Akkermansia Muciniphilia and Metabolic Side Effects of ADT

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

The overriding objectives of this study are:

1. Primary outcomes:

   1. 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 a standard of care arm.
   2. To confirm tolerability and assess for side effects of oral acetate supplementation.

2. Secondary outcomes:

   1. To determine if increased counts of A. muciniphilia correlate with improved metabolic parameters and improved bone health.

Study Overview

• Status: Recruiting
• Conditions: Obesity; Diabetes; Metabolic Syndrome; Bone Diseases; Hyperlipidemias; Prostate Cancer; Cardiovascular Morbidity
• Intervention / Treatment: Drug: Apple Cider Vinegar

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Kaydee Connors; Phone Number: 56366 519-685-8500; Email: kaydee.connors@lhsc.on.ca
• Study Contact Backup: Name: Stephen Mardell; Phone Number: 58448 519-685-8500; Email: stephen.mardell@lhsc.on.ca

Study Locations

• Canada
  • Ontario
    • London, Ontario, Canada, N6A5W9
      • Recruiting
      • London Health Sciences Centre - Victoria Hospital

Participation Criteria

Eligibility Criteria

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

Description

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

1. 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).
2. Must have baseline imaging with 1) CT of the abdomen, and pelvis and bone scan or 2) PSMA PET scan

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

1. Age less than 18
2. Primary neuroendocrine prostate cancer
3. Treatment with ADT within the year leading up to enrolment
4. Planned or concurrent use of chromium supplementation for the study duration
5. Planned or concurrent use of apple cider vinegar supplementation for the study duration
6. Unable to provide informed consent or unable to understand or read the English language (unless accompanied by an interpreter)
7. Inadequate liver function (>2x upper limit of normal)
8. Any other condition, chronic disease, or lifestyle factor, that, in the opinion of the Qualified Investigator, may adversely affect the participant's ability to complete the study or its measures or pose significant risk to the participant
9. Use of antibiotics that cannot be discontinued for a washout period and remain off them for the duration of the trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Apple Cider Vinegar; Jamison apple cider vinegar caplets (NPN: 80078433). Each patient will be instructed to take 1 acetate caplet (equivalent of 143 mg/caplet containing 36% acetic acid) per day for 3 months.	Drug: Apple Cider Vinegar; Each patient will be instructed to take 1 caplet (equivalent of 143 mg/caplet containing 36% acetic acid) per day for 3 months (NPN: 80078433) https://www.jamiesonvitamins.com/products/apple-cider-vinegar-chromium?srsltid=AfmBOoqdVBFe83_5JM9BmkomQM1LqsJYSFTiP_78cnmehfzVg-4T4Z6o
No Intervention: Observation; Observation group will follow standard of care treatment.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Western University
• Investigators: Principal Investigator: Melissa Huynh, MD, Western University

Publications and helpful links

General Publications

• Keating NL, O'Malley AJ, Smith MR. Diabetes and cardiovascular disease during androgen deprivation therapy for prostate cancer. J Clin Oncol. 2006 Sep 20;24(27):4448-56. doi: 10.1200/JCO.2006.06.2497.
• Braga-Basaria M, Dobs AS, Muller DC, Carducci MA, John M, Egan J, Basaria S. Metabolic syndrome in men with prostate cancer undergoing long-term androgen-deprivation therapy. J Clin Oncol. 2006 Aug 20;24(24):3979-83. doi: 10.1200/JCO.2006.05.9741.
• Saigal CS, Gore JL, Krupski TL, Hanley J, Schonlau M, Litwin MS; Urologic Diseases in America Project. Androgen deprivation therapy increases cardiovascular morbidity in men with prostate cancer. Cancer. 2007 Oct 1;110(7):1493-500. doi: 10.1002/cncr.22933.
• D'Amico AV, Denham JW, Crook J, Chen MH, Goldhaber SZ, Lamb DS, Joseph D, Tai KH, Malone S, Ludgate C, Steigler A, Kantoff PW. Influence of androgen suppression therapy for prostate cancer on the frequency and timing of fatal myocardial infarctions. J Clin Oncol. 2007 Jun 10;25(17):2420-5. doi: 10.1200/JCO.2006.09.3369.
• Everard A, Belzer C, Geurts L, Ouwerkerk JP, Druart C, Bindels LB, Guiot Y, Derrien M, Muccioli GG, Delzenne NM, de Vos WM, Cani PD. Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. Proc Natl Acad Sci U S A. 2013 May 28;110(22):9066-71. doi: 10.1073/pnas.1219451110. Epub 2013 May 13.
• Efstathiou JA, Bae K, Shipley WU, Hanks GE, Pilepich MV, Sandler HM, Smith MR. Cardiovascular mortality after androgen deprivation therapy for locally advanced prostate cancer: RTOG 85-31. J Clin Oncol. 2009 Jan 1;27(1):92-9. doi: 10.1200/JCO.2007.12.3752. Epub 2008 Dec 1.
• Smith MR, Finkelstein JS, McGovern FJ, Zietman AL, Fallon MA, Schoenfeld DA, Kantoff PW. Changes in body composition during androgen deprivation therapy for prostate cancer. J Clin Endocrinol Metab. 2002 Feb;87(2):599-603. doi: 10.1210/jcem.87.2.8299.
• McKay RR, Feng FY, Wang AY, Wallis CJD, Moses KA. Recent Advances in the Management of High-Risk Localized Prostate Cancer: Local Therapy, Systemic Therapy, and Biomarkers to Guide Treatment Decisions. Am Soc Clin Oncol Educ Book. 2020 May;40:1-12. doi: 10.1200/EDBK_279459.
• Timilshina N, Breunis H, Alibhai SM. Impact of androgen deprivation therapy on weight gain differs by age in men with nonmetastatic prostate cancer. J Urol. 2012 Dec;188(6):2183-8. doi: 10.1016/j.juro.2012.08.018. Epub 2012 Oct 18.
• Seible DM, Gu X, Hyatt AS, Beard CJ, Choueiri TK, Efstathiou JA, Miyamoto DT, Mitin T, Martin NE, Sweeney CJ, Trinh QD, Beckman JA, Basaria S, Nguyen PL. Weight gain on androgen deprivation therapy: which patients are at highest risk? Urology. 2014 Jun;83(6):1316-21. doi: 10.1016/j.urology.2014.02.006. Epub 2014 Apr 13.
• Sturgeon KM, Deng L, Bluethmann SM, Zhou S, Trifiletti DM, Jiang C, Kelly SP, Zaorsky NG. A population-based study of cardiovascular disease mortality risk in US cancer patients. Eur Heart J. 2019 Dec 21;40(48):3889-3897. doi: 10.1093/eurheartj/ehz766.
• Jespersen CG, Norgaard M, Borre M. Androgen-deprivation therapy in treatment of prostate cancer and risk of myocardial infarction and stroke: a nationwide Danish population-based cohort study. Eur Urol. 2014 Apr;65(4):704-9. doi: 10.1016/j.eururo.2013.02.002. Epub 2013 Feb 12.
• Voog JC, Paulus R, Shipley WU, Smith MR, McGowan DG, Jones CU, Bahary JP, Zeitzer KL, Souhami L, Leibenhaut MH, Rotman M, Husain SM, Gore E, Raben A, Chafe S, Sandler HM, Efstathiou JA. Cardiovascular Mortality Following Short-term Androgen Deprivation in Clinically Localized Prostate Cancer: An Analysis of RTOG 94-08. Eur Urol. 2016 Feb;69(2):204-10. doi: 10.1016/j.eururo.2015.08.027. Epub 2015 Sep 9.
• Grossmann M, Hamilton EJ, Gilfillan C, Bolton D, Joon DL, Zajac JD. Bone and metabolic health in patients with non-metastatic prostate cancer who are receiving androgen deprivation therapy. Med J Aust. 2011 Mar 21;194(6):301-6. doi: 10.5694/j.1326-5377.2011.tb02979.x.
• Morote J, Orsola A, Abascal JM, Planas J, Trilla E, Raventos CX, Cecchini L, Encabo G, Reventos J. Bone mineral density changes in patients with prostate cancer during the first 2 years of androgen suppression. J Urol. 2006 May;175(5):1679-83; discussion 1683. doi: 10.1016/S0022-5347(05)00999-7.
• Smith MR, Lee WC, Brandman J, Wang Q, Botteman M, Pashos CL. Gonadotropin-releasing hormone agonists and fracture risk: a claims-based cohort study of men with nonmetastatic prostate cancer. J Clin Oncol. 2005 Nov 1;23(31):7897-903. doi: 10.1200/JCO.2004.00.6908.
• van der Beek CM, Canfora EE, Lenaerts K, Troost FJ, Damink SWMO, Holst JJ, Masclee AAM, Dejong CHC, Blaak EE. Distal, not proximal, colonic acetate infusions promote fat oxidation and improve metabolic markers in overweight/obese men. Clin Sci (Lond). 2016 Nov 1;130(22):2073-2082. doi: 10.1042/CS20160263. Epub 2016 Jul 20.
• Perraudeau F, McMurdie P, Bullard J, Cheng A, Cutcliffe C, Deo A, Eid J, Gines J, Iyer M, Justice N, Loo WT, Nemchek M, Schicklberger M, Souza M, Stoneburner B, Tyagi S, Kolterman O. Improvements to postprandial glucose control in subjects with type 2 diabetes: a multicenter, double blind, randomized placebo-controlled trial of a novel probiotic formulation. BMJ Open Diabetes Res Care. 2020 Jul;8(1):e001319. doi: 10.1136/bmjdrc-2020-001319.
• Zhou Q, Zhang Y, Wang X, Yang R, Zhu X, Zhang Y, Chen C, Yuan H, Yang Z, Sun L. Gut bacteria Akkermansia is associated with reduced risk of obesity: evidence from the American Gut Project. Nutr Metab (Lond). 2020 Oct 22;17:90. doi: 10.1186/s12986-020-00516-1. eCollection 2020.
• Luna M, Guss JD, Vasquez-Bolanos LS, Castaneda M, Rojas MV, Strong JM, Alabi DA, Dornevil SD, Nixon JC, Taylor EA, Donnelly E, Fu X, Shea MK, Booth SL, Bicalho R, Hernandez CJ. Components of the Gut Microbiome That Influence Bone Tissue-Level Strength. J Bone Miner Res. 2021 Sep;36(9):1823-1834. doi: 10.1002/jbmr.4341. Epub 2021 Jun 4.
• Booth SL, Tucker KL, Chen H, Hannan MT, Gagnon DR, Cupples LA, Wilson PW, Ordovas J, Schaefer EJ, Dawson-Hughes B, Kiel DP. Dietary vitamin K intakes are associated with hip fracture but not with bone mineral density in elderly men and women. Am J Clin Nutr. 2000 May;71(5):1201-8. doi: 10.1093/ajcn/71.5.1201.
• Evenepoel P, Dejongh S, Verbeke K, Meijers B. The Role of Gut Dysbiosis in the Bone-Vascular Axis in Chronic Kidney Disease. Toxins (Basel). 2020 Apr 29;12(5):285. doi: 10.3390/toxins12050285.
• Mandatori D, Pelusi L, Schiavone V, Pipino C, Di Pietro N, Pandolfi A. The Dual Role of Vitamin K2 in "Bone-Vascular Crosstalk": Opposite Effects on Bone Loss and Vascular Calcification. Nutrients. 2021 Apr 7;13(4):1222. doi: 10.3390/nu13041222.
• Arrieta MC, Bistritz L, Meddings JB. Alterations in intestinal permeability. Gut. 2006 Oct;55(10):1512-20. doi: 10.1136/gut.2005.085373. No abstract available.
• Kokorovic A, So AI, Serag H, French C, Hamilton RJ, Izard JP, Nayak JG, Pouliot F, Saad F, Shayegan B, Aprikian A, Rendon RA. Canadian Urological Association guideline on androgen deprivation therapy: Adverse events and management strategies. Can Urol Assoc J. 2021 Jun;15(6):E307-E322. doi: 10.5489/cuaj.7355. No abstract available.
• Daisley BA, Chanyi RM, Abdur-Rashid K, Al KF, Gibbons S, Chmiel JA, Wilcox H, Reid G, Anderson A, Dewar M, Nair SM, Chin J, Burton JP. Abiraterone acetate preferentially enriches for the gut commensal Akkermansia muciniphila in castrate-resistant prostate cancer patients. Nat Commun. 2020 Sep 24;11(1):4822. doi: 10.1038/s41467-020-18649-5.

Study record dates

Study Major Dates

• Study Start (Actual): July 2, 2025
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: March 12, 2023
• First Submitted That Met QC Criteria: March 24, 2023
• First Posted (Actual): April 6, 2023

Study Record Updates

• Last Update Posted (Actual): August 20, 2025
• Last Update Submitted That Met QC Criteria: August 15, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: prostate cancer; cardiovascular disease; metabolic syndrome; microbiome; androgen deprivation therapy; Akkermansias muciniphilia
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Musculoskeletal Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Metabolic Diseases; Glucose Metabolism Disorders; Insulin Resistance; Hyperinsulinism; Dyslipidemias; Lipid Metabolism Disorders; Prostatic Neoplasms; Metabolic Syndrome; Bone Diseases; Hyperlipidemias; Anti-Bacterial Agents; Anti-Infective Agents; Acetic Acid
• Other Study ID Numbers: ReDA ID 12558

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Our study protocol and analyses can be shared, but individual data will not.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No