A Phase 1 interventional study of MICROBIOTA and PLACEBO in Crohn Disease, Pediatric Crohns Disease and Inflammatory Bowel Diseases, sponsored by McMaster Children's Hospital. Completed at 2 sites in Canada. Open to participants aged 3 Years to 17 Years. Per ClinicalTrials.gov, last updated 2023-10-19.
Sponsored by McMaster Children's Hospital · Phase 1, Interventional, and Treatment
The objective of this study is to assess the feasibility of a novel colonic and oral fecal microbiota transplantation protocol for the treatment of active pediatric Crohn's disease (CD). Specifically, we will test the hypothesis that a protocol of combination fecal microbiota colonoscopic infusion and oral microbiota capsules (OMC), using live fecal material from anonymous unrelated donors, can improve the disease activity of pediatric CD patients.
Several recent studies have assessed the role of fecal microbiota transplantation (FMT) in the treatment of inflammatory bowel disease (IBD). IBD is a chronic autoimmune gastrointestinal disorder that has been associated with disease-specific microbial signatures in the host. The vast majority of literature on the therapeutic role of FMT has assessed its role in the treatment of acute Clostridium difficile colitis, but its effectiveness at treating this disease condition suggests a central role of the microbiome in host immune tolerance.
A. Alterations in the IBD Microbiome Investigators have characterized specific alterations of the gut microbiota in ulcerative colitis and Crohn's disease, compared to healthy controls. Patients with active IBD may have a relative depletion in anaerobic microbes, such as Bacteroides vulgatus, Lachnospiraceae (p: Firmicutes), and an increase in Proteobacteria and Bacillus (p: Firmicutes). These microbial signatures of IBD have led to several hypotheses about the protective, and pathological roles of different resident intestinal bacterial species. Conte et al have suggested that B. vulgatus may have a protective role against colitis, downregulating inflammation. Other studies have suggested that dysbiosis in IBD leads to decreased production of key short-chain fatty acids, such as butyric acid metabolized by Faecalibacterium prausnitzii. Directly, butyric acid and other short-chain fatty acids are key substrates absorbed by colonocytes, and indirectly, butyrate may inhibit inflammatory processes in the intestinal mucosa by suppressing cytokines, like interleukin-8. These studies have attempted to define canonical "intestinal-microbial-immune axes," supporting the hypothesis that IBD may occur secondary to an altered microbiome in a genetically, immunologically susceptible host. This constant host-microbial cross-talk may thus be altered by the introduction of key bacterial species that are otherwise absent, or decreased as a consequence of active mucosal inflammation, in the IBD gut. While FMT would not provide targeted, species-specific inoculations, whole stool transplant would theoretically introduce a broad range of bacteria, including those that are theoretically "favorable" to the host.
B. The Pediatric Microbiome Pediatric IBD, and the pediatric microbiome, have several unique features that suggest microbial-based therapies could be particularly effective. Crohn's disease and ulcerative colitis typically have a much more aggressive course in the pediatric age group, suggesting that the pediatric IBD phenotype may have a pathophysiology that is distinct from adult-onset IBD. In pediatric IBD, the early age of onset makes the cumulative burden of medications, nutritional impairment, and surgery greater. Several standard IBD medication therapies have unique, age-specific toxicities in children. The overlap of pediatric chronic disease with critical periods of growth, bone accretion, and psychosocial development can make disease exacerbations disproportionately affect a child's long-term outcome. The pediatric microbiome itself has key differences. The shorter latency of disease may offer a unique window to reverse an underlying state of "dysbiosis." The pediatric microbiome may be more malleable than a fully defined adult microbiome, and the relatively immature immune system of children may be more influenced by FMT.
C. FMT for the Treatment of Pediatric IBD Four case series have been published for the treatment of pediatric ulcerative colitis (UC) and CD using FMT. Protocols varied between all studies, and three main routes of administration were used: serial enemas, serial enemas with supplementary colonoscopic administration, and nasogastric tube. The first published study, involved five enemas administered daily to 9 UC patients, ages 7-21. Outcomes included clinical improvement from baseline using Pediatric Ulcerative Colitis Activity Index (PUCAI) scores, at one-week, and one-month post-treatment. 6/9 patients maintained clinical response at their one-month follow-up assessment. In 2015, two case series of FMT for CD and UC patients were published. A single FMT infusion was administered via nasogastric tube (NGT) to 4 UC, and 9 CD patients. No clinical response was seen in UC through NGT administration. In contrast, remission was induced in 7/9 CD patients within 2-weeks post-treatment, with 5/9 maintaining remission at week 6 and week 12. The most recent pediatric case series from 2015 included a cohort of pediatric UC patients treated with oral 5-ASA monotherapy, who received a combination of serial FMT enemas and colonoscopic infusions. 3 patients were included; 100% went into clinical remission at week 2, sustained clinical remission at week 4, and had complete withdrawal of immunotherapy at time of publication. Within the limitations of this small case series, there was a correlation between the number of FMT administrations, and the duration of remission.
Two single-center pediatric case reports have recently been published showing marked clinical improvement in two patients with severe colitis. A 2015 case report describes a 4-month old female presenting with an early-onset colitis with UC-like phenotype. The patient was refractory to treatment with azathioprine and corticosteroids, and did not respond to further treatment with probiotics, a trial of amino-acid based formula, or infliximab. 2 serial FMT infusions with anonymous donor stool were administered via colonoscope, and a subsequent 5 infusions via nasoduodenal tube. These interventions led to clinical improvement, and complete resolution of histopathologic changes 6-months post FMT. A recent, 2016 case report describes an 11-year old female with corticosteroid-dependent UC who was unresponsive to treatment with 5-aminosalicylic acid and tacrolimus14. An initial FMT using her father's donor stool was performed via colonoscopy, and subsequent daily FMTs via fecal retention enema over the next 4 days, followed by 11 additional FMTs via retention enema every 2 to 4 weeks over 10 months. The patient remained in clinical remission at 40 weeks post final FMT, and showed complete endoscopic healing.
D. Clinical Observations from Published Pediatric IBD FMT Studies Despite promising results, major drawbacks to these four pediatric studies include small sample sizes and their open label study design. Studies of clinical response demand a blinded study protocol, particularly given that many patients who enrol in FMT studies are a self-selected group, who already believe in the therapeutic value of "natural" treatments. Further, inflammatory bowel disease has well-described associations between clinical symptoms, mucosal disease activity and underlying stressors; thus, patient bias may have a significant influence on self-reported PUCAI/PCDAI (Pediatric Crohn's Disease Activity Index) scores when measuring clinical response. In addition, it is also important to note that success of FMT for IBD reflected in the aforementioned studies may reflect a propensity for studies with positive results to be published and unreported, unsuccessful studies may exist.
1,992 studies on the registry are indexed under Crohn Disease; 478 are open to participants now.
This study's enrollment of 17 is below the median of 67 across 1,260 interventional studies indexed under Crohn Disease.
Browse Crohn Disease studies →McMaster Children's Hospital is the lead sponsor of 22 studies on the registry; 3 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Patients randomized to the INTERVENTION arm will receive a baseline fecal microbiota transplant (FMT) colonoscopic infusion at Week 0, followed by twice-weekly oral microbiota capsule (OMC) therapy for 6 weeks (including Week 0). (n = 30)
Biological: MICROBIOTA
Patients randomized to the CONTROL arm will receive a baseline normal saline (NS) colonoscopic infusion at Week 0, followed by twice-weekly dextrose-containing oral placebo capsule (OPC) therapy for 6 weeks (including Week 0). (n = 15)
Biological: PLACEBO
Fecal microbiota enema (RBX2660) infused via colonoscope x 1 + oral microbiota capsules (RBX7455) x 6 weeks. The fecal microbiota enema (RBX2660) prepared by Rebiotix has received Health Canada Clinical Trials Application (CTA), and U.S. Food and Drug Administration Investigational New Drug Application (IND) approval for clinical trials in patients with recurrent Clostridium difficile infection, and pediatric inflammatory bowel disease. The human-derived fecal oral microbiota capsule (RBX7455) has received U.S. Food and Drug Administration Investigational New Drug Application (IND) approval for clinical trials in patients with recurrent Clostridium difficile infection.
Also known as: RBX2660, RBX7455, Fecal microbiota transplant
Placebo enema (Normal Saline) infused via colonoscope x 1 + oral placebo capsules (dextrose-containing capsules) x 6 weeks. NOTE: Patients randomized to the control group will be given the option of receiving open-label treatment, with the intervention therapy, either: upon completion of the trial, or if they are removed from the trial due to disease exacerbation or other adverse event, at the discretion of their primary gastroenterologist.
Monthly Recruitment Rate
Assessment of recruitment rate (based on patients meeting all eligibility criteria who were approached for trial entry)
Time frame: 30 weeks
Dropout Rate Post Enrolment
Rate of patients leaving the trial (patient, or protocol directed exclusion) after enrolment
Time frame: 30 weeks
Rate of Patient Protocol Adherence
Rate of patients providing all required blood, stool and urine samples per protocol
Time frame: 30 weeks
Rate of Adverse Events
Rate of patients requiring hospitalization, or experiencing PCDAI increase ≥20 x 2 successive measures
Time frame: 30 weeks
Clinical: Improvement in Disease Symptoms
PCDAI decrease ≥15 from baseline: Week 6, Week 30
Time frame: Baseline, Week 6, Week 30
Clinical: Remission in Disease Symptoms
PCDAI ≤ 10: Week 6, Week 30
Time frame: Week 6, Week 30
Clinical: Improvement in Serum Inflammatory Markers
Decrease C-reactive protein from baseline: Week 6, Week 30
Time frame: Baseline, Week 6, Week 30
Clinical: Improvement in Mucosal Inflammatory Markers
Decrease fecal calprotectin from baseline: Week 6, Week 30
Time frame: Baseline, Week 6, Week 30
Clinical: Change in Urine Metabolomics
Change in urine metabolite profile from baseline: Week 6, Week 30
Time frame: Baseline, Week 6, Week 30
Clinical: Change in Fecal Microbiome
Change in fecal 16s rRNA + metagenomics profile baseline: Week 6, Week 30
Time frame: Baseline, Week 6, Week 30
Plan to share: Undecided
This study is completed, as verified in Oct 2023. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Studies of the drug tested here: RBX2660
McMaster Children's Hospital