Akkermansia Muciniphilia and Metabolic Side Effects of ADT

NCT05802121 | Recruiting Early Phase 1 DMC

• 1 other identifier: ReDA ID 12558
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The overriding objectives of this study are:

1. 1.Primary outcomes:
2. 2.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.
3. 3.To confirm tolerability and assess for side effects of oral acetate supplementation.
4. 4.Secondary outcomes:
5. 5.To determine if increased counts of A. muciniphilia correlate with improved metabolic parameters and improved bone health.

Conditions

Prostate Cancer; Metabolic Syndrome; Obesity; Cardiovascular Morbidity; Bone Diseases; Hyperlipidemias; Diabetes

Keywords

prostate cancer; metabolic syndrome; androgen deprivation therapy; microbiome; Akkermansias muciniphilia; cardiovascular disease

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (29)

• Metabolic parameters: fasting plasma glucose

  3 months

• Metabolic parameters: fasting plasma glucose

  6 months

• Metabolic parameters: HbA1C

  3 months

• Metabolic parameters: HbA1c

  6 months

• Metabolic parameters: triglycerides

  3 months

Study Arms (2)

Apple Cider Vinegar

EXPERIMENTAL

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

Observation

NO INTERVENTION

Observation group will follow standard of care treatment.

Interventions

Apple Cider Vinegar DRUG

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

Apple Cider Vinegar

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Western University: lead

Study Sites (1)

London Health Sciences Centre - Victoria Hospital

London, Ontario, N6A5W9, Canada

RECRUITING

Related Publications (26)

• 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.

  PMID: 32412803 BACKGROUND

• 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.

  PMID: 11836291 BACKGROUND

• 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.

  PMID: 23083859 BACKGROUND

• 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.

  PMID: 16921050 BACKGROUND

• 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.

  PMID: 24726149 BACKGROUND

• 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.

  PMID: 31761945 BACKGROUND

• 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.

  PMID: 17657815 BACKGROUND

• 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.

  PMID: 16983113 BACKGROUND

• 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.

  PMID: 23433805 BACKGROUND

• 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.

  PMID: 17557956 BACKGROUND

• 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.

  PMID: 26362090 BACKGROUND

• 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.

  PMID: 19047297 BACKGROUND

• 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.

  PMID: 21426285 BACKGROUND

• 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.

  PMID: 16600728 BACKGROUND

• 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.

  PMID: 16258089 BACKGROUND

• 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.

  PMID: 34127184 BACKGROUND

• 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.

  PMID: 32973149 BACKGROUND

• 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.

  PMID: 27439969 BACKGROUND

• 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.

  PMID: 23671105 BACKGROUND

• 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.

  PMID: 32675291 BACKGROUND

• 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.

  PMID: 33110437 BACKGROUND

• 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.

  PMID: 33999456 BACKGROUND

• 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.

  PMID: 10799384 BACKGROUND

• 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.

  PMID: 32365480 BACKGROUND

• 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.

  PMID: 33917175 BACKGROUND

• 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.

  PMID: 16966705 BACKGROUND

MeSH Terms

Conditions

Prostatic Neoplasms; Metabolic Syndrome; Obesity; Bone Diseases; Hyperlipidemias; Diabetes Mellitus; Cardiovascular Diseases

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Musculoskeletal Diseases; Dyslipidemias; Lipid Metabolism Disorders; Endocrine System Diseases

Study Officials

• Melissa Huynh, MD

  Western University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kaydee Connors

CONTACT

519-685-8500; kaydee.connors@lhsc.on.ca

Stephen Mardell

CONTACT

519-685-8500; stephen.mardell@lhsc.on.ca

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: This will be a single-institution, randomized 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 either conventional imaging (CT and BS) or PSMA PET scan. Patients will be randomized 1:1 to receive acetate supplementation or observation. 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.

Study Record Dates

• First Submitted: March 12, 2023
• First Posted: April 6, 2023
• Study Start: July 2, 2025
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): June 1, 2027
• Last Updated: August 20, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)