Predicting Cognitive Decline From Androgen Deprivation Therapy

NCT05820932 | Active Not Recruiting DMC

• 2 other identifiers: 22806NCI-2023-02192
• Study Type: observational
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

Androgen Deprivation Therapy (ADT) is associated with cognitive impairment and dementia in men with prostate cancer. Pre-clinical data suggest that ADT-induced hypogonadism leads to accumulation of beta-amyloid plaques in the hippocampus, a pathological hallmark of Alzheimer's Disease (AD). Neuroimaging Functional magnetic resonance imaging (fMRI) studies also demonstrate that ADT decreases metabolic activity in the parietal, occipital, and prefrontal cortices. Multiple prospective cohort and population-based clinical studies have been conducted to test the association between ADT and cognitive impairment and/or dementia. Plasma biomarkers have been developed to predict brain amyloidosis, a key pathological feature of AD and a risk factor for developing dementia due to AD. The advantage of a blood-based assay is the lower cost, invasiveness, and time compared to cerebrospinal fluid (CSF) and Positron Emission Tomography (PET)-based biomarkers.

Conditions

Prostate Cancer

Keywords

Cognitive decline; Cognitive functioning

Outcome Measures

Primary Outcomes (3)

• Proportion of participants with cognitive decline (ADT cohort)

  Proportion with cognitive decline, defined as a decrease in \>=1 neurocognitive test after ADT by \>=1 standard deviation (SD) compared to baseline.

  Up to 12 months

• Mean cognitive decline (ADT cohort)

  The Z-scores of each cognitive test after receiving ADT will be calculated as a repeated measure.

  Up to 12 months

• Proportion of participants with cognitive impairment after ADT (ADT Cohort)

  Proportion of participants with cognitive impairment after receiving ADT, defined as a score of \>=1 SD below normative mean score (i.e., PC control) in \>=1 of the neurocognitive tests given during the course of ADT therapy.

  Up to 12 months

Secondary Outcomes (3)

• Change in mean plasma Aβ42/40 ratio

  Up to 12 months

• Mean cognition score

  Up to 12 months

• Mean study partner-reported cognition score

  Up to 12 months

Study Arms (3)

Participants with prostate cancer, ADT (ADT Cohort)

This group is comprised of adult men with hormone-sensitive prostate cancer who are starting androgen deprivation therapy as part of standard of care prostate cancer (not as part of this protocol).

Genetic: Blood-based assay; Diagnostic Test: Cognitive assessments; Other: Quality of Life Surveys

Participants in remission, No ADT (Prostate cancer Control (PC) Cohort))

This group is comprised of adult men who are in remission from prostate cancer who have never received ADT.

Genetic: Blood-based assay; Diagnostic Test: Cognitive assessments; Other: Quality of Life Surveys

Partners of Participants

Study partner participants will also be recruited

Other: Quality of Life Surveys

Interventions

Cognitive assessments DIAGNOSTIC_TEST

Cognitive assessments will be both participant- and partner-reported

Participants in remission, No ADT (Prostate cancer Control (PC) Cohort)); Participants with prostate cancer, ADT (ADT Cohort)

Blood-based assay GENETIC

Blood samples will be collected

Participants in remission, No ADT (Prostate cancer Control (PC) Cohort)); Participants with prostate cancer, ADT (ADT Cohort)

Quality of Life Surveys OTHER

Participant-reported Quality of Life Surveys

Also known as: QoL Surveys

Participants in remission, No ADT (Prostate cancer Control (PC) Cohort)); Participants with prostate cancer, ADT (ADT Cohort); Partners of Participants

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Participants with prostate cancer and partners of participants. The analysis population will consist of participants who complete baseline plasma Aβ42/40 and apolipoprotein E4 (APOE4) collection and the cognitive assessments at baseline and at least 3 months.

You may qualify if:

• Patient Participants-
• Age 18 years or greater.
• Fluent in reading, listening to, and writing English.
• Current or prior diagnosis of prostate adenocarcinoma based on a pathology report or as documented in a medical oncology, urology, or radiation oncology note.
• Access and ability to use a computer or mobile device with Internet connectivity to complete study procedures.
• Telephone Montreal Cognitive Assessment (T-MoCA) of 16 or greater.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (documented within past 3 months, otherwise patient-reported).
• Study partner participants-
• Age 18 years or greater
• Fluent in reading, listening to, and writing English
• Identified by patient participant as a person who knows patient participant well, like a friend, family member or spouse.
• Access and ability to use a computer or mobile device with internet connectivity to complete study procedures.
• Only the ADT cohort-
• Anticipated to start ADT, which includes one of the following two treatments
• Gonadotropin-releasing hormone (GnRH) agonist (e.g., leuprolide, goserelin, and others).

You may not qualify if:

• Patient Participants-
• Small cell prostate carcinoma (pure or mixed).
• Receipt of ADT (GnRH agonist, GnRH antagonist, 1st-generation anti-androgen, or novel androgen signaling inhibitor) within 6 months before screening. ADT \>6 months prior to screening is allowed provided testosterone has recovered to 100 ng/ml or greater.
• Concurrent or anticipated (at any point during first 12 months of ADT) non-hormonal, antineoplastic systemic therapy, such as chemotherapy.
• Testosterone \<100 ng/ml.
• Prior or concurrent brain metastases (no prior or screening imaging is required).
• Major neurocognitive or psychiatric disorders, such as dementia or schizophrenia.
• Prior or concurrent malignancy other than prostate cancer whose natural history or treatment has the potential to interfere with study assessments.
• Study partner participants-
• None.
• Only the ADT cohort-
• None.
• Only the PC cohort-
• Any prior, concurrent, or anticipated use of any hormonal systemic therapy, including GnRH agonist, GnRH antagonist, 1st-generation anti-androgen, or novel androgen signaling inhibitor.
• Any known or prior history of M1 prostate cancer (no screening imaging required).

Sponsors & Collaborators

• University of California, San Francisco: lead

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94143, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

Blood specimens will be collected

MeSH Terms

Conditions

Prostatic Neoplasms; Cognitive Dysfunction

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Study Officials

• Daniel Kwon, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 7, 2023
• First Posted: April 20, 2023
• Study Start: May 22, 2023
• Primary Completion: February 28, 2026
• Study Completion: February 28, 2026
• Last Updated: February 24, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)