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

Official title

A Phase II Randomized Study of Interventions for Metabolic Protection Against Cardiometabolic Toxicity During Androgen Deprivation Therapy (IMPACT-ADT)

Overview

This phase II trial compares the effect of time-restricted eating (TRE) and glucagon-like peptide-1 (GLP1) receptor agonists (RA), semaglutide and tirzepatide, to an American Heart Association (AHA) heart healthy diet (HHD) intervention on heart and blood vessel health (cardiovascular system) and how the body processes food for energy (metabolic system) in prostate cancer patients undergoing androgen deprivation therapy (ADT). Prostate cancer patients who are receiving hormonal therapy (ADT) are at an increased risk of cardiovascular disease. This is thought to be due to treatment-related metabolic changes which may result in increased weight, body fat, insulin resistance and an increased risk of heart attack, stroke or other heart and blood vessel problems. TRE (also known as intermittent fasting) is an eating plan that alternates between fasting and non-fasting periods. This approach limits calorie intake to a specific window of time each day. GLP1-RAs, semaglutide and tirzepatide are in a class of medications called incretin mimetics. They work by helping the pancreas to release the right amount of insulin when blood sugar levels are high. Insulin helps move sugar from the blood into other body tissues where it is used for energy. They also slow the movement of food through the stomach and may decrease appetite and cause weight loss. The AHA HHD guidelines may be an effective method to help people learn about following a heart healthy eating plan. This may lower their risk of cardiovascular disease. Metabolic interventions, TRE and GLP1-RA, may be more effective than an AHA HHD intervention alone in improving cardiovascular and metabolic health in prostate cancer patients undergoing ADT.

Detailed description

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.

Interventions

• Drug Antiandrogen Therapy
  Given ADT
• Behavioral Behavioral Intervention
  Receive fasting reminders via Oncpatient Companion Mobile Application
• Procedure Biospecimen Collection
  Undergo blood sample collection
• Procedure Cardiac Computerized Tomographic Angiography
  Undergo a coronary computerized tomography angiography
• Procedure Computed Tomography
  Undergo CT
• Other Electronic Health Record Review
  Ancillary studies
• Other Internet-Based Intervention
  Complete survey and food diary collection via Oncpatient Companion Mobile Application
• Behavioral Lifestyle Counseling
  Receive diet and lifestyle counseling
• Other Medical Device Usage and Evaluation
  Wear an activity tracker
• Other Nutritional Intervention
  Receive AHA HHD guidelines

Primary outcome measures

• Changes in the 10-year risk of cardiovascular disease [Time frame: At completion of 6 months of androgen deprivation therapy (ADT) and at 12 months follow up after completion of ADT]
• Changes in the 10-year risk of cardiovascular disease [Time frame: At completion of 6 months of ADT and at 12 months follow up after completion of ADT]

Secondary outcome measures (10)

• Changes in the 10-year risk of cardiovascular disease [Time frame: At completion of 6 months of ADT and at 12 months follow up after completion of ADT]
• Incidence of de novo metabolic syndrome [Time frame: At completion of 6 months of ADT and at 12 months follow up after completion of ADT]
• Changes in visceral adiposity [Time frame: At completion of 6 months of ADT and at 12 months follow up after completion of ADT]
• Changes in muscle mass [Time frame: At completion of 6 months of ADT and at 12 months follow up after completion of ADT]
• Evidence of endothelial dysfunction [Time frame: At completion of 6 months of ADT and at 12 months follow up after completion of ADT]
• Percent of patients who successfully complete interventions [Time frame: Up to 12 months after completion of ADT]
• Quality of life - International Prognostic Scoring System [Time frame: At baseline and up to 12 months after completion of ADT]
• Quality of life - Sexual Health Inventory for Men [Time frame: At baseline and up to 12 months after completion of ADT]
• Quality of life - Merrick rectal function [Time frame: At baseline and up to 12 months after completion of ADT]
• Quality of life - Patient Reported Outcomes Measurement Information System 29 [Time frame: At baseline and up to 12 months after completion of ADT]

Eligibility criteria

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)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Prevention

Study locations

United States · 1 center

• City of Hope Medical Center — Duarte

Identifiers

NCT: NCT07202247 · 25332 · NCI-2025-06197 · 25332 · P30CA033572

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗