Diarrhea Caused by DrugNCT05102461
Monitoring the Effects of Probiotic Supplementation in Immunocompromised Kidney Transplanted Subjects
A study testing Florajen Digestion Supplementation in people with Diarrhea Caused by Drug and Dysbiosis, run by State University of New York - Upstate Medical University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Diarrhea Caused by Drug, Dysbiosis
- What is being tested?
- Florajen Digestion Supplementation
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2020to Oct 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
SUNY Upstate Medical University
Syracuse, New York, 13210
About this study
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.
Read the detailed description
Challenges faced by patients after kidney transplantation prompted providers to look for additional strategies to improve their quality of life and decrease graft risks. In daily practice, investigators noted that a good percentage of transplant patients develops gastrointestinal (GI) symptoms, particularly diarrhea. In literature, this is known as Immunosuppression Acquired Diarrhea (IAD). These episodes are especially distressing and usually lead to immunosuppressive medication being reduced in dose or stopped. As a result of these actions, transplant patients become exposed to rejection, graft loss, and even death. Considering how the microbiota is altered during the post-transplant medication regimen, restoring the gut balance through the administration of probiotics presents a suitable solution. The proposed research would help increase knowledge on the beneficial effects and safety of probiotics in post-transplant patients.
Diarrhea is a very common and severe complication in post-transplant patients. In the majority of the cases, it is categorized as unspecified noninfectious diarrhea (1, 3). Transplant physicians associate it with immunosuppressive drugs such as mycophenolate mofetil (MMF) (7) and other agents such as tacrolimus, azathioprine, and adrenal corticosteroids that are the prophylaxis of organ rejection in patients receiving allogenic renal transplants.
The most common strategy to reduce post-transplant noninfectious diarrhea is the reduction of MMF dosing (4). Many times, the diarrhea events are so severe that the recipient's immunosuppressive medications are tapered, changed or stopped. As a result, patients become at risk of early acute rejection and graft loss.
There is a large body of literature that offers information about the etiology of diarrhea for these patients. The main cause is an alteration in microbiota composition - a condition known as dysbiosis. Offering great insight, Swarat et al., (8) wrote, "the microbiota is able to induce disease (10, 12) and also able to regulate immunity or tolerance. An imbalance between pathogenic and protective microbes characterizes dysbiosis, a perturbation in the normal composition of commensal microbiota". In the post-transplant patient population, the immunosuppressive regimen and use of prophylactic antimicrobial treatments create new post-transplant microbiota communities. In literature, dysbiosis is associated with clinical conditions and systematic inflammation.
Four main phyla found in the GI tract are known to contribute to human health and disease: Firmicutes, Bacteroidetes, Actinobacteria, and Proteobacteria, with the majority of species being non-pathogenic [13]. These commensal microbes play an important role in immune regulation, nutrition, and maintenance of host barriers against pathogens [14, 15]. It was reported that during diarrhea episodes (dysbiosis) in post-transplant patients, there is an increase in Proteobacteria and a decrease in Bacteroides, Ruminococcus, Coprococcus, and Dorea.
Although there are clinical trials offering information about microbiota composition in patients with diarrhea, there is not much information that links it to probiotic use after kidney transplantation.
The main objectives of this clinical trial are:
- To investigate if daily use of low dose probiotics is effective in alleviating symptoms of diarrhea as well as lowering pro-inflammatory and inflammatory biomarkers and increasing anti-inflammatory biomarkers in renal transplant recipients.
- To characterize microbiota in subjects with and without diarrhea and determine if there is any correlation between microbiota content and pro-inflammatory, inflammatory, and anti-inflammatory biomarkers.
- Conditions
- Diarrhea Caused by Drug, Dysbiosis
- Being tested
- Florajen Digestion Supplementation, Placebo Supplementation
- Keywords
- Post-Transplant Diarrhea, Gastrointestinal Symptoms, Immunosuppression Acquired Diarrhea (IAD), Probiotic Supplementation
- Medical subject headings
- Dysbiosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Florajen Digestion SupplementationDietary 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.
Placebo SupplementationDietary 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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Dietary Supplement: Florajen Digestion Supplementation |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Measured: 180 days
Secondary outcomes (1)
To characterize microbiota in subjects with and without diarrhea
Positive correlations will exist between "good" fecal microbiota content shifts and reductions in serum pro-inflammatory cytokine values. "Good" fecal microbiota shifts are defined as increases in Firmicutes, Bacteroides, Ruminococcus, Coprococcus, and Dorea and decreases in Protobacteria.
Measured: 180 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Nov 2021
- Study startJul 2020 (estimated)
- Primary completionOct 2022 (estimated)
- Study completionOct 2025 (estimated)
Why it stopped: It wasn't approved for using Florajen as a dietary supplement and the supplier did not support the application for an IND
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Diarrhea Caused by DrugStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- State University of New York - Upstate Medical University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Mark R Laftavi, MD, Principal investigator, State University of New York - Upstate Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05102461
- Sponsor's protocol ID
- 1424802
- Status last verified
- Aug 2020
- First submitted
- 19 Oct 2021
- Last updated
- 1 Nov 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 29920927Ekberg 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.
PubMed 17297402Bunnapradist 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.
PubMed 18295064
Study at a glance
From the registry record, last updated by the sponsor on 1 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Monitoring the Effects of Probiotic Supplementation in Immunocompromised Kidney Transplanted Subjects
- ClinicalTrials.gov ID
- NCT05102461
- Acronym / sponsor ID
- 1424802
- Conditions
- Diarrhea Caused by Drug, Dysbiosis
- Keywords
- Post-Transplant Diarrhea, Gastrointestinal Symptoms, Immunosuppression Acquired Diarrhea (IAD), Probiotic Supplementation
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: It wasn't approved for using Florajen as a dietary supplement and the supplier did not support the application for an IND
- Enrolment
- 0 participants (actual)
- Lead sponsor
- State University of New York - Upstate Medical UniversityUniversity, hospital or other
- Study start
- Jul 2020 (estimated)
- Primary completion
- Oct 2022 (estimated)
- Study completion
- Oct 2025 (estimated)
- First posted
- 1 Nov 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Challenges faced by patients after kidney transplantation prompted providers to look for additional strategies to improve their quality of life and decrease graft risks. In daily practice, investigators noted that a good percentage of transplant patients develops gastrointestinal (GI) symptoms, particularly diarrhea. In literature, this is known as Immunosuppression Acquired Diarrhea (IAD). These episodes are especially distressing and usually lead to immunosuppressive medication being reduced in dose or stopped. As a result of these actions, transplant patients become exposed to rejection, graft loss, and even death. Considering how the microbiota is altered during the post-transplant medication regimen, restoring the gut balance through the administration of probiotics presents a suitable solution. The proposed research would help increase knowledge on the beneficial effects and safety of probiotics in post-transplant patients.
Diarrhea is a very common and severe complication in post-transplant patients. In the majority of the cases, it is categorized as unspecified noninfectious diarrhea (1, 3). Transplant physicians associate it with immunosuppressive drugs such as mycophenolate mofetil (MMF) (7) and other agents such as tacrolimus, azathioprine, and adrenal corticosteroids that are the prophylaxis of organ rejection in patients receiving allogenic renal transplants.
The most common strategy to reduce post-transplant noninfectious diarrhea is the reduction of MMF dosing (4). Many times, the diarrhea events are so severe that the recipient's immunosuppressive medications are tapered, changed or stopped. As a result, patients become at risk of early acute rejection and graft loss.
There is a large body of literature that offers information about the etiology of diarrhea for these patients. The main cause is an alteration in microbiota composition - a condition known as dysbiosis. Offering great insight, Swarat et al., (8) wrote, "the microbiota is able to induce disease (10, 12) and also able to regulate immunity or tolerance. An imbalance between pathogenic and protective microbes characterizes dysbiosis, a perturbation in the normal composition of commensal microbiota". In the post-transplant patient population, the immunosuppressive regimen and use of prophylactic antimicrobial treatments create new post-transplant microbiota communities. In literature, dysbiosis is associated with clinical conditions and systematic inflammation.
Four main phyla found in the GI tract are known to contribute to human health and disease: Firmicutes, Bacteroidetes, Actinobacteria, and Proteobacteria, with the majority of species being non-pathogenic [13]. These commensal microbes play an important role in immune regulation, nutrition, and maintenance of host barriers against pathogens [14, 15]. It was reported that during diarrhea episodes (dysbiosis) in post-transplant patients, there is an increase in Proteobacteria and a decrease in Bacteroides, Ruminococcus, Coprococcus, and Dorea.
Although there are clinical trials offering information about microbiota composition in patients with diarrhea, there is not much information that links it to probiotic use after kidney transplantation.
The main objectives of this clinical trial are:
- To investigate if daily use of low dose probiotics is effective in alleviating symptoms of diarrhea as well as lowering pro-inflammatory and inflammatory biomarkers and increasing anti-inflammatory biomarkers in renal transplant recipients.
- To characterize microbiota in subjects with and without diarrhea and determine if there is any correlation between microbiota content and pro-inflammatory, inflammatory, and anti-inflammatory biomarkers.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Dietary Supplement: Placebo SupplementationSubjects 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. |
| Treatment | Active comparator | Dietary Supplement: Florajen Digestion SupplementationSubjects 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. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Florajen Digestion SupplementationSubjects 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. | Dietary supplement | Treatment |
| Placebo SupplementationSubjects 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. | Dietary supplement | Placebo |
Primary outcome
To investigate if daily use of low dose probiotics is effective in alleviating symptoms of diarrhea in post-transplant subjects
Time frame: 180 days
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.
Correlation of probiotic use with pro-inflammatory, inflammatory, and anti-inflammatory biomarkers
Time frame: 180 days
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
1 secondary outcome
To characterize microbiota in subjects with and without diarrhea
Time frame: 180 days
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Nov 2021.
- Background: PubMed 29920927Lee 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.
- Background: PubMed 17297402Ekberg 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.
- Background: PubMed 18295064Bunnapradist 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mark R Laftavi, MD principal investigator
State University of New York - Upstate Medical University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Florajen Digestion Supplementation in people with Diarrhea Caused by Drug and Dysbiosis, run by State University of New York - Upstate Medical University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 1 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To investigate if daily use of low dose probiotics is effective in alleviating symptoms of diarrhea in post-transplant subjects (time frame: 180 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05102461, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Nov 2021.