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

Clinicaltrials.gov ID: NCT07202247

Status RECRUITING

Phase PHASE2

Age 30 - 79 Years

Enrollments 60

Conditions

Prostate Carcinoma, Recurrent Prostate Carcinoma

Drugs

Antiandrogen Therapy, Semaglutide, Tirzepatide

Summary

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.

Locations

1 location Found with status Recruiting

Status

RECRUITING

Contact Person

Rose Li
508-864-7639
[email protected]

Principal Investigator

Rose Li

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)

Study Plan

Arm 1 (TRE)

EXPERIMENTAL

Patients receive RT and ADT per 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 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. Additionally, patients undergo CT, blood sample collection throughout the study and may optionally undergo a coronary computerized tomography angiography throughout the study.

DRUG:
Antiandrogen Therapy
Description:
Given ADT
BEHAVIORAL:
Behavioral Intervention
Description:
Receive fasting reminders via Oncpatient Companion Mobile Application
PROCEDURE:
Biospecimen Collection
Description:
Undergo blood sample collection
PROCEDURE:
Cardiac Computerized Tomographic Angiography
Description:
Undergo a coronary computerized tomography angiography
PROCEDURE:
Computed Tomography
Description:
Undergo CT
OTHER:
Electronic Health Record Review
Description:
Ancillary studies
OTHER:
Internet-Based Intervention
Description:
Complete survey and food diary collection via Oncpatient Companion Mobile Application
BEHAVIORAL:
Lifestyle Counseling
Description:
Receive diet and lifestyle counseling
OTHER:
Medical Device Usage and Evaluation
Description:
Wear an activity tracker
OTHER:
Nutritional Intervention
Description:
Receive AHA HHD guidelines
OTHER:
Nutritional Intervention
Description:
Receive AHA Life Essential 8 recommendations with personalized caloric intake
OTHER:
Questionnaire Administration
Description:
Ancillary studies
RADIATION:
Radiation Therapy
Description:
Undergo RT
OTHER:
Short-Term Fasting
Description:
Participate in an overnight fast

Arm 2 (semaglutide, tirzepatide)

EXPERIMENTAL

Patients receive RT and ADT per SOC for 6 months. Patients receive a referral to an endocrinologist and receive semaglutide or tirzepatide SC 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. Additionally, patients undergo CT, blood sample collection throughout the study and may optionally undergo a coronary computerized tomography angiography throughout the study.

DRUG:
Antiandrogen Therapy
Description:
Given ADT
PROCEDURE:
Biospecimen Collection
Description:
Undergo blood sample collection
PROCEDURE:
Cardiac Computerized Tomographic Angiography
Description:
Undergo a coronary computerized tomography angiography
PROCEDURE:
Computed Tomography
Description:
Undergo CT
OTHER:
Electronic Health Record Review
Description:
Ancillary studies
OTHER:
Internet-Based Intervention
Description:
Complete survey and food diary collection via Oncpatient Companion Mobile Application
BEHAVIORAL:
Lifestyle Counseling
Description:
Receive diet and lifestyle counseling
OTHER:
Medical Device Usage and Evaluation
Description:
Wear an activity tracker
OTHER:
Nutritional Intervention
Description:
Receive AHA HHD guidelines
OTHER:
Nutritional Intervention
Description:
Receive AHA Life Essential 8 recommendations with personalized caloric intake
OTHER:
Questionnaire Administration
Description:
Ancillary studies
RADIATION:
Radiation Therapy
Description:
Undergo RT
OTHER:
Referral
Description:
Receive a referral to an endocrinologist
DRUG:
Semaglutide
Description:
Given SC
DRUG:
Tirzepatide
Description:
Given SC

Arm 3 (AHA HDD)

ACTIVE_COMPARATOR

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 CT, blood sample collection throughout the study and may optionally undergo a coronary computerized tomography angiography throughout the study.

DRUG:
Antiandrogen Therapy
Description:
Given ADT
PROCEDURE:
Biospecimen Collection
Description:
Undergo blood sample collection
PROCEDURE:
Cardiac Computerized Tomographic Angiography
Description:
Undergo a coronary computerized tomography angiography
PROCEDURE:
Computed Tomography
Description:
Undergo CT
OTHER:
Electronic Health Record Review
Description:
Ancillary studies
OTHER:
Internet-Based Intervention
Description:
Complete survey and food diary collection via Oncpatient Companion Mobile Application
BEHAVIORAL:
Lifestyle Counseling
Description:
Receive diet and lifestyle counseling
OTHER:
Medical Device Usage and Evaluation
Description:
Wear an activity tracker
OTHER:
Nutritional Intervention
Description:
Receive AHA HHD guidelines
OTHER:
Nutritional Intervention
Description:
Receive AHA Life Essential 8 recommendations with personalized caloric intake
OTHER:
Questionnaire Administration
Description:
Ancillary studies
RADIATION:
Radiation Therapy
Description:
Undergo RT

Outcome Measures

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