Microbiome Treatment for Colitis
(FMT-ELIMINATE Trial)
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Diwakar Davar
Must be taking: Corticosteroids
Must not be taking: Biologics
Disqualifiers: Immunodeficiency, Immunosuppression, MDRO risk, others
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?Multiple retrospective studies suggest that the administration of corticosteroids to treat irAEs is safe, and does not compromise efficacy of ICI therapy in cancer patients. While \~67% of patients respond to corticosteroids, 33% of patients require biologic therapy such as TNFα inhibitors (e.g. infliximab), integrin α4β7 inhibitors (e.g. vedolizumab), or JAK/STAT inhibitors (e.g. tofactinib). This study aims to determine that distinct pathobionts govern the development of irCAE and IMC; and that the administration of hdFMT may reverse steroid-refractory irCAEs or IMC. The use of hdFMT has been shown to be effective in steroid and biologic (TNFα and/or integrin α₄β₇ inhibitor) refractory colitis in PD-1 and/or CTLA-4 ICI treated cancer patients in single-institution case series.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications. However, you must not have received certain biologic therapies before enrolling, and you should not be on other forms of immunosuppressive therapy besides steroids or biologics within 7 days prior to the trial.
What data supports the effectiveness of the treatment MTP-101-C for colitis?
Research shows that fecal microbiota transplantation (FMT), a treatment similar to MTP-101-C, has been effective in improving symptoms in patients with immune-mediated colitis and ulcerative colitis. In one study, 83% of patients with severe colitis symptoms improved after FMT, and 92% achieved clinical remission, suggesting that altering gut bacteria can help manage colitis.
12345Is the microbiome treatment for colitis safe for humans?
Fecal microbiota transplant (FMT), a type of microbiome treatment, has been used safely in treating conditions like ulcerative colitis and Clostridium difficile infection, but more studies are needed to fully understand the risks and best practices for its use in inflammatory bowel diseases.
16789How is the treatment MTP-101-C for colitis different from other treatments?
MTP-101-C is unique because it focuses on altering the gut microbiome (the community of bacteria in the intestines) to treat colitis, which is different from traditional treatments that often target inflammation directly. This approach is similar to fecal microbiota transplantation, which has shown promise in inducing remission in colitis by changing the bacterial composition in the gut.
1011121314Eligibility Criteria
This trial is for individuals with immune-related skin issues like eczema or colitis that haven't improved after steroid treatment. Participants should have these conditions due to cancer immunotherapy and must not respond well to other biologic treatments.Inclusion Criteria
Participant provides written informed consent for the trial
Willingness to use contraception for the duration of trial participation
Willingness to undergo correlative blood and stool sampling
+15 more
Exclusion Criteria
Patients at high risk of MDRO colonization
I have experienced multiple immune-related side effects.
I have not received any live vaccines in the last 30 days.
+6 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
1 week
1 visit (in-person)
Treatment
Participants receive MTP-101-C (encapsulated fecal microbiota) for 28 days, with steroids tapered rapidly
4 weeks
Weekly visits (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment, including endpoint assessments and biospecimen collection
2 weeks
2 visits (in-person)
Long-term Follow-up
Participants are monitored for resolution of symptoms and adverse events up to 2 months
4 weeks
Participant Groups
The study tests MTP-101-C, a healthy-donor microbiome therapy, on patients who didn't get better from steroids or biologics for their skin problems or colitis caused by cancer treatments.
2Treatment groups
Experimental Treatment
Group I: MTP-101-C (Cohort 2: Steroid R/R biologic-naive colitis)Experimental Treatment1 Intervention
Patients given MTP-101-C (encapsulated fecal microbiota, containing \~5 x 1011 bacteria derived from healthy donors).
Dosing:
5 capsules/day (Day 1); 2 capsules/day (D2-D28)
Group II: MTP-101-C (Cohort 1: Steroid R/R biologic-naive dermatitis)Experimental Treatment1 Intervention
Patients given MTP-101-C (encapsulated fecal microbiota, containing \~5 x 1011 bacteria derived from healthy donors).
Dosing:
5 capsules/day (Day 1); 2 capsules/day (D2-D28)
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
UPMC Hillman Cancer CenterPittsburgh, PA
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Who Is Running the Clinical Trial?
Diwakar DavarLead Sponsor
Stanley Marks Fund for Cancer ResearchCollaborator
Cures Within ReachCollaborator
References
Long-term efficacy and safety of monotherapy with a single fresh fecal microbiota transplant for recurrent active ulcerative colitis: a prospective randomized pilot study. [2021]To assess the long-term safety and efficacy of monotherapy with a single fresh fecal microbiota transplant (FMT) for recurrent ulcerative colitis (UC).
Microbiome alteration via fecal microbiota transplantation is effective for refractory immune checkpoint inhibitor-induced colitis. [2023]Immune checkpoint inhibitors (ICIs) target advanced malignancies with high efficacy but also predispose patients to immune-related adverse events like immune-mediated colitis (IMC). Given the association between gut bacteria with response to ICI therapy and subsequent IMC, fecal microbiota transplantation (FMT) represents a feasible way to manipulate microbial composition in patients, with a potential benefit for IMC. Here, we present a large case series of 12 patients with refractory IMC who underwent FMT from healthy donors as salvage therapy. All 12 patients had grade 3 or 4 ICI-related diarrhea or colitis that failed to respond to standard first-line (corticosteroids) and second-line immunosuppression (infliximab or vedolizumab). Ten patients (83%) achieved symptom improvement after FMT, and three patients (25%) required repeat FMT, two of whom had no subsequent response. At the end of the study, 92% achieved IMC clinical remission. 16S rRNA sequencing of patient stool samples revealed that compositional differences between FMT donors and patients with IMC before FMT were associated with a complete response after FMT. Comparison of pre- and post-FMT stool samples in patients with complete responses showed significant increases in alpha diversity and increases in the abundances of Collinsella and Bifidobacterium, which were depleted in FMT responders before FMT. Histologically evaluable complete response patients also had decreases in select immune cells , including CD8+ T cells, in the colon after FMT when compared with non-complete response patients (n = 4). This study validates FMT as an effective treatment strategy for IMC and gives insights into the microbial signatures that may play a critical role in FMT response.
Fecal microbiota transplantation induces remission of infantile allergic colitis through gut microbiota re-establishment. [2019]To investigate the impact of fecal microbiota transplantation (FMT) treatment on allergic colitis (AC) and gut microbiota (GM).
Microbial Butyrate Synthesis Indicates Therapeutic Efficacy of Azathioprine in IBD Patients. [2021]The microbial ecosystem seems to be an important player for therapeutic intervenption in inflammatory bowel disease [IBD]. We assessed longitudinal microbiome changes in IBD patients undergoing therapy with either azathioprine [AZA] or anti-tumour necrosis factor [anti-TNF] antibodies. We predicted the metabolic microbial community exchange and linked it to clinical outcome.
Microbiome-Based Biomarkers for IBD. [2021]Crohn disease and ulcerative colitis are complex immune-mediated diseases that are characterized by a heterogeneity in presentation and clinical course. Although various clinical covariates predict adverse outcomes in these patients, they are insufficiently informative. The gut microbiome likely plays a central role in the pathogenesis of these diseases. Consequently, microbiome-based biomarkers may play an important role in risk stratification and disease prediction. Initial cross-sectional studies showed a reduced gut microbial diversity in patients with Crohn disease or ulcerative colitis, a depletion of phyla with anti-inflammatory effects such as those belonging to Firmicutes, and an increased abundance of potentially pathogenic bacteria in specific disease phenotypes. Subsequent studies longitudinally tracking microbial changes and clinical outcomes have shown dynamic changes correlating with or predictive of disease activity and resistance to therapy. The development of multicenter cohorts using harmonized protocols is essential to robustly validate these biomarkers and facilitate the integration of their evaluation into clinical practice. .
The Efficacy and Safety of Mesalamine and Probiotics in Mild-to-Moderate Ulcerative Colitis: A Systematic Review and Meta-Analysis. [2022]To evaluate the efficacy and safety of mesalamine in conjunction with probiotics for ulcerative colitis.
Microbial-Based and Microbial-Targeted Therapies for Inflammatory Bowel Diseases. [2023]Inflammatory bowel diseases (IBD), including Crohn's disease, ulcerative colitis, and pouchitis, are chronic, relapsing intestinal inflammatory disorders mediated by dysregulated immune responses to resident microbiota. Current standard therapies that block immune activation with oral immunosuppressives or biologic agents are generally effective, but each therapy induces a sustained remission in only a minority of patients. Furthermore, these approaches can have severe adverse events. Recent compelling evidence of a role of unbalanced microbiota (dysbiosis) driving immune dysfunction and inflammation in IBD supports the therapeutic rationale for manipulating the dysbiotic microbiota. Traditional approaches using currently available antibiotics, probiotics, prebiotics, and synbiotics have not produced optimal results, but promising outcomes with fecal microbiota transplant provide a proof of principle for targeting the resident microbiota. Rationally designed oral biotherapeutic products (LBPs) composed of mixtures of protective commensal bacterial strains demonstrate impressive preclinical results. Resident microbial-based and microbial-targeted therapies are currently being studied with increasing intensity for IBD primary therapy with favorable early results. This review presents current evidence and therapeutic mechanisms of microbiota modulation, emphasizing clinical studies, and outlines prospects for future IBD treatment using new approaches, such as LBPs, bacteriophages, bacterial function-editing substrates, and engineered bacteria. We believe that the optimal clinical use of microbial manipulation may be as adjuvants to immunosuppressive for accelerated and improved induction of deep remission and as potential safer solo approaches to sustained remission using personalized regimens based on an individual patient's microbial profile.
Efficacy of fecal microbiota therapy in steroid dependent ulcerative colitis: a real world intention-to-treat analysis. [2021]Four high-quality randomized controlled trials have proven the efficacy of fecal microbiota transplantation (FMT) in active ulcerative colitis (UC). We assessed the efficacy of FMT in a real-world setting involving steroid-dependent patients with UC.
Fecal microbiota transplant - a new frontier in inflammatory bowel disease. [2023]Inflammatory bowel disease (IBD) is a chronic multifactorial disease that affects the gastrointestinal tract and results from an aberrant immune response toward luminal antigens in genetically susceptible people. Most of the current therapies for IBD focus on the management of the inflammation by using corticosteroids, immune modulators, and more recently, monoclonal antibodies (biological therapy). Although these therapies provide benefit in most cases, there are still a significant number of patients who do not respond or become refractory over time, suggesting the need for alternative therapeutic options. In the last decade, it has been recognized that "dysbiosis," an imbalanced gut microbiota, is a key element in IBD suggesting microbiome-based therapies as an attractive approach. Recently, fecal microbiota transplant (FMT) has been successfully used for the treatment of Clostridium difficile infection, and it is now under investigation for the treatment of IBD. Clinical trials data are still poor but strongly support a future introduction of FMT in therapy to manage IBD microbiome. More studies are needed to assess the optimal route of administration and the frequency of FMT, the best matched donor for each patient as well as the risks associated with FMT in IBD.
Fecal microbiota transplantation for refractory immune checkpoint inhibitor-associated colitis. [2022]We report the first case series of immune checkpoint inhibitors (ICI)-associated colitis successfully treated with fecal microbiota transplantation, with reconstitution of the gut microbiome and a relative increase in the proportion of regulatory T-cells within the colonic mucosa. These preliminary data provide evidence that modulation of the gut microbiome may abrogate ICI-associated colitis.
Specific Bacteria and Metabolites Associated With Response to Fecal Microbiota Transplantation in Patients With Ulcerative Colitis. [2019]Fecal microbiota transplantation (FMT) can induce remission in patients with ulcerative colitis (UC). In a randomized controlled trial of FMT in patients with active UC, we aimed to identify bacterial taxonomic and functional factors associated with response to therapy.
The Gut Microbiome as a Target for IBD Treatment: Are We There Yet? [2020]This review aims to highlight recent research on the gut microbiome in IBD and the application of microbiome-modulating therapies for the treatment of IBD including the use of the microbiome as an indicator for disease severity and treatment response.
An altered composition of the microbiome in microscopic colitis is driven towards the composition in healthy controls by treatment with budesonide. [2020]Background and aim: Microscopic colitis (MC) is an inflammatory disease of the bowel, hypothetically induced by an immunologic response to a luminal microbial agent. We aimed to characterize the microbiome composition in MC and subtypes collagenous colitis (CC) and lymphocytic colitis (LC) and to identify a possible microbial effect of treatment. Method: Stool samples were collected from MC patients prior to treatment, at 8 weeks (during treatment) and at 16 weeks (after treatment), and from healthy controls, not receiving treatment, at matched time-points. Microbiome composition was analyzed by sequencing of the 16S and 18S genes. Differences between patients and controls were analyzed by Shannon's diversity index (mean, standard deviation (SD)) and principal coordinate analysis (PCoA) complemented with a permanova test of UniFrac distances. Results: Ten LC patients, 10 CC patients and 10 controls were included. By PCoA, the bacterial composition in MC patients differed from controls at baseline (p = .02), but not during and after treatment (p = .09 and p = .33, respectively). At baseline, bacterial diversity was lower in MC patients compared to controls (2.5, SD: 0.5 vs 3.5, SD: 0.3, p < .05). Diversity in MC patients increased during (3.0, SD: 0.6) and after treatment and (2.9, SD: 0.5) compared with baseline (p < .01). Eukaryotes were detected in fewer samples from MC patients compared with controls (11/20 (55%) vs. 9/10 (90%), p = .06) with no effect of treatment. Conclusion: Microbiome composition is altered in MC patients. During and after treatment with budesonide the microbiome composition in MC patients was driven towards the composition in healthy controls.
Composition and diverse differences of intestinal microbiota in ulcerative colitis patients. [2022]To explore the composition of the intestinal microbiota in ulcerative colitis (UC) patients and to identify differences in the microbiota between patients with active disease and those in remission.