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| ID | Type | Description | Link |
|---|---|---|---|
| R01AG057681-01A1 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute on Aging (NIA) | NIH |
| Tolmar Pharmaceuticals | UNKNOWN |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator | 0.25 ml of sterile normal saline administered subcutaneously / 12 weeks |
|
| Leuprolide | Experimental | Eligard 22.5mg administered subcutaneously / 12 weeks |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Placebo | Drug | Placebo (0.25 ml normal saline) will be administered subcutaneously once every twelve weeks for 48 weeks. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline, 48 Weeks |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline, 48 Weeks |
| Alzheimer Disease Cooperative Study Clinical Global Impression of Change (ADCS-CGIC+) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| 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 | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Miami Miller School of Medicine | Boca Raton | Florida | 33433 | United States | ||
| Weill Medical College of Cornell University |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34166841 | Background | 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. | |
| 35922659 | Background | 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. |
| Label | URL |
|---|---|
| LUCINDA website | View source |
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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.
Research data and results that document and support the study aims will be available after the final results are accepted for publication.
Approval from PI
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| ICF | No | No | Yes | Informed Consent Form | Feb 8, 2021 | Apr 4, 2021 |
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| Eligard 22.5Mg Suspension for Injection | Drug | Eligard 22.5Mg Suspension for Injection will be administered subcutaneously, in accord with manufacturer's direction, once every twelve weeks for 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. |
| 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. | 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. | Baseline, 48 Weeks |
| Percent change in Neuropsychiatric Inventory (NPI) | The NPI measures behavioral and emotional symptoms of Alzheimer's Disease. | 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. | Baseline, 48 Weeks |
| New York |
| New York |
| 10021 |
| United States |
| University of Wisconsin - Madison | Madison | Wisconsin | 53792 | United States |
| 35809386 | Background | 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. |
| 39240636 | Background | Butler 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. |
| ICF_001.pdf |
| ID | Term |
|---|---|
| D000544 | Alzheimer Disease |
| D060825 | Cognitive Dysfunction |
| ID | Term |
|---|---|
| D003704 | Dementia |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D024801 | Tauopathies |
| D019636 | Neurodegenerative Diseases |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
| D003072 | Cognition Disorders |
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| ID | Term |
|---|---|
| C493311 | luprolide acetate gel depot |
| D013535 | Suspensions |
| D007267 | Injections |
| ID | Term |
|---|---|
| D003102 | Colloids |
| D045424 | Complex Mixtures |
| D004304 | Dosage Forms |
| D004364 | Pharmaceutical Preparations |
| D004333 | Drug Administration Routes |
| D004358 | Drug Therapy |
| D013812 | Therapeutics |
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