Faecal Microbiota Transplantation in Patients With Microscopic Colitis

Microscopic Colitis Clinical Trial

Official title:

Faecal Microbiota Transplantation in Patients With Microscopic Colitis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03275467
• Other study ID #: 2017/072
• Status: Completed
• Phase: N/A
• Start date: June 1, 2017
• Est. completion date: October 31, 2019

Study information

• Verified date: February 2020
• Source: Örebro University, Sweden
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Microscopic colitis (MC) is a disease with chronic inflammation of the colon that is mostly diagnosed in middle-aged or elderly women. Patients suffer from chronic watery diarrhoea, abdominal pain and weight loss. The aetiology of MC is still unknown but it is hypothesized that MC is caused by a deregulated immune response to a luminal agent in predisposed individuals, and an important role of the intestinal microbiota is suggested.

In the current proof-of-concept study, the effect of faecal microbiota transfer (FMT) in 10 MC patients will be evaluated. FMT consists in the infusion of suspended stool from a healthy donor into the intestine of a patient with the aim to restore a disturbed intestinal microbiota.

Description:

This will be an intervention pilot study with a 12-week and an optional 6-months follow-up period. It will be investigated if the infusion of suspended stool from healthy donors improves the symptoms of MC patients by restoring their disturbed intestinal microbiota. This procedure is known as faecal microbiota transplantation (FMT).

MC patients (n=10) will be randomised to receive FMT using stool from one of two healthy donors.

At baseline, blood samples and mucosal biopsies will be obtained from the descending colon. In addition, faecal samples will be collected and patients will complete symptom questionnaires. The first FMT will be administered by colonoscopy, FMT 2-3 by enemas. Faecal samples will be collected and questionnaires will be completed at different time points during the study. The patients will be followed-up at 6 weeks, 8 weeks, 12 weeks and 6 months after receiving FMT 1, however, the follow-up after 6 months will be optional. Additional biopsies from the descending colon and blood samples will be collected 6 weeks after the first FMT.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: October 31, 2019
• Est. primary completion date: June 5, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion criteria for patients:

1. Signed informed consent

2. Active MC diagnosis, defined as >3 stools a day from which at least one should be watery

3. Willingness to stop budesonide treatment during participation in the trial

4. Age: 18-70 years

Exclusion criteria for patients

1. Previous complicated gastrointestinal surgery

2. Malignant disease except non-melanoma skin cancer

3. Dementia, severe depression, major psychiatric disorder, or other incapacity for adequate cooperation

4. C. difficile or other current gastroenteritis

5. Females who are pregnant or breast-feeding

6. Severe endometriosis

7. Antimicrobial treatment 4 weeks prior to first screening visit

8. Antimicrobial prophylaxis (eg. acne, urinary tract infection)

9. Regular consumption of probiotic products 4 weeks prior to randomization

10. Recently diagnosed lactose intolerance (less than 6 months prior to first screening visit)

11. Recently diagnosed coeliac disease (less than 6 months prior to first screening visit)

12. Regular intake of NSAIDs (non steroidal anti-inflammatory drugs)

13. Abuse of alcohol or drugs

14. Any clinically significant disease/condition which in the investigator's opinion could interfere with the results of the trial

Inclusion criteria for donors

1. Signed informed consent

2. High-butyrate producing microbiota in faecal samples

3. Age: 18-65 years

Exclusion criteria for donors

1. Known organic gastrointestinal disease (e.g. IBD, IBS, chronic diarrhoea or constipation)

2. First degree relative with IBD

3. History of or present gastrointestinal malignancy or polyposis

4. Recent (gastrointestinal) infection (within last 6 months)

5. History of major gastrointestinal surgery (e.g. gastric bypass)

6. Eosinophilic disorders of the gastrointestinal tract

7. Current communicable disease (e.g. upper respiratory tract infection)

8. Malignant disease and/or patients who are receiving systemic anti-neoplastic agents

9. Psychiatric diseases (e.g. dementia, depression, schizophrenia, autism, Asperger Syndrome) or other incapacity for adequate cooperation

10. Chronic neurological/neurodegenerative diseases (e.g. Parkinson's disease, multiple sclerosis)

11. Autoimmune disease and/or patients receiving immunosuppressive medications

12. Major relevant allergies (e.g. food allergy, multiple allergies)

13. Chronic pain syndromes (e.g. fibromyalgia)

14. Chronic fatigue syndrome

15. HIV, hepatitis A, B, C or known exposure within the recent 12 months

16. Obesity (BMI>30) or metabolic syndrome

17. Antimicrobial treatment or prophylaxis within the last 3 months

18. Other chronic use of drugs that may affect the microbiome, e.g. proton pump inhibitors

19. First degree relative with cardiovascular thrombosis before 50 years of age

20. Females who are pregnant or breast-feeding

21. Known clinically significant abnormal laboratory values

22. Participation in high-risk sexual behaviours

23. Abuse of alcohol or drugs

24. Tattoo or body piercing within the last 6 months

25. Travelling in countries with low hygiene or high infection risk for endemic diarrhoea within the last 6 months

26. Positive stool testing for C. difficile, ova and parasites (e.g. Cyclospora, Isospora, Cryptosporidium), enteric pathogens (e.g. enterohaemorrhagic E. coli, Salmonella, Shigella, Yersinia, Campylobacter, Giarda antigen, amoebas)

27. Positive stool testing for multiresistant bacteria (e.g. extended-spectrum beta- lactamase (ESBL) producing organisms, multi-resistant Gram-negative bacilli (MRGN) 3 and 4, vancomycin-resistant enterococci (VRE) or methicillin-resistant Staphylococcus aureus (MRSA))

28. Calprotectin > 50 µg/g of faeces

29. Positive blood testing for HIV, Hepatitis A, B, C, syphilis, Human T-lymphotropic virus (HTLV), cytomegalovirus (CMV) and Epstein Barr Virus (EBV)

30. Any clinically significant disease/condition which in the investigator's opinion could interfere with the results of the trial

Related Conditions & MeSH terms

• Colitis
• Colitis, Microscopic
• Microscopic Colitis

Intervention

Other:
• Faecal microbiota transfer (FMT)
Suspended stool from a healthy donor

Locations

Country	Name	City	State
Sweden	University Hospital Örebro	Örebro	Örebro County

Sponsors (2)

Lead Sponsor	Collaborator
Örebro University, Sweden	Region Örebro County

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Changes in inflammation markers in faecal samples such as faecal calprotectin		6 weeks, 8 weeks, 12 weeks, 6 months
Other	Changes in metabolite profile in faecal samples and blood		faecal: 6 weeks, 8 weeks, 12 weeks, 6 months; blood: 6 weeks
Other	Changes in gene expression in mucosal biopsies		6 weeks
Other	Changes in barrier function markers in colonic biopsies		6 weeks
Other	Changes in gene expression of butyrate transporters in colonic biopsies		6 weeks
Other	Changes in markers of inflammation and intestinal barrier function in blood		6 weeks
Other	Changes in plasma levels of cardiovascular disease markers and platelet responsiveness and aggregation		6 weeks
Primary	Proportion of MC patients in remission six weeks after the first FMT.	Remission is defined as <3 stools per day and a mean of less than one watery stool per day.	6 weeks
Secondary	Changes in general health and symptom questionnaire scores	SHS	6 weeks, 8 weeks, 12 weeks, 6 months
Secondary	Changes in general health questionnaire scores	SF-36	6 weeks, 8 weeks, 12 weeks, 6 months
Secondary	Changes in quality of life questionnaire scores	EG-5D-5L	6 weeks, 8 weeks, 12 weeks, 6 months
Secondary	Changes in gastrointestinal symptom questionnaire scores	GSRS	6 weeks, 8 weeks, 12 weeks, 6 months
Secondary	Changes in hospital and anxiety depression scores	HADS	6 weeks, 8 weeks, 12 weeks, 6 months
Secondary	Changes in number and form of bowel movements	1-week-diaries	6 weeks, 8 weeks, 12 weeks, 6 months
Secondary	Changes in faecal and mucosal microbiota composition	16S rRNA-based next generation sequencing	faecal: 6 weeks, 8 weeks, 12 weeks, 6 months; mucosal: 6 weeks
Secondary	Changes in lymphocyte infiltration	Immunohistochemistry and flow cytometry	6 weeks
Secondary	Changes in subepithelial collagen layer	Immunohistochemistry	6 weeks
Secondary	Changes in immune cell composition of colonic biopsies	Immunohistochemistry and flow cytometry	6 weeks