Prebiotic Therapy to Improve Outcomes of Renal Transplant

NCT04428190 | Unknown Early Phase 1

• 1 other identifier: PRT01
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

An investigator initiated pilot study: two arm, double blind, placebo controlled, randomized, group of approximately 60 patients undergoing a kidney transplant. Participants will be treated with human milk oligosaccharide (HMO) prebiotic versus placebo over 12 weeks from start of the investigational medication date (approximately 3 months) to test whether HMO can improve renal transplant outcomes. Participants will be followed up for 3 months after after they complete the treatment portion of the study. HMO sachets will be administered to determine the safety and efficacy of HMO relative to placebo in improving renal transplant outcomes in patients by reducing delayed graft function and side effects from post transplant therapy.

Conditions

Kidney Transplant; Complications

Keywords

kidney; kidney transplant; prebiotic; human milk oligosaccharide; HMO; renal transplant

Outcome Measures

Primary Outcomes (2)

• Short Form Health Survey (SF-36)

  The Short Form Health Survey will measure participant satisfaction using a scale from 1 - 5, 1 being the best outcome, and 5 being the worst outcome.

  24 weeks

• Adverse Events

  Adverse events will be recorded through case report forms and reported to the principal investigator. Side effects will be assessed using standardized case report forms at each visit. Participants are encouraged to contact the coordinator to report any concerns.

  24 weeks

Secondary Outcomes (2)

• Microbiome changes from baseline to end of treatment

  12 weeks

• Microbiome changes post intervention

  12 weeks

Other Outcomes (14)

• Number of participants who experience kidney rejection

  24 weeks

• Immunosuppression suppressive drug dose

  post-operative day 1, 7, 30, 60, 90, 120, 150 and 180

• Infectious complications

  post-operative day 30, 60, 90, 120, 150 and 180.

Study Arms (2)

Human Milk Oligosaccharide (HMO)

ACTIVE COMPARATOR

10 g sachet, self-administered for 3 months. 2'-O-fucosyllactose and lacto-N-neotetraose, novel human milk oligosaccharide (HMO) sugars have been shown to stimulate the production of short chain fatty acids, especially propionate. Propionate has been shown to be important in attenuating hypertrophy, fibrosis, vascular dysfunction and hypertension (Bartolomaeus H et al 2019Mar12) and extremely important for the gut kidney axis (Li L et al 2017Dec11).

Dietary Supplement: Human Milk Oligosaccharides (HMO)

Placebo

PLACEBO COMPARATOR

10 g sachet, self-administered for 3 months. Placebo sachets are identical to the HMO sachets in color, taste, smell, size and shape

Other: Placebo

Interventions

Human Milk Oligosaccharides (HMO) DIETARY_SUPPLEMENT

Sachet containing 10 grams of HMO

Also known as: Prebiotic

Human Milk Oligosaccharide (HMO)

Placebo OTHER

Sachet manufactured to mimic 10g of HMO

Also known as: Placebo for HMO

Placebo

Eligibility Criteria

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

You may qualify if:

• years of age and over receiving a kidney transplant.

You may not qualify if:

• Under 18 years of age
• Inability to give consent
• Usage of probiotics or other prebiotics.
• Have had carcinomas during the last 5 years
• Bowel surgery
• Crohn ́s disease and other conditions.

Sponsors & Collaborators

• London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's: lead
• The W. Garfield Weston Foundation: collaborator
• St. Joseph's Health Care London: collaborator
• London Health Sciences Centre: collaborator

Study Sites (1)

London Health Sciences Centre

London, Ontario, N6A 5A5, Canada

RECRUITING

Related Publications (15)

• Pluznick JL. Gut microbiota in renal physiology: focus on short-chain fatty acids and their receptors. Kidney Int. 2016 Dec;90(6):1191-1198. doi: 10.1016/j.kint.2016.06.033. Epub 2016 Aug 26.

  PMID: 27575555 BACKGROUND

• Lee JR, Muthukumar T, Dadhania D, Taur Y, Jenq RR, Toussaint NC, Ling L, Pamer E, Suthanthiran M. Gut microbiota and tacrolimus dosing in kidney transplantation. PLoS One. 2015 Mar 27;10(3):e0122399. doi: 10.1371/journal.pone.0122399. eCollection 2015.

  PMID: 25815766 BACKGROUND

• Elison E, Vigsnaes LK, Rindom Krogsgaard L, Rasmussen J, Sorensen N, McConnell B, Hennet T, Sommer MO, Bytzer P. Oral supplementation of healthy adults with 2'-O-fucosyllactose and lacto-N-neotetraose is well tolerated and shifts the intestinal microbiota. Br J Nutr. 2016 Oct;116(8):1356-1368. doi: 10.1017/S0007114516003354. Epub 2016 Oct 10.

  PMID: 27719686 BACKGROUND

• Harvie RM, Chisholm AW, Bisanz JE, Burton JP, Herbison P, Schultz K, Schultz M. Long-term irritable bowel syndrome symptom control with reintroduction of selected FODMAPs. World J Gastroenterol. 2017 Jul 7;23(25):4632-4643. doi: 10.3748/wjg.v23.i25.4632.

  PMID: 28740352 BACKGROUND

• Dubberke ER, Riddle DJ; AST Infectious Diseases Community of Practice. Clostridium difficile in solid organ transplant recipients. Am J Transplant. 2009 Dec;9 Suppl 4(0 4):S35-40. doi: 10.1111/j.1600-6143.2009.02891.x.

  PMID: 20070693 BACKGROUND

• Rayes N, Seehofer D, Theruvath T, Schiller RA, Langrehr JM, Jonas S, Bengmark S, Neuhaus P. Supply of pre- and probiotics reduces bacterial infection rates after liver transplantation--a randomized, double-blind trial. Am J Transplant. 2005 Jan;5(1):125-30. doi: 10.1111/j.1600-6143.2004.00649.x.

  PMID: 15636620 BACKGROUND

• Sawas T, Al Halabi S, Hernaez R, Carey WD, Cho WK. Patients Receiving Prebiotics and Probiotics Before Liver Transplantation Develop Fewer Infections Than Controls: A Systematic Review and Meta-Analysis. Clin Gastroenterol Hepatol. 2015 Sep;13(9):1567-74.e3; quiz e143-4. doi: 10.1016/j.cgh.2015.05.027. Epub 2015 Jun 2.

  PMID: 26044318 BACKGROUND

• Lobb I, Jiang J, Lian D, Liu W, Haig A, Saha MN, Torregrossa R, Wood ME, Whiteman M, Sener A. Hydrogen Sulfide Protects Renal Grafts Against Prolonged Cold Ischemia-Reperfusion Injury via Specific Mitochondrial Actions. Am J Transplant. 2017 Feb;17(2):341-352. doi: 10.1111/ajt.14080. Epub 2016 Nov 29.

  PMID: 27743487 BACKGROUND

• Al KF, Bisanz JE, Gloor GB, Reid G, Burton JP. Evaluation of sampling and storage procedures on preserving the community structure of stool microbiota: A simple at-home toilet-paper collection method. J Microbiol Methods. 2018 Jan;144:117-121. doi: 10.1016/j.mimet.2017.11.014. Epub 2017 Nov 16.

  PMID: 29155236 BACKGROUND

• Bao Y, Al KF, Chanyi RM, Whiteside S, Dewar M, Razvi H, Reid G, Burton JP. Questions and challenges associated with studying the microbiome of the urinary tract. Ann Transl Med. 2017 Jan;5(2):33. doi: 10.21037/atm.2016.12.14.

  PMID: 28217698 BACKGROUND

• Perico N, Cattaneo D, Sayegh MH, Remuzzi G. Delayed graft function in kidney transplantation. Lancet. 2004 Nov 13-19;364(9447):1814-27. doi: 10.1016/S0140-6736(04)17406-0.

  PMID: 15541456 RESULT

• Wong J, Piceno YM, DeSantis TZ, Pahl M, Andersen GL, Vaziri ND. Expansion of urease- and uricase-containing, indole- and p-cresol-forming and contraction of short-chain fatty acid-producing intestinal microbiota in ESRD. Am J Nephrol. 2014;39(3):230-237. doi: 10.1159/000360010. Epub 2014 Mar 8.

  PMID: 24643131 RESULT

• Bartolomaeus H, Balogh A, Yakoub M, Homann S, Marko L, Hoges S, Tsvetkov D, Krannich A, Wundersitz S, Avery EG, Haase N, Kraker K, Hering L, Maase M, Kusche-Vihrog K, Grandoch M, Fielitz J, Kempa S, Gollasch M, Zhumadilov Z, Kozhakhmetov S, Kushugulova A, Eckardt KU, Dechend R, Rump LC, Forslund SK, Muller DN, Stegbauer J, Wilck N. Short-Chain Fatty Acid Propionate Protects From Hypertensive Cardiovascular Damage. Circulation. 2019 Mar 12;139(11):1407-1421. doi: 10.1161/CIRCULATIONAHA.118.036652.

  PMID: 30586752 RESULT

• Li L, Ma L, Fu P. Gut microbiota-derived short-chain fatty acids and kidney diseases. Drug Des Devel Ther. 2017 Dec 11;11:3531-3542. doi: 10.2147/DDDT.S150825. eCollection 2017.

  PMID: 29270002 RESULT

• Cooper TE, Scholes-Robertson N, Craig JC, Hawley CM, Howell M, Johnson DW, Teixeira-Pinto A, Jaure A, Wong G. Synbiotics, prebiotics and probiotics for solid organ transplant recipients. Cochrane Database Syst Rev. 2022 Sep 20;9(9):CD014804. doi: 10.1002/14651858.CD014804.pub2.

  PMID: 36126902 DERIVED

MeSH Terms

Interventions

Prebiotics; Health Maintenance Organizations

Intervention Hierarchy (Ancestors)

Dietary Fiber; Dietary Carbohydrates; Carbohydrates; Polysaccharides, Bacterial; Polysaccharides; Food; Diet, Food, and Nutrition; Physiological Phenomena; Dietary Supplements; Food and Beverages; Managed Care Programs; Insurance, Health; Insurance; Financing, Organized; Economics; Health Care Economics and Organizations; Prepaid Health Plans; Group Practice; Professional Practice; Organization and Administration; Health Services Administration; Delivery of Health Care; Patient Care Management

Study Officials

• Alp Sener, MD

  London Health Sciences Centre

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mounirah May

CONTACT

519-685-8500; mounirah.may@lhsc.on.ca

Jeremy P Burton, PhD

CONTACT

519-646-6000; Jeremy.Burton@LawsonResearch.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: No other parties will be masked for the study.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: One placebo arm and one active treatment arm, participants will be assigned to each arm equally.

Study Record Dates

• First Submitted: May 28, 2020
• First Posted: June 11, 2020
• Study Start: February 23, 2022
• Primary Completion: October 15, 2024
• Study Completion: December 15, 2024
• Last Updated: November 1, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)