Predicting Cognitive Decline From Androgen Deprivation Therapy (ABC)

Plasma Amyloid-beta 42/40 to Predict Cognitive Decline From Androgen Deprivation Therapy in Prostate Cancer: a Prospective Observational Study

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.

Study Overview

• Status: Terminated
• Conditions: Prostate Cancer
• Intervention / Treatment: Genetic: Blood-based assay; Diagnostic test: Cognitive assessments; Other: Quality of Life Surveys

Detailed Description

This is a single-site, non-randomized prospective observational study of men with prostate cancer.

PRIMARY OBJECTIVE:

I. To evaluate whether baseline plasma Amyloid-beta 42/40 (Aβ42/40) ratio is associated with cognitive decline in men upon starting ADT.

SECONDARY OBJECTIVE:

I. To evaluate whether ADT is associated with a decline in plasma Aβ42/40 ratio.

II. To evaluate whether intensified ADT (iADT) receipt is associated with greater cognitive decline compared to ADT.

• Study Type: Observational
• Enrollment (Actual): 32

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94143
      • University of California, San Francisco

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• 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.

Description

Inclusion Criteria:

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).
  • GnRH antagonist (i.e., degarelix or relugolix).
• Anticipated to remain on ADT for at least 12 months.
• Concurrent first-generation anti-androgens (e.g., bicalutamide, flutamide, nilutamide) and novel androgen-signaling inhibitors (e.g., abiraterone, enzalutamide, and apalutamide) are allowed.
• Concurrent radiation is allowed.

Only the PC cohort-

• Has completed definitive local therapy (radical prostatectomy or radiation therapy) for localized prostate cancer at least 6 months prior to screening.
• For radical prostatectomy: undetectable prostate-specific antigen (PSA) within 12 months of screening.
• For radiation therapy: last PSA of < 2.0 within 12 months of screening.

Exclusion Criteria:

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).
• Current or prior biochemical recurrence following American Urological Association guidelines for radical prostatectomy or American Society for Therapeutic Radiology and Oncology (ASTRO) guidelines for radiation therapy.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
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; Blood samples will be collected; Diagnostic test: Cognitive assessments; Cognitive assessments will be both participant- and partner-reported; Other: Quality of Life Surveys; Participant-reported Quality of Life Surveys; Other Names: QoL 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; Blood samples will be collected; Diagnostic test: Cognitive assessments; Cognitive assessments will be both participant- and partner-reported; Other: Quality of Life Surveys; Participant-reported Quality of Life Surveys; Other Names: QoL Surveys
Partners of Participants; Study partner participants will also be recruited	Other: Quality of Life Surveys; Participant-reported Quality of Life Surveys; Other Names: QoL Surveys

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in mean plasma Aβ42/40 ratio	Change in mean plasma Aβ42/40 ratio for the ADT cohort at 12 months will be compared to that of the PC control cohort	Up to 12 months
Mean cognition score	The Z-scores of each cognitive test will be calculated as a repeated measure.	Up to 12 months
Mean study partner-reported cognition score	The Z-scores of each cognitive test will be calculated as a repeated measure.	Up to 12 months

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Investigators: Principal Investigator: Daniel Kwon, MD, University of California, San Francisco

Study record dates

Study Major Dates

• Study Start (Actual): May 22, 2023
• Primary Completion (Actual): April 30, 2026
• Study Completion (Actual): April 30, 2026

Study Registration Dates

• First Submitted: April 7, 2023
• First Submitted That Met QC Criteria: April 7, 2023
• First Posted (Actual): April 20, 2023

Study Record Updates

• Last Update Posted (Actual): May 7, 2026
• Last Update Submitted That Met QC Criteria: April 30, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Cognitive decline; Cognitive functioning
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Mental Disorders; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Neurocognitive Disorders; Cognition Disorders; Prostatic Neoplasms; Cognitive Dysfunction
• Other Study ID Numbers: 22806; NCI-2023-02192 (Registry Identifier: NCI Clinical Trials Reporting Program (CTRP))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No