thinking, received leuprolide. The study found that leuprolide was well-tolerated and helped maintain cognitive abilities, indicating no significant harmful side effects.

Another study found that combining leuprolide with donepezil, another Alzheimer's drug, successfully slowed memory and thinking decline without major safety concerns. While every treatment can have side effects, evidence suggests that leuprolide is generally well-tolerated in these situations. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Alzheimer's?

Most treatments for Alzheimer's disease, like donepezil or memantine, work by addressing symptoms such as memory loss and confusion. However, leuprolide acetate, commonly known as Eligard, is unique because it targets hormonal pathways by modulating the effects of hormones that might influence Alzheimer's progression. This approach offers a fresh perspective on managing Alzheimer's, aiming to slow down the disease's progression rather than just alleviating symptoms. Researchers are excited about Eligard because it could potentially open new avenues for treatment, providing hope for a more effective way to tackle this challenging condition.

What evidence suggests that leuprolide might be an effective treatment for Alzheimer's?

Research suggests that leuprolide acetate, which participants in this trial may receive, might help slow Alzheimer's disease. Studies have shown that using leuprolide with drugs like donepezil can help maintain mental abilities. In one study, patients taking leuprolide experienced a slower decline in thinking and daily activities compared to those not taking it. The combination of leuprolide and cholinesterase inhibitors, such as donepezil, has been linked to stopping or slowing the worsening of symptoms. This indicates that leuprolide could be a helpful treatment option for women with Alzheimer's. ^{1 2 4 5 6}

Who Is on the Research Team?

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

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/25310993/

Lupron Depot for Alzheimer's: Preserving Cognitive Function To test the efficacy and safety of leuprolide acetate (Lupron Depot) in the treatment of Alzheimer's disease (AD), we conducted a 48-week, double-blind ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8550816/

Leuprolide plus cholinesterase inhibition to reduce ... Basic biological, epidemiological and clinical trial data suggest leuprolide acetate mediates improvement and stabilization of neuropathology and cognitive ...

3. journals.sagepub.com journals.sagepub.com/doi/10.3233/JAD-141626

A Clinical Study of Lupron Depot in the Treatment ... These data indicate that cognitive function is preserved in patients treated with high dose Lupron who were already using AChEIs. The positive interaction ...

4. neurologyadvisor.com neurologyadvisor.com/features/leuprolide-acetate-potential-treatment-for-alzheimer-disease-in-women/

Leuprolide Acetate: Alzheimer's Treatment for Women A phase 2 study by Bowen et al has indicated that leuprolide slowed functional and cognitive decline in a group of women with mild to moderate AD also ...

5. adrc.wisc.edu adrc.wisc.edu/news/uw-study-examines-potential-treatment-alzheimers-disease

UW study examines potential treatment for Alzheimer's disease Using leuprolide and donepezil together during that clinical trial successfully halted cognitive decline and was correlated with research ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S155171442100224X

Rationale, study design and implementation of the ... The LUCINDA trial is a three site, randomized, placebo-controlled double-blind study to assess the effect of a 48-week regimen of leuprolide acetate (Eligard, ...