Predicting Cognitive Decline From Androgen Deprivation Therapy

Prostate Cancer Clinical Trial

— ABC  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05820932
• Other study ID #: 22806
• Secondary ID: NCI-2023-02192
• Status: Recruiting
• Start date: May 22, 2023
• Est. completion date: May 31, 2026

Study information

• Verified date: August 2023
• Source: University of California, San Francisco
• Contact: UCSF Genitourinary Medical Oncology Recruitment
• Phone: 877-827-3222
• Email: GUTrials[@]ucsf.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 240
• Est. completion date: May 31, 2026
• Est. primary completion date: May 31, 2026
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Cognitive Dysfunction
• Prostate Cancer
• Prostatic Neoplasms

Intervention

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

Locations

Country	Name	City	State
United States	University of California, San Francisco	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
University of California, San Francisco

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	Change in mean plasma Aß42/40 ratio	Change in mean plasma Aß42/40 ratio for the ADT cohort at 12 months will be compared to that of the PC control cohort	Up to 12 months
Secondary	Mean cognition score	The Z-scores of each cognitive test will be calculated as a repeated measure.	Up to 12 months
Secondary	Mean study partner-reported cognition score	The Z-scores of each cognitive test will be calculated as a repeated measure.	Up to 12 months