Metabolic Impact of Prospective Controlled Mediterranean Type Diets on Prostate Cancer

Elucidating the Metabolic Impact of Isocaloric, Controlled, Mediterranean-Type Diets in Treatment-Naïve Men With Prostate Cancer on Active Surveillance (DINE Study)

The purpose of this study is to examine the impact of Mediterranean-type diets on the metabolism of men with localized prostate cancer.

The optimal diet for men with a suspected diagnosis of Prostate Cancer (PCa) is currently unknown. More specifically, the suggested benefits of low carbohydrate and low fat diets in PCa are not determined.

Study Overview

• Status: Not yet recruiting
• Conditions: Prostate Cancer
• Intervention / Treatment: Other: Lower-Carbohydrate Med-t-Diet; Other: Low-Fat Med-t-Diet

Detailed Description

Primary Objective

-Evaluate the impact of Mediterranean diets (Med-t-Diets) on non-malignant prostate tissue metabolism

Secondary Objectives

• Evaluate the impact of Med-t-Diets on host metabolism
• Evaluate the impact of Med-t-Diets on systemic biomarkers after consuming Med-t-Diets
• Evaluate the impact of Med-t-Diets on the microbiome and dietary behavior and compliance after consuming Med-t-Diets

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Dianna Sendrey, RN, BSN; Phone Number: (216) 444-0486; Email: sendred2@ccf.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Males ≥18 years old
• High suspicion of prostate cancer (PCa) per urologist's clinical evaluation
• BMI >18.5
• No prior PCa diagnosis or hormonal therapy (-ies)
• Ability to read, write, speak, and understand English
• Ability to provide informed consent
• Candidate for and elects active surveillance (AS) if diagnostic biopsy is positive
• Willingness to consume provided dietary interventions
• Adequate organ and marrow function: White blood cell count (WBC) ≥2,500/mcL, Absolute neutrophil count (ANC) ≥1,500/mcL, Platelets ≥100,000/mcL, Hemoglobin ≥9 g/dL (transfusions permitted), Total bilirubin ≤1.5 x the institutional upper limit of normal (ULN) (for subjects with Gilbert's disease ≤3.0 mg/dL), Aspartate aminotransferase (AST)/Alanine aminotransferase (ALT) ≤2.5 x institutional ULN, Creatinine clearance ≥51 ml/min as defined by Cockcroft-Gault equation

Exclusion Criteria:

• Currently consuming a Mediterranean, lower carbohydrate, ketogenic, vegan, vegetarian, high fiber diet (14g fiber > per 1,000 Calories) and/or any supplements (including herbal), vitamins, minerals, that would interfere with diets being tested in the study as determined by dietitian and/or investigators.
• Previous intolerability to fiber-rich diets
• Colitis, Irritable Bowel Syndrome, or other gastrointestinal condition per clinician discretion
• Unwilling to undergo transperineal PCa biopsies
• Food allergies or other major dietary restrictions
• Receiving active medical treatment for Type I or Type II diabetes mellitus
• Prior antibiotic usage (i.e. within last 30 days) at time of consent
• Recent weight loss (both intentional and unintentional) as defined by 5%+ body weight in the last 30 days
• Undergone any type of weight loss surgery
• Any medical contraindications as determined by investigators
• High risk as defined by PSA≥20 and/or PI-RADS 5 lesion as per clinician evaluation
• History of diabetic ketoacidosis
• Gout
• Patients that are immunosuppressed (transplant history, on immunosuppression, etc.) as per clinician discretion
• Recent (within last 30 days) device implant/joint requiring antibiotics as per clinician determination
• Prior history of prostate biopsy infection
• Uncontrolled hypertension as defined by blood pressure greater than 140/80 (with or without medication)
• Gallbladder removed or plan to remove per clinician evaluation
• Other malignancies actively receiving systemic treatment as per clinician evaluation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mediterranean-type Diet(s)-Arm 1; Diet randomization occurs two weeks prior to the Standard of Care (SOC) diagnostic biopsy. If patient is randomized to Arm 1, they will receive Low Fat (LF) Mediterranean Diet first. The results of the diagnostic biopsy determines how the patient will proceed on the trial. If there is a confirmed Prostate Cancer (PCa) diagnosis AND is a candidate for Active Surveillance (AS) per SOC, then patient will undergo a washout period and cross-over to the Lower Carbohydrate (LC) Mediterranean Diet two weeks prior to the SOC confirmatory biopsy. A long-term follow-up (LTFU) visit will occur 3 months after the second dietary intervention has concluded. If patient does not have PCa or is not placed on AS, then they will only have the first dietary intervention and a LTFU visit 3 months after	Other: Lower-Carbohydrate Med-t-Diet; Diet will focus on including: Lean protein sources; High-quality fat; High-quality carbohydrate sources that are rich in fiber; Nuts and seeds Diet will focus on limiting: Refined sugars; High glycemic carbohydrates; Seed oils that may cause inflammation Diet Composition: 45% fats, 35% carbs, 20% protein; Other: Low-Fat Med-t-Diet; Diet will focus on including: Lean protein sources; High-quality fat; High-quality carbohydrate sources that are rich in fiber; Nuts and seeds Diet will focus on limiting: Refined sugars; High glycemic carbohydrates; Seed oils that may cause inflammation Diet Composition: 70% carbs, 20% protein, 10% fat
Experimental: Mediterranean-type Diet(s)-Arm 2; Diet randomization occurs two weeks prior to the Standard of Care (SOC) diagnostic biopsy. If patient is randomized to Arm 2, they will receive Lower Carbohydrate (LC) Mediterranean Diet first. The results of the diagnostic biopsy determines how the patient will proceed on the trial. If there is a confirmed Prostate Cancer (PCa) diagnosis AND is a candidate for Active Surveillance (AS) per SOC, then patient will undergo a washout period and cross-over to the Low Fat (LF) Mediterranean Diet two weeks prior to the SOC confirmatory biopsy. A long-term follow-up (LTFU) visit will occur 3 months after the second dietary intervention has concluded. If patient does not have PCa or is not placed on AS, then they will only have the first dietary intervention and a LTFU visit 3 months after.	Other: Lower-Carbohydrate Med-t-Diet; Diet will focus on including: Lean protein sources; High-quality fat; High-quality carbohydrate sources that are rich in fiber; Nuts and seeds Diet will focus on limiting: Refined sugars; High glycemic carbohydrates; Seed oils that may cause inflammation Diet Composition: 45% fats, 35% carbs, 20% protein; Other: Low-Fat Med-t-Diet; Diet will focus on including: Lean protein sources; High-quality fat; High-quality carbohydrate sources that are rich in fiber; Nuts and seeds Diet will focus on limiting: Refined sugars; High glycemic carbohydrates; Seed oils that may cause inflammation Diet Composition: 70% carbs, 20% protein, 10% fat

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate the impact of Med-t-Diets on non-malignant prostate tissue metabolism	Change in non-malignant prostate tissue metabolomics using mass spectrometry to assess differences in ions/metabolites and corresponding metabolic pathways after different dietary interventions expressed as a fold-change. As an exploratory study, metabolomics will be untargeted and as such is not run with a standard curve and does not have a unit of measure.	Change from diagnostic biopsy (Week 2) at confirmatory biopsy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in blood metabolomics	Change in blood metabolomics using mass spectrometry to assess differences in ions/metabolites and corresponding metabolic pathways after different dietary interventions expressed as a fold-change. As an exploratory study, metabolomics will be untargeted and as such is not run with a standard curve and does not have a unit of measure	Change from baseline at two weeks on diet
Changes in energy substrate(s)	Change measured by respiratory exchange ratio (VCO2/VO2) difference between baseline and at two weeks on diet	Change from baseline at two weeks on diet
Changes in blood glucose (mg/dL)	Change as measured by the difference between blood glucose levels at baseline and at week two on diet	Change from baseline at two weeks on diet
Changes in ketone levels (mM or mcg/mL)	Change measured by the difference between ketone levels between baseline and at two weeks on diet	Change from baseline at two weeks on diet
Changes in hemoglobin A1C (HbA1C) (%)	Change measured by the difference between A1C levels at baseline and at 2 weeks on diet	Change from baseline at two weeks on diet
Changes in C-reactive protein (CRP) (mg/L)	Change measured by the difference between CRP levels at baseline and at 2 weeks on diet	Change from baseline at two weeks on diet
Changes in lipid particle size (nm)	Change measured by the difference in lipid particle size at baseline and at 2 weeks on diet using Nuclear Magnetic Resonance (NMR).	Change from baseline at two weeks on diet
Changes in lipid particle number (nmol/L and/or μmol/L)	Change measured by the difference in lipid particle number at baseline and at 2 weeks on diet using Nuclear Magnetic Resonance (NMR)	Change from baseline at two weeks on diet
Changes in insulin sensitivity [(Homeostatic Model Assessment of Insulin Resistance (HOMA-IR score)]	Change as measured by the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) score using fasting insulin and glucose from longitudinal blood specimens at baseline and at two weeks on diet. The HOMA-IR test tests how resistant a participant is to insulin. A score of less than 1 indicates that a participant is insulin-sensitive, a score greater than 1.9 indicates some insulin resistance, and a score greater than 2.9 indicates significant insulin resistance.	Change from baseline at two weeks on diet
Prostate health changes	As measured by changes in the Prostate Health Index	Change from baseline at two weeks on diet
Safety and tolerability of the diets	Safety and tolerability measured by the number of adverse events and by the gastric tolerance questionnaire	Through study completion, an average of 7.5 month
Changes in alpha and beta diversity of the gut microbiome	Changes measured by Shannon or Simpson diversity index (alpha diversity) and pairwise Bray-Curtis metric values (beta diversity)	Change from baseline at two weeks on diet
Changes in dietary behavior	Behavioral changes measured by validated 24 hour dietary recalls collected by trained dietetics personnel on 2 week days and 1 weekend to capture specific dietary information	Through study completion, an average of 7.5 months
Diet compliance	Compliance measured by >90% of provided calories consumed	throughout controlled feeding period(s), two weeks per diet

Collaborators and Investigators

• Sponsor: Case Comprehensive Cancer Center
• Investigators: Principal Investigator: Christopher Weight, MD, Center Director, Cleveland Clinic Urologic Oncology

Publications and helpful links

General Publications

• Ornish D, Weidner G, Fair WR, Marlin R, Pettengill EB, Raisin CJ, Dunn-Emke S, Crutchfield L, Jacobs FN, Barnard RJ, Aronson WJ, McCormac P, McKnight DJ, Fein JD, Dnistrian AM, Weinstein J, Ngo TH, Mendell NR, Carroll PR. Intensive lifestyle changes may affect the progression of prostate cancer. J Urol. 2005 Sep;174(3):1065-9; discussion 1069-70. doi: 10.1097/01.ju.0000169487.49018.73.
• Freedland SJ, Howard L, Allen J, Smith J, Stout J, Aronson W, Inman BA, Armstrong AJ, George D, Westman E, Lin PH. A lifestyle intervention of weight loss via a low-carbohydrate diet plus walking to reduce metabolic disturbances caused by androgen deprivation therapy among prostate cancer patients: carbohydrate and prostate study 1 (CAPS1) randomized controlled trial. Prostate Cancer Prostatic Dis. 2019 Sep;22(3):428-437. doi: 10.1038/s41391-019-0126-5. Epub 2019 Jan 21.

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2024
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: September 23, 2022
• First Submitted That Met QC Criteria: October 19, 2022
• First Posted (Actual): October 21, 2022

Study Record Updates

• Last Update Posted (Actual): February 15, 2024
• Last Update Submitted That Met QC Criteria: February 14, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Mediterranean-type Diets
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Appetite Depressants; Anti-Obesity Agents; Central Nervous System Stimulants; Sympathomimetics; Phentermine
• Other Study ID Numbers: CASE4822

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No