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The overriding objectives of this study are:
Primary outcomes:
Secondary outcomes:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| Observation | No Intervention | Observation group will follow standard of care treatment. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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) |
| 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 |
| 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) |
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For inclusion in this study, patients must fulfill all of the following criteria:
Patients fulfilling any of the following criteria are NOT eligible for participation in this study:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Kaydee Connors | Contact | 519-685-8500 | 56366 | kaydee.connors@lhsc.on.ca |
| Stephen Mardell | Contact | 519-685-8500 | 58448 | stephen.mardell@lhsc.on.ca |
| Name | Affiliation | Role |
|---|---|---|
| Melissa Huynh, MD | Western University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| London Health Sciences Centre - Victoria Hospital | Recruiting | London | Ontario | N6A5W9 | Canada |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32412803 | Background | 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. | |
| 11836291 | 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. |
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Our study protocol and analyses can be shared, but individual data will not.
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| ID | Term |
|---|---|
| D011471 | Prostatic Neoplasms |
| D024821 | Metabolic Syndrome |
| D009765 | Obesity |
| D001847 | Bone Diseases |
| D006949 | Hyperlipidemias |
| D003920 | Diabetes Mellitus |
| D002318 | Cardiovascular Diseases |
| ID | Term |
|---|---|
| D005834 | Genital Neoplasms, Male |
| D014565 | Urogenital Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
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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.
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|
| 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 |
| 23083859 | 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. |
| 16921050 | 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. |
| 24726149 | 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. |
| 31761945 | 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. |
| 17657815 | 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. |
| 16983113 | 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. |
| 23433805 | 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. |
| 17557956 | 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. |
| 26362090 | 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. |
| 19047297 | 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. |
| 21426285 | 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. |
| 16600728 | 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. |
| 16258089 | 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. |
| 34127184 | 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. |
| 32973149 | 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. |
| 27439969 | 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. |
| 23671105 | 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. |
| 32675291 | 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. |
| 33110437 | 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. |
| 33999456 | 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. |
| 10799384 | 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. |
| 32365480 | 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. |
| 33917175 | 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. |
| 16966705 | 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. |
| D005832 |
| Genital Diseases, Male |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D011469 | Prostatic Diseases |
| D052801 | Male Urogenital Diseases |
| D007333 | Insulin Resistance |
| D006946 | Hyperinsulinism |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D050177 | Overweight |
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D001835 | Body Weight |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D009140 | Musculoskeletal Diseases |
| D050171 | Dyslipidemias |
| D052439 | Lipid Metabolism Disorders |
| D004700 | Endocrine System Diseases |