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.

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)