GMT: Gut Microbial Transplantation in Pediatric Inflammatory Bowel Diseases

• Sponsor: Spectrum Health Hospitals (Other)
• Overall Status: Completed
• CT.gov ID: NCT01560819
• Collaborator: (none)
• Enrollment: 20
• Location: 1
• Arm: 1
• Duration (Months): 15
• Patients Per Site Per Month: 1.3

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Inflammatory Bowel Disease (IBD)	Drug: Gut Microbial Transplantation	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 20 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Gut Microbial Transplantation in Pediatric Inflammatory Bowel Diseases
• Study Start Date: Mar 1, 2012
• Actual Primary Completion Date: Dec 1, 2012
• Actual Study Completion Date: Jun 1, 2013

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Clinical Response [4 weeks following GMT Treatment]

   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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 7 Years to 21 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

8. History of opportunistic infection (tuberculosis, Pneumocystis jirovecii or systemic fungal infections) in last one year or

9. Neutropenia: Absolute neutrophil count (ANC) <500

10. Major intra-abdominal surgery within 90 days prior to Day 1 of GMT

11. Administration of any investigational drug within 30 days prior to Day 1 of GMT.

12. 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:

2. Hepatitis A Immunoglobulin M (IgM) antibody

3. Hepatitis B antibody panel suggestive of infection (HBc IgM, HBs Ag, HBs Ab)

4. Hepatitis C antibody Level

5. Cytomegalovirus (CMV) IgM antibody

6. Ebstein Barr Virus (EBV) viral capsid antigen (VCA) IgM antibody

7. Syphilis Immunoglobulin G (IgG) Ab Screen

8. Human Immune Deficiency Virus (HIV) I & II enzyme-linked immunosorbent assay (ELISA) screen

9. 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

10. History of metabolic syndrome or gastric bypass surgery

11. 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

12. Antibiotic or probiotic use within 3 months before enrollment and for the duration of the donation

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

14. History of active malignancy or any cancer within the last 5 years (excluding basal cell carcinoma of the skin)

15. Family history of Creutzfeld-Jacob disease

16. Corneal or dural transplant

17. 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)

18. History of signs of sexually transmitted infections such as genital ulcerations, anogenital herpes, anogenital warts, cancroids or syphilitic lesions

19. Use of illicit drugs

20. Travel within the last 6 months to areas of the world where diarrheal illnesses are endemic

21. 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:

22. Oral thrush

23. Disseminated lymphadenopathy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Helen DeVos Children's Hospital of Spectrum Health Hospitals	Grand Rapids	Michigan	United States	49503

Sponsors and Collaborators

• Spectrum Health Hospitals

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Spectrum Health Hospitals
• ClinicalTrials.gov Identifier: NCT01560819
• Other Study ID Numbers: 2011-233
• First Posted: Mar 22, 2012
• Last Update Posted: Dec 30, 2013
• Last Verified: Dec 1, 2013

• Keywords provided by Spectrum Health Hospitals: ulcerative colitis, gut microbial transplantation
• Additional relevant MeSH terms: Intestinal Diseases; Inflammatory Bowel Diseases

Study Results

Participant Flow

Recruitment Details	An open-label, uncontrolled, single-center, prospective pilot study was conducted at Helen DeVos Children's Hospital's outpatient gastroenterology center. Participants were enrolled between April and December 2012. Each participant took part in the study for 6 weeks. The study was not advertised.
Pre-assignment Detail	Fifteen patients with ulcerative colitis (UC) were assessed for eligibility; all showed interest in the study. Ten participants met the eligibility criteria and the donors were identified by the participants.

Arm/Group Title	Study Participants	Donors
Arm/Group Description	Ten participants between the ages of 7 to 21 years with mild-to moderate UC (pediatric UC activity index [PUCAI] between 15 and 65) were enrolled in the study. PUCAI is a validated tool to measure disease activity in pediatric UC based on clinical symptoms: a score of <10 = remission; 10-34 = mild disease; 35-64 = moderate disease; 65-85 = severe disease. Participants had stable disease activity and medical treatment for UC for 2 months prior to enrollment. Participants' ongoing treatment for UC was not changed. None of the subjects had concurrent C difficile infection.	Healthy donors (>18 years of age) were chosen by the participants. Donors were required to complete a screening questionnaire, provide medical history, and undergo blood and stool tests.
Period Title: Overall Study
STARTED	10	10
COMPLETED	9	10
NOT COMPLETED	1	0

Baseline Characteristics

Arm/Group Title	Study Participants	Donors	Total
Arm/Group Description	Ten participants between the ages of 7 to 21 years with mild-to moderate UC (pediatric UC activity index [PUCAI] between 15 and 65) were enrolled in the study. PUCAI is a validated tool to measure disease activity in pediatric UC based on clinical symptoms: a score of <10 = remission; 10-34 = mild disease; 35-64 = moderate disease; 65-85 = severe disease. Participants had stable disease activity and medical treatment for UC for 2 months prior to enrollment. Participants' ongoing treatment for UC was not changed. None of the subjects had concurrent C difficile infection.	Healthy donors (>18 years of age) were chosen by participants. Donors were required to complete a screening questionnaire, provide medical history, and undergo blood and stool tests.	Total of all reporting groups
Overall Participants	10	10	20
Age, Customized (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	15.2 (4.4)	39.6 (12.7)	27.4 (15.6)
Sex: Female, Male (Count of Participants)
Female	4 40%	4 40%	8 40%
Male	6 60%	6 60%	12 60%
Disease Extent (Number) [Number]
Extensive	1 10%	0 0%	1 5%
Left-sided	1 10%	0 0%	1 5%
Pancolitis	6 60%	0 0%	6 30%
Proctitis	2 20%	0 0%	2 10%
Disease Activity before Treatment (Number) [Number]
0-9: Remission	0 0%	0 0%	0 0%
10-34: Mild Disease	3 30%	0 0%	3 15%
35-64: Moderate Disease	7 70%	0 0%	7 35%
65-85: Severe Disease	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Clinical Response
Description	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
Time Frame	4 weeks following GMT Treatment

Outcome Measure Data

Analysis Population Description

One participant showed intolerance to the treatment (immediate leaking of enema) and was not included in post-treatment disease activity evaluation.

Arm/Group Title	Study Participants
Arm/Group Description	Ten participants between the ages of 7 to 21 years with mild-to moderate ulcerative colitis (UC) (pediatric UC activity index [PUCAI] between 15 and 65) were enrolled in the study. PUCAI is a validated tool to measure disease activity in pediatric UC based on clinical symptoms: a score of <10 = remission; 10-34 = mild disease; 35-64 = moderate disease; 65-85 = severe disease. Participants had stable disease activity and medical treatment for UC for 2 months prior to enrollment. Participants' ongoing treatment for UC was not changed. None of the subjects had concurrent C difficile infection.
Measure Participants	9
Number [Participants]	9 90%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Study Participants
	Comments	A power calculation was not done for this pilot study. Changes in PUCAI post-treatment were compared with baseline using the Wilcoxon signed rank test. P value <0.05 was considered statistically significant.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.03
	Comments
	Method	Wilcoxon signed rank test
	Comments

Adverse Events

Time Frame	Adverse events (AEs) were recorded during and until 4 weeks after GMT using a symptom diary that participants completed. Common Terminology Criteria for Adverse Events and Toxicity Grading Guidance from Vaccine Clinical Trials (FDA, 2007) were used.
Adverse Event Reporting Description	AEs were collected for study participants, but not donors. Intensity of AEs was classified as mild, moderate, severe, or disabling. AEs were categorized as unrelated or possibly, probably, or definitely related to GMT. Data safety monitoring board was established to monitor AEs and review halting criteria after every 3 participants completed GMT.
Arm/Group Title	Study Participants
Arm/Group Description	Ten participants between the ages of 7 to 21 years with mild-to moderate UC (pediatric UC activity index [PUCAI] between 15 and 65) were enrolled in the study. Participants had stable disease activity and medical treatment for UC for 2 months prior to enrollment. Participants' ongoing treatment for UC was not changed. None of the subjects had concurrent C difficile infection.
All Cause Mortality
	Study Participants
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Study Participants
	Affected / at Risk (%)	# Events
Total	0/10 (0%)
Other (Not Including Serious) Adverse Events
	Study Participants
	Affected / at Risk (%)	# Events
Total	10/10 (100%)
Gastrointestinal disorders
Bloating/flatulance	9/10 (90%)	11
Abdominal pain/cramping	6/10 (60%)	11
Diarrhea	6/10 (60%)	9
Blood in stool	3/10 (30%)	5
General disorders
Fatigue	3/10 (30%)	3
Fever	2/10 (20%)	2

Limitations/Caveats

This short-term pilot study is limited by its small sample size; therefore, studies with a larger sample size and longer follow-up period will be required to determine true efficacy of GMT in patients with ulcerative colitis (UC).

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.