Gut Microbial Transplantation in Pediatric Inflammatory Bowel Diseases

Inflammatory Bowel Disease (IBD) Clinical Trial

— GMT  

Official title:

Gut Microbial Transplantation in Pediatric Inflammatory Bowel Diseases

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01560819
• Other study ID #: 2011-233
• Status: Completed
• Phase: Phase 1
• Start date: March 2012
• Est. completion date: June 2013

Study information

• Verified date: May 2023
• Source: Spectrum Health Hospitals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: June 2013
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 7 Years to 21 Years

Eligibility

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

Related Conditions & MeSH terms

• Inflammatory Bowel Disease (IBD)
• Inflammatory Bowel Diseases
• Intestinal Diseases

Intervention

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.

Locations

Country	Name	City	State
United States	Helen DeVos Children's Hospital of Spectrum Health Hospitals	Grand Rapids	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
Spectrum Health Hospitals

Country where clinical trial is conducted

United States, 

References & Publications (1)

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):59 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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