Metabolic Interventions (Time-Restricted Eating, GLP1 Receptor Agonist, and Heart Healthy Diet) to Improve Cardiometabolic Health in Prostate Cancer Patients During Androgen Deprivation Therapy, IMPACT-ADT Trial

PRIMARY OBJECTIVE:

I. Evaluate whether metabolic interventions, including TRE and GLP1-RA treatment, improve the cardiometabolic health of prostate cancer (PCa) patients undergoing ADT.

SECONDARY OBJECTIVES:

I. Characterize the metabolic and inflammatory profiles for patients at high risk of ADT-associated cardiometabolic disease during ADT.

II. Evaluate tolerability and feasibility of concurrently using GLP1-RA or performing TRE during short-term ADT.

III. Examine if metabolic interventions, including TRE and GLP1 RA treatment, are associated with improved patient quality of life.

EXPLORATORY OBJECTIVES:

I. Define the impact of metabolic interventions, including TRE and GLP1 RA treatment, on ADT-induced metabolome-inflammasome dysfunction.

II. Evaluate the impact of metabolic interventions, including TRE and GLP1 RA treatment, on clonal dynamics following ADT.

III. Evaluate how metabolic interventions, including TRE and GLP1 RA treatment, impact coronary plaque characteristics in PCa patients undergoing ADT.

OUTLINE: Patients are randomized to 1 of 3 arms.

ARM 1 (TRE): Patients receive radiation therapy (RT) and ADT per standard of care (SOC), as well as participate in an overnight fast over 16 hours on at least 5 days weekly for 6 months. Patients also receive TRE reminders, dietary education, and complete survey and food diary collection via the Oncpatient Companion Mobile Application (app). In addition, patients receive diet/lifestyle counseling as per AHA HHD guidelines and AHA Life Essential 8 recommendations with personalized caloric intake for 6 months. Patients may may optionally wear an activity tracker throughout the trial.

ARM 2 (GLP1-RA): Patients receive RT and ADT per SOC for 6 months. Patients receive a referral to an endocrinologist and receive semaglutide or tirzepatide subcutaneously (SC) once weekly (QW) for 6 months in the absence of disease progression or unacceptable toxicity. Patients also receive dietary education and complete survey and food diary collection via the Oncpatient Companion Mobile app. In addition, patients receive diet/lifestyle counseling as per AHA HHD guidelines and AHA Life Essential 8 recommendations with personalized caloric intake for 6 months. Patients may may optionally wear an activity tracker throughout the trial.

ARM 3 (AHA HHD): Patients receive RT and ADT per SOC for 6 months. Patients receive diet/lifestyle counseling as per AHA HHD guidelines and AHA Life Essential 8 recommendations with personalized caloric intake for 6 months. Patients also receive dietary education and complete survey and food diary collection via the Oncpatient Companion Mobile app. Patients may may optionally wear an activity tracker throughout the trial.

Additionally, patients undergo computed tomography (CT), blood sample collection throughout the study, and may optionally undergo a coronary computerized tomography angiography throughout the study.

After completion of study intervention, patients are followed up at 30 days and at 12 months.

• Antiandrogen Therapy (Drug), also known as ADT, Androgen Deprivation Therapy, Androgen Deprivation Therapy (ADT), Anti-androgen Therapy, Anti-androgen Treatment, Antiandrogen Treatment, Hormone Deprivation Therapy, Hormone-Deprivation Therapy: Given ADT
• Behavioral Intervention (Behavioral), also known as Behavior Conditioning Therapy, Behavior Modification, Behavior or Life Style Modifications, Behavior Therapy, Behavioral, Behavioral Interventions, Behavioral Modification, Behavioral Therapy, Behavioral Treatment, Behavioral Treatments: Receive fasting reminders via Oncpatient Companion Mobile Application
• Biospecimen Collection (Procedure), also known as Biological Sample Collection, Biospecimen Collected, Specimen Collection: Undergo blood sample collection
• Cardiac Computerized Tomographic Angiography (Procedure): Undergo a coronary computerized tomography angiography
• Computed Tomography (Procedure), also known as CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography: Undergo CT
• Electronic Health Record Review (Other): Ancillary studies
• Internet-Based Intervention (Other): Complete survey and food diary collection via Oncpatient Companion Mobile Application
• Lifestyle Counseling (Behavioral): Receive diet and lifestyle counseling
• Medical Device Usage and Evaluation (Other): Wear an activity tracker
• Nutritional Intervention (Other): Receive AHA HHD guidelines
• Nutritional Intervention (Other): Receive AHA Life Essential 8 recommendations with personalized caloric intake
• Questionnaire Administration (Other): Ancillary studies
• Radiation Therapy (Radiation), also known as Cancer Radiotherapy, Energy Type, ENERGY_TYPE, Irradiate, Irradiated, Irradiation, Radiation, Radiation Therapy, NOS, Radiotherapeutics, Radiotherapy, RT, Therapy, Radiation: Undergo RT
• Referral (Other), also known as Referred: Receive a referral to an endocrinologist
• Semaglutide (Drug), also known as Ozempic, Rybelsus, Wegovy: Given SC
• Short-Term Fasting (Other), also known as Intermittent Fasting, Short-term Intermittent Fasting: Participate in an overnight fast
• Tirzepatide (Drug): Given SC

Primary outcomes

• Changes in the 10-year risk of cardiovascular disease [At completion of 6 months of androgen deprivation therapy (ADT) and at 12 months follow up after completion of ADT]: The changes in the American Heart Association Predicting Risk of cardiovascular disease (CVD) EVENTs (AHA PREVENT) risk score will be compared between glucagon-like peptide-1 receptor agonist (GLP1-RA) versus (vs.) AHA heart healthy diet (AHA HHD) interventions using a 2-group t-test with a 0.050 one-sided significance level.
• Changes in the 10-year risk of cardiovascular disease [At completion of 6 months of ADT and at 12 months follow up after completion of ADT]: The changes in the AHA PREVENT risk score will be compared between time-restricted eating (TRE) vs. AHA HHD interventions using a 2-group t-test with a 0.050 one-sided significance level.

Secondary outcomes

• Changes in the 10-year risk of cardiovascular disease [At completion of 6 months of ADT and at 12 months follow up after completion of ADT]: The changes in the AHA PREVENT risk score will be compared between GLP1-RA vs. TRE interventions.
• Incidence of de novo metabolic syndrome [At completion of 6 months of ADT and at 12 months follow up after completion of ADT]
• Changes in visceral adiposity [At completion of 6 months of ADT and at 12 months follow up after completion of ADT]: Will be measured using computed tomography and bioelectrical impedance analysis.
• Changes in muscle mass [At completion of 6 months of ADT and at 12 months follow up after completion of ADT]: Will be measured using computed tomography and bioelectrical impedance analysis.
• Evidence of endothelial dysfunction [At completion of 6 months of ADT and at 12 months follow up after completion of ADT]: Will be measured by flow mediated dilation of the brachial artery.
• Percent of patients who successfully complete interventions [Up to 12 months after completion of ADT]: Tolerability and feasibility will be defined as at least 70% of enrolled patients successfully completing the interventions for a minimum of 70% of the study duration.
• Quality of life - International Prognostic Scoring System [At baseline and up to 12 months after completion of ADT]: Will be measured using the International Prognostic Scoring System.
• Quality of life - Sexual Health Inventory for Men [At baseline and up to 12 months after completion of ADT]: Will be measured using the Sexual Health Inventory for Men.
• Quality of life - Merrick rectal function [At baseline and up to 12 months after completion of ADT]: Will be measured using the Merrick rectal function.
• Quality of life - Patient Reported Outcomes Measurement Information System 29 [At baseline and up to 12 months after completion of ADT]: Will be measured using the Patient Reported Outcomes Measurement Information System 29.

Sex: Male, ages: 30 Years to 79 Years

Inclusion Criteria:

* Documented informed consent of the participant
* English, Spanish or Mandarin-speaking
* Agreement to allow the use of archival tissue from diagnostic tumor biopsies

  * If unavailable, exceptions may be granted with study principal investigator (PI) approval
* Male
* Aged: 30-79
* Eastern Cooperative Oncology Group (ECOG) 0-2
* High burden of cardiovascular comorbidities who would be eligible for insurance coverage for GLP1-RA therapy defined as:

  * Body mass index (BMI) of ≥ 30 kg/m\^2 or
  * BMI ≥ 27 kg/m\^2 in the presence of at least one weight-related comorbid condition (e.g. hypertension, type 2 diabetes mellitus, dyslipidemia)
* Prostate cancer defined as one of the following:

  * National Comprehensive Cancer Network (NCCN) intermediate risk prostate cancer receiving definitive radiation with a plan to undergo ADT for 6 months
  * Biochemical persistent or recurrent prostate cancer status post prostatectomy receiving salvage radiation with a plan to undergo ADT for 6 months

Exclusion Criteria:

* Currently engaging in strict macronutrient/time limited diet, including ketogenic, low-carb, paleo, or warrior diet
* Currently under GLP1-RA therapy
* Poorly controlled diabetes
* Unable to undergo time-restricted diet
* Contraindications for GLP1-RA therapy: including hypersensitivity to the drug, personal history of pancreatitis, personal or family history of medullary thyroid cancer or multiple endocrine neoplasia syndrome type 2, end-stage renal disease
* Other active disease deemed not eligible to participant in the study according to treating physician
* Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

• Rose Li, Principal investigator, City of Hope Medical Center

NIH grants: P30CA033572