Gut Microbial Transplantation in Pediatric Inflammatory Bowel Diseases (GMT)

Inflammatory bowel disease (IBD) is a chronic, debilitating, relapsing inflammatory disorder affecting the gastrointestinal tract which does not have a medical cure. IBD consists of 2 different forms: Crohn's Disease (CD) and Ulcerative Colitis (UC). In the last 2 decades, Gut Microbial Transplantation (GMT), also known as fecal transplantation, has been used as a treatment option for Clostridium difficile colitis and UC. The literature supports strong evidence for the plausibility of using GMT for patients with IBD associated colitis, especially for patients with UC.

This research will be conducted in the Helen DeVos Children's Hospital (HDVCH) Pediatric gastrointestinal outpatient clinic. A pilot study of ten patients will be conducted to evaluate if GMT improves clinical symptoms in patients with IBD. Patients with IBD colitis (UC and CD with colonic involvement only) will be approached for GMT as a treatment option for their disease. Each subject will undergo 5 sessions (1 session/day, and not necessarily on consecutive days) of GMT within a period of 10 days. Post treatment evaluation will be done at their regularly scheduled clinic follow up.

Healthy donors >18 years of age will be chosen by the family, inclusive of immediate family members and friends. Donors will be required to complete a screening questionnaire, provide medical history, and undergo blood and stool tests.

Study Overview

• Status: Completed
• Conditions: Inflammatory Bowel Disease (IBD)
• Intervention / Treatment: Drug: Gut Microbial Transplantation

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Grand Rapids, Michigan, United States, 49503
      • Helen DeVos Children's Hospital of Spectrum Health Hospitals

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 years to 21 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Participant Inclusion Criteria:

1. Children ages >7 and ≤21 years of age with established diagnosis of Inflammatory Bowel Disease (IBD) colitis (patient with ulcerative colitis (UC) or patients with crohn's disease (CD) with colonic involvement only)
2. Have clinical disease (mild to moderate disease: 10≤ Pediatric Ulcerative Colitis Activity Index (PUCAI) <65)
3. Have stable disease activity and therapy for two months prior to Gut Microbial Transplantation (GMT) procedure.

Participant Exclusion Criteria:

1. Fulminant colitis
2. Indication or scheduled for surgery
3. Pregnancy
4. Use of probiotic supplements during the study period (subjects who have stopped use of probiotic supplements will be eligible as long as they stop taking it 2 weeks prior to Day 1 of GMT)
5. anemia (hemoglobin < 6.0 g/dL) in last one month
6. Graft versus host disease (GVHD)

7. Severely immunocompromised - defined as

   1. History of opportunistic infection (tuberculosis, Pneumocystis jirovecii or systemic fungal infections) in last one year or
   2. Neutropenia: Absolute neutrophil count (ANC) <500
8. Major intra-abdominal surgery within 90 days prior to Day 1 of GMT
9. Administration of any investigational drug within 30 days prior to Day 1 of GMT.
10. Have received infliximab or other tumor necrosis factor (TNF) inhibitors within 2 months prior to Day 1 of GMT or are expected to receive such therapy within 1 month post final GMT.

Donor Inclusion Criteria

1. Based on patient's and parents'/guardian's decision
2. Will be chosen from immediate adult (≥18 years) family members or close friends
3. Should have negative or normal results on screening tests (as explained in donor exclusion criteria below)

Donor Exclusion Criteria (adopted from guidelines provided by American Association of Blood Bank Donor History Questionnaire and American Gastroenterological Association)

1. Positive or abnormal screening test to include:

   1. Hepatitis A Immunoglobulin M (IgM) antibody
   2. Hepatitis B antibody panel suggestive of infection (HBc IgM, HBs Ag, HBs Ab)
   3. Hepatitis C antibody Level
   4. Cytomegalovirus (CMV) IgM antibody
   5. Ebstein Barr Virus (EBV) viral capsid antigen (VCA) IgM antibody
   6. Syphilis Immunoglobulin G (IgG) Ab Screen
   7. Human Immune Deficiency Virus (HIV) I & II enzyme-linked immunosorbent assay (ELISA) screen
   8. Stool i) Fungal smear ii) Stool cultures to exclude Salmonella, Shigella, Escherichia Coli, Campylobacter, Yersinia, Vibrio, Listeria iii) Clostridium difficile toxin assay iv) Ova and parasite screen for Giardia and Cryptosporidium
2. History of metabolic syndrome or gastric bypass surgery
3. History of GI conditions: IBD, irritable bowel syndrome, chronic abdominal pain, GI Malignancy, blood in stool or diarrhea in the last 4 weeks before enrollment
4. Antibiotic or probiotic use within 3 months before enrollment and for the duration of the donation

5. Positive response on screening questionnaire to any of the following:

   1. History of active malignancy or any cancer within the last 5 years (excluding basal cell carcinoma of the skin)
   2. Family history of Creutzfeld-Jacob disease
   3. Corneal or dural transplant
   4. History of high risk sexual behavior (e.g. sexual contact with HIV/acquired immune deficiency syndrome (AIDS) positive, hepatitis positive partner, men who have sex with men, sex for drugs or money)
   5. History of signs of sexually transmitted infections such as genital ulcerations, anogenital herpes, anogenital warts, cancroids or syphilitic lesions
   6. Use of illicit drugs
   7. Travel within the last 6 months to areas of the world where diarrheal illnesses are endemic
   8. History or signs of immunosuppression i) History of any immunosuppressant medication(s) within the last 6 months or history of opportunistic infection(s) in past 1 year ii) Signs of immunosuppression such as:
   1. Oral thrush
   2. Disseminated lymphadenopathy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Study Participants; Participants did not receive any bowel preparation before Gut Microbial Transplantation (GMT). Audio-visual aids were used to help reduce participants' anxiety about GMT.

Drug: Gut Microbial Transplantation; Each participant received Gut Microbial Transplantation (GMT) as retention enema over a period of 1 hour (60mL enema every 15 minutes) daily for 5 days. Although 240mL of GMT solution was prepared for each participant, the final administered dose was dependent on the subject's comfort and willingness to proceed with the next enema, which was assessed after each enema infusion. Subjects were monitored for 30 minutes after GMT for any immediate adverse events and discharged.; Other Names: GMT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Response	Clinical response (i.e. improvement in Pediatric Ulcerative Colitis Activity Index (PUCAI) score by greater than or equal to 15 points from baseline) at 4 weeks following GMT treatment	4 weeks following GMT Treatment

Collaborators and Investigators

• Sponsor: Spectrum Health Hospitals
• Investigators: Principal Investigator: Sachin Kunde, MD, MPH, Helen DeVos Children's Hospital of Spectrum Health Hospitals

Publications and helpful links

General Publications

• Kunde S, Pham A, Bonczyk S, Crumb T, Duba M, Conrad H Jr, Cloney D, Kugathasan S. Safety, tolerability, and clinical response after fecal transplantation in children and young adults with ulcerative colitis. J Pediatr Gastroenterol Nutr. 2013 Jun;56(6):597-601. doi: 10.1097/MPG.0b013e318292fa0d.

Study record dates

Study Major Dates

• Study Start: March 1, 2012
• Primary Completion (Actual): December 1, 2012
• Study Completion (Actual): June 1, 2013

Study Registration Dates

• First Submitted: March 20, 2012
• First Submitted That Met QC Criteria: March 21, 2012
• First Posted (Estimated): March 22, 2012

Study Record Updates

• Last Update Posted (Estimated): June 2, 2023
• Last Update Submitted That Met QC Criteria: May 31, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: ulcerative colitis, gut microbial transplantation
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Inflammatory Bowel Diseases; Intestinal Diseases
• Other Study ID Numbers: 2011-233