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| Name | Class |
|---|---|
| The Broad Foundation | OTHER |
| Brigham and Women's Hospital | OTHER |
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The human immune system is usually tolerant of the millions of beneficial commensal bacteria (the microbiome), which colonize the healthy intestinal tract. In contrast, patients with Inflammatory Bowel Disease (IBD) may play host to an imbalanced mix of such intestinal bacteria, which initiates abnormal immune responses in susceptible individuals. The resulting inflammation that occurs in the gastrointestinal tract damages the intestinal lining, leading to symptoms (such as intractable diarrhea, pain or weight loss), heightened cancer risk, other serious complications with substantial morbidity and even death. Current therapies for IBD focus on suppressing the excessive immune response to these bacteria, but have major side effects and do not address any role of the microbiome in disease development.
The investigators hypothesize that there is heightened intraluminal generation of pro-inflammatory factors by luminal "pathogenic" bacteria, such as extracellular nucleotides and purinergic derivatives, which trigger host immune cells. This results in loss of suppressive T regulatory cells with unrestrained immune cell deviation to pathogenic T helper cells that cause inflammatory responses. The investigators' proposal is that correcting the disease-provoking microbiome would beneficially improve gut microbial diversity, alter immune responses elicited in patients by such microbial products of pathogenic bacteria, and ultimately limit and suppress disease activity.
To test the hypothesis, the investigators propose to enroll patients with active Crohn's Disease, and introduce the microbiome of healthy and unrelated individuals to patient's intestinal tract, via fecal biotherapy (FBT) with all applicable safety measures. The investigators propose to comprehensively test the effects of FBT on the host microbiome, determine microbial production of inflammatory nucleotides and derivatives, which the investigators suggest might impact the host immune response and disease activity in patients with IBD.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Fecal Microbial Transplantation | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Fecal Microbial Transplantation | Biological |
|
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| Measure | Description | Time Frame |
|---|---|---|
| Safety of FMT in patients with Crohn's disease, as measured by number and nature of adverse events | 24 weeks | |
| Recipients' fecal microbial diversity after FMT, when compared to baseline | 12 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Recipients' fecal microbial diversity at 4 and 8 weeks after FMT, when compared to baseline | 8 weeks | |
| Mean change in Harvey Bradshaw Index (HBI) score | 12 weeks | |
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Inclusion Criteria (Patients):
Exclusion Criteria (Patients):
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| Name | Affiliation | Role |
|---|---|---|
| Alan C Moss, MD | Beth Israel Deaconess Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Beth Israel Deaconess Medical Center | Boston | Massachusetts | 02215 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 27542133 | Derived | Vaughn BP, Vatanen T, Allegretti JR, Bai A, Xavier RJ, Korzenik J, Gevers D, Ting A, Robson SC, Moss AC. Increased Intestinal Microbial Diversity Following Fecal Microbiota Transplant for Active Crohn's Disease. Inflamm Bowel Dis. 2016 Sep;22(9):2182-90. doi: 10.1097/MIB.0000000000000893. |
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| ID | Term |
|---|---|
| D003424 | Crohn Disease |
| ID | Term |
|---|---|
| D015212 | Inflammatory Bowel Diseases |
| D005759 | Gastroenteritis |
| D005767 | Gastrointestinal Diseases |
| D004066 | Digestive System Diseases |
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| ID | Term |
|---|---|
| D000069467 | Fecal Microbiota Transplantation |
| ID | Term |
|---|---|
| D001691 | Biological Therapy |
| D013812 | Therapeutics |
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| Percentage of patients in clinical remission (those with an HBI score at week 12 <5) |
| 12 weeks |
| Mean change in Short Inflammatory Bowel Disease Questionnaire (sIBDQ) score | 12 weeks |
| Percentage of patients in endoscopic remission (CDEIS score <3) | 12 weeks |
| Percentage of patients with mucosal healing (CDEIS score <1) | 12 weeks |
| Mean change in CRP levels | 12 weeks |
| Mean change in Crohn's Disease Endoscopic Index of Severity (CDEIS) score | 12 weeks |
| Tolerability score | 2 weeks |
| D007410 | Intestinal Diseases |