Akkermansia Muciniphilia and Metabolic Side Effects of ADT

Sponsor

Western University (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05802121

Collaborator

(none)

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

The overriding objectives of this study are:

Primary outcomes:
To confirm that administration of oral acetate increases the proportion of A. muciniphilia in the stool samples of patients with metastatic, castration-sensitive prostate cancer compared to placebo.
To confirm tolerability and assess for side effects of delayed oral acetate supplementation.
Secondary outcomes:
To determine if increased counts of A. muciniphilia correlate with improved metabolic parameters and improved bone health.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer Metabolic Syndrome Obesity Cardiovascular Morbidity Bone Diseases Hyperlipidemias Diabetes	Drug: Apple Cider Vinegar Drug: Placebo	Early Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

This will be a single-institution, randomized placebo-controlled trial involving men ≥18 years of age with metastatic castration-sensitive prostate cancer. This study will require histologic confirmation of prostate adenocarcinoma and radiographic evidence of metastatic disease on conventional imaging (CT or BS). Patients will be randomized 1:1 to receive acetate supplementation or placebo. Our institution sees approximately 200 new metastatic prostate cancer patients each year, therefore, the investigators do not anticipate encountering difficulties with recruitment into this study over a period of 2 years.This will be a single-institution, randomized placebo-controlled trial involving men ≥18 years of age with metastatic castration-sensitive prostate cancer. This study will require histologic confirmation of prostate adenocarcinoma and radiographic evidence of metastatic disease on conventional imaging (CT or BS). Patients will be randomized 1:1 to receive acetate supplementation or placebo. Our institution sees approximately 200 new metastatic prostate cancer patients each year, therefore, the investigators do not anticipate encountering difficulties with recruitment into this study over a period of 2 years.

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

Both participants and investigators will be blinded to the intervention, either the apple cider vinegar pills vs. acetate.

Primary Purpose:

Prevention

Official Title:

The Role of Akkermansia Muciniphilia in Combating the Metabolic Effects of Androgen Deprivation Therapy in Men With Metastatic Prostate Cancer

Anticipated Study Start Date :

Jun 1, 2023

Anticipated Primary Completion Date :

Jun 1, 2025

Anticipated Study Completion Date :

Jun 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Apple Cider Vinegar Webbers Natural apple cider vinegar pills (NPN: 80021269), enteric coated. Each patient will be instructed to take 6 enteric slow-release acetate capsules (equivalent of 500 mg/ capsule containing 25 mg acetate x 6 capsules) per day for 3 months.	Drug: Apple Cider Vinegar Each patient will be instructed to take 6 enteric slow-release acetate capsules (equivalent of 500 mg/ capsule containing 25 mg acetate x 6 capsules) per day for 3 months https://www.webbernaturals.com/en-ca/apple-cider-vinegar-500-mg-capsules/
Placebo Comparator: Placebo Placebo pills will be provided by our hospital pharmacy, and patients will be given the same instructions as in the treatment arm.	Drug: Placebo Each patient will be instructed to take 6 placebo capsules per day for 3 months

Arm

Intervention/Treatment

Experimental: Apple Cider Vinegar

Webbers Natural apple cider vinegar pills (NPN: 80021269), enteric coated. Each patient will be instructed to take 6 enteric slow-release acetate capsules (equivalent of 500 mg/ capsule containing 25 mg acetate x 6 capsules) per day for 3 months.

Drug: Apple Cider Vinegar

Each patient will be instructed to take 6 enteric slow-release acetate capsules (equivalent of 500 mg/ capsule containing 25 mg acetate x 6 capsules) per day for 3 months https://www.webbernaturals.com/en-ca/apple-cider-vinegar-500-mg-capsules/

Placebo Comparator: Placebo

Placebo pills will be provided by our hospital pharmacy, and patients will be given the same instructions as in the treatment arm.

Drug: Placebo

Each patient will be instructed to take 6 placebo capsules per day for 3 months

Outcome Measures

Primary Outcome Measures

Fecal Akkermansia muciniphilia counts [1 week]
Counts of Akkermansia muciniphilia in participant stool samples at 1 week following the intervention will be compared to baseline counts.
Fecal Akkermansia muciniphilia counts [1 month]
Counts of Akkermansia muciniphilia in participant stool samples at 1 month following the intervention will be compared to baseline counts.
Fecal Akkermansia muciniphilia counts [3 month]
Counts of Akkermansia muciniphilia in participant stool samples at 3 months following the intervention will be compared to baseline counts.
Fecal Akkermansia muciniphilia counts [4 month]
Counts of Akkermansia muciniphilia in participant stool samples at 4 months following the intervention will be compared to baseline counts.
Fecal Akkermansia muciniphilia counts [6 month]
Counts of Akkermansia muciniphilia in participant stool samples at 6 months following the intervention will be compared to baseline counts.
Side effects and tolerability [3 months]
We will record side effects reported by the participants and the rate of Discontinuation of the intervention.

Secondary Outcome Measures

Metabolic parameters: fasting plasma glucose [3 months]
Fasting plasma glucose (mmol/L)
Metabolic parameters: fasting plasma glucose [6 months]
Fasting plasma glucose (mmol/L)
Metabolic parameters: HbA1C [3 months]
HbA1c (%)
Metabolic parameters: HbA1c [6 months]
HbA1c (%)
Metabolic parameters: triglycerides [3 months]
Triglycerides (mmol/L)
Metabolic parameters: triglycerides [6 months]
Triglycerides (mmol/L)
Metabolic parameters: LDL cholesterol [3 months]
LDL cholesterol (mmol/L)
Metabolic parameters: LDL cholesterol [6 months]
LDL cholesterol (mmol/L)
Metabolic parameters: HDL cholesterol [3 months]
HDL cholesterol (mmol/L)
Metabolic parameters: HDL cholesterol [6 months]
HDL cholesterol (mmol/L)
Metabolic parameters: total cholesterol [3 months]
Total cholesterol (mmol/L)
Metabolic parameters: total cholesterol [6 months]
Total cholesterol (mmol/L)
Metabolic parameters: PSA [6 months]
PSA (ng/mL)
Metabolic parameters: PSA [3 months]
PSA (ng/mL)
Metabolic parameters: hemoglobin [3 months]
Hemoglobin (g/L)
Metabolic parameters: hemoglobin [6 months]
Hemoglobin (g/L)
Metabolic parameters: serum creatinine [3 months]
Serum creatinine (µmol/L)
Metabolic parameters: serum calcium [3 months]
Serum calcium (µmol/L)
Metabolic parameters: serum calcium [6 months]
Serum calcium (µmol/L)
Metabolic parameters: alanine transferase [3 months]
Alanine transferase (U/L)
Metabolic parameters: alanine transferase [6 months]
Alanine transferase (U/L)
Metabolic parameters: aspartate aminotransferase [3 months]
Aspartate aminotransferase (U/L)
Metabolic parameters: aspartate aminotransferase [6 months]
Aspartate aminotransferase (U/L)
Metabolic parameters: Insulin resistance index (HOMA IR) [3 months]
Insulin resistance index (HOMA IR)
Metabolic parameters: HOMA IR [6 months]
Insulin resistance index (HOMA IR)
Bone health: dp-ucMGP levels [3 months]
Circulating plasma dp-ucMGP levels (surrogate for vitamin K2 levels) from baseline
Bone health: dp-ucMGP levels [6 months]
Circulating plasma dp-ucMGP levels (surrogate for vitamin K2 levels) from baseline
Bone health: Vitamin K2 [3 months]
Vitamin K2 levels
Bone health: Vitamin K2 [6 months]
Vitamin K2 levels

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

For inclusion in this study, patients must fulfill all of the following criteria:

Men ≥18 years of age with histologically-proven metastatic castration-sensitive prostate adenocarcinoma planned to receive ADT (TNM stage Tany, Nany, M1) (see Appendix I).
Must have baseline conventional imaging with CT of the abdomen, and pelvis and bone scan.

Exclusion Criteria:

Patients fulfilling any of the following criteria are NOT eligible for participation in this study:

Age less than 18
Primary neuroendocrine prostate cancer
Treatment with ADT within the year leading up to enrolment
Unable to provide informed consent or unable to understand or read the English language (unless accompanied by an interpreter)
Inadequate liver function