Monitoring the Effects of Probiotic Supplementation in Immunocompromised Kidney Transplanted Subjects

NCT05102461 | Withdrawn

• 1 other identifier: 1424802
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

In order to protect their new renal graft, post-transplant patients follow a rigorous immunosuppressive therapy combined with prophylactic antibiotic treatment. Kidney transplant recipients are prescribed long-term immunosuppression maintenance regimens that are the prophylaxis of organ rejection. The most frequently used are calcineurin inhibitors (tacrolimus or cyclosporine) combined with glucocorticoids (methylprednisolone, prednisone) and antiproliferative agents (mycophenolate mofetil, azathioprine). However, the use of immunosuppressive medication in transplanted patients have well-documented limitations. Recent studies reported major changes in microbiota composition as a result of immunosuppression use. A large majority of transplant patients develops severe GI problems, with the most common complication being post-transplant diarrhea. Several studies have assessed and confirmed negative effects of post-transplant diarrhea. According to (3, 4), post-transplant diarrhea affects 1 in 5 patients in the first year after kidney transplantation and is associated with decreased quality of life, allograft failure, and even death.

Conditions

Diarrhea Caused by Drug; Dysbiosis

Keywords

Post-Transplant Diarrhea; Gastrointestinal Symptoms; Immunosuppression Acquired Diarrhea (IAD); Probiotic Supplementation

Outcome Measures

Primary Outcomes (2)

• To investigate if daily use of low dose probiotics is effective in alleviating symptoms of diarrhea in post-transplant subjects

  Does a small dose of daily probiotic supplementation improve the quality of life for kidney transplanted patients? Reduction and correction of diarrhea will be measured by \<3 well-formed daily bowel movements, \<200 grams of daily stool, and \<75-85% fecal water content.

  180 days

• Correlation of probiotic use with pro-inflammatory, inflammatory, and anti-inflammatory biomarkers

  Does probiotic supplementation lower pro-inflammatory and inflammatory biomarkers while increasing anti-inflammatory biomarkers in renal transplant recipients? Pro-inflammatory cytokines: Interleukin (IL)-1, IL-12, IL-13, IL-17A, tumor necrosis factor (TNF)-α and interferon (INF)-γ Inflammatory and anti-inflammatory cytokines: IL-6 and IL-4, and IL-10, respectively. Reduction and increments will be measured by the lowering or increasing of serum cytokine by 20% from baseline

  180 days

Secondary Outcomes (1)

• To characterize microbiota in subjects with and without diarrhea

  180 days

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Subjects randomized in the Placebo Arm will take one placebo capsule daily. Each capsule will also contain 32 mg of riboflavin as a tracer substance for tracking compliance.

Dietary Supplement: Placebo Supplementation

Treatment

ACTIVE COMPARATOR

Subjects randomized in the Treatment Arm will take one placebo capsule daily. One Florajen Digestion capsule contains 15 billion live cultures of Lactobacillus acidophilus (7.5 billion), Bifodobacterium lactis (6.0 billion), and Bifidobacterium longum (1.5 billion). Each capsule will also contain 32 mg of riboflavin as a tracer substance for tracking compliance.

Dietary Supplement: Florajen Digestion Supplementation

Interventions

Florajen Digestion Supplementation DIETARY_SUPPLEMENT

Subjects will take the placebo starting from Week 3 post-transplant until 180 days after transplant. Compliance will be measured through the return of empty packs and urinalysis for riboflavin during follow-up visits in clinic.

Treatment

Placebo Supplementation DIETARY_SUPPLEMENT

Subjects will take Florajen Digestion starting from Week 3 post-transplant until 180 days after transplant. Compliance will be measured through the return of empty packs and urinalysis for riboflavin during follow-up visits in clinic.

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Recipient of a living or deceased donor kidney transplant
• Maintenance of a therapeutic dose of Mycophenolate Mofetil (MMF) and Tacrolimus after transplant
• No other gastrointestinal issues

You may not qualify if:

• Currently pregnant and lactating
• Has been receiving probiotics supplementation other than the study designated formula
• Participation in a different clinical trial
• Positive infection of Clostridium difficile and/or rotavirus as analyzed by stool culture

Sponsors & Collaborators

• State University of New York - Upstate Medical University: lead

Study Sites (1)

SUNY Upstate Medical University

Syracuse, New York, 13210, United States

Location

Related Publications (3)

• Lee JR, Magruder M, Zhang L, Westblade LF, Satlin MJ, Robertson A, Edusei E, Crawford C, Ling L, Taur Y, Schluter J, Lubetzky M, Dadhania D, Pamer E, Suthanthiran M. Gut microbiota dysbiosis and diarrhea in kidney transplant recipients. Am J Transplant. 2019 Feb;19(2):488-500. doi: 10.1111/ajt.14974. Epub 2018 Jul 21.

  PMID: 29920927 BACKGROUND

• Ekberg H, Kyllonen L, Madsen S, Grave G, Solbu D, Holdaas H. Increased prevalence of gastrointestinal symptoms associated with impaired quality of life in renal transplant recipients. Transplantation. 2007 Feb 15;83(3):282-9. doi: 10.1097/01.tp.0000251923.14697.f5.

  PMID: 17297402 BACKGROUND

• Bunnapradist S, Neri L, Wong W, Lentine KL, Burroughs TE, Pinsky BW, Takemoto SK, Schnitzler MA. Incidence and risk factors for diarrhea following kidney transplantation and association with graft loss and mortality. Am J Kidney Dis. 2008 Mar;51(3):478-86. doi: 10.1053/j.ajkd.2007.11.013.

  PMID: 18295064 BACKGROUND

MeSH Terms

Conditions

Dysbiosis

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Mark R Laftavi, MD

  State University of New York - Upstate Medical University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: A statistician will provide the randomization scheme to the unblinded pharmacy research staff who will carry out the process. The chance that subjects will receive Florajen Digestion or the placebo will be 1:1.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a randomized, double-blinded, placebo-controlled study in SUNY Upstate University Hospital's Department of Surgery/Transplant Division. The total number of subjects enrolled will be 70 for both arms - placebo, 35 and treatment, 35. In order to eliminate bias, subjects will be randomized into two groups (treatment and placebo) using block randomization.

Study Record Dates

• First Submitted: October 19, 2021
• First Posted: November 1, 2021
• Study Start: July 1, 2020
• Primary Completion: October 1, 2022
• Study Completion: October 1, 2025
• Last Updated: November 1, 2021

Record last verified: 2020-08

Locations

US (1)