Transplantation of Microbes for Treatment of Metabolic Syndrome & NAFLD

NCT02496390 | Completed Phase 1 DMC

• 1 other identifier: IDFMT - 001
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

Non-alcoholic fatty liver disease (NAFLD) occurs when excess fat is deposited in the liver. Almost all patients also have obesity and insulin resistance (the inability of the body to effectively use insulin). Obesity and NAFLD are intricately intertwined and are increasing in incidence. While weight loss is the most effective therapy for NAFLD, the investigators' efforts are failing and in the next generation it will become the most common cause of liver failure in Canada. Recently, researchers have focused on the potential use of altering the composition of bacteria in the gut (microbiome) to alter absorption of energy from food, deposition of fat and resistance to insulin. This study will determine if transplantation of bacteria from the stool of a healthy volunteer into an individual with metabolic syndrome and NAFLD (i.e. fecal microbiota transplant/FMT) can alter insulin resistance and reduce the amount of fat deposited in the liver. FMT is being studied to treat several clinical conditions and is now standard of care for the treatment of refractory Clostridium difficile infection. Investigators are proposing a randomized controlled pilot study of FMT in 21 patients to determine the feasibility and to inform us of changes needed for a larger study.

Conditions

Diabetes Mellitus; Non-alcoholic Fatty Liver Disease

Keywords

Fecal Microbial Transplantation; Gut microbiome; Metabolic disorders; Obesity

Outcome Measures

Primary Outcomes (1)

• Improvement in Homeostasis model assessment [HOMA] score.

  6 weeks

Secondary Outcomes (5)

• Fat reduction

  6 months

• Reducing body fat

  6 months

• Gut permeability

  6 months

• Microbiome modulation

  6 months

• Modulation of lipid and hormone metabolism

  6 months

Study Arms (2)

Autologous

PLACEBO COMPARATOR

Patients will be randomized to receive a fecal transplant using their own microbes/Feces (autologous - 9 patients). Dosage - approx 100ml fecal sample, one time, procedure duration \~1hr

Biological: Autologous

Allogenic

ACTIVE COMPARATOR

Patients will be randomized to receive a fecal transplant of feces/microbiome from the healthy donor (allogeneic - 12 patients). Dosage - approx 100ml fecal sample, one time, procedure duration \~1hr

Biological: Allogeneic

Interventions

Autologous BIOLOGICAL

Patients will have their normal microbiome reduced using an oral preparation (pico-salax) as used for routine colonic preparation for colonoscopy. • Administration of the FMT will be via a nasoduodenal tube inserted at the time of gastroscopy. Dosage - approx 100ml previously frozen fecal sample obtained from the patient prior to colonic preparation.

Also known as: Autologous fecal infusions

Autologous

Allogeneic BIOLOGICAL

Patients will have their normal microbiome reduced using an oral preparation (pico-salax) as used for routine colonic preparation for colonoscopy. • Administration of the FMT will be via a nasoduodenal tube inserted at the time of gastroscopy. Dosage - approx 100ml previously frozen fecal sample obtained from a lean donor prior to colonic preparation.

Also known as: Fecal Microbial Transplantation

Allogenic

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Attendance at the gastroenterology/hepatology clinic with a diagnosis of NAFLD as well as metabolic syndrome.
• Ability to provide informed Consent.

You may not qualify if:

• Type 1 or 2 Diabetes requiring ongoing hypoglycemic medications.
• Inability to attend follow-up visits.
• Inability to provide informed written consent.
• Ongoing use of antibiotics or probiotics.
• Previous or planned bariatric surgery.
• Presence of a chronic intestinal disease e.g. Celiac, malabsorption, Colonic tumor.
• Immunosuppression from transplantation, HIV, Cancer chemotherapy or ongoing use of any immunosupressive agents.
• Pregnant women
• Any contra-indications for MRI as listed below: a. Previous brain surgery (using the language outlined in the Health Sciences Research Ethics Board \[HSREB\] Guideline, section 2-G-004) Pacemaker, Cerebral aneurism clips, neurostimulator, Metallic heart valves, Intra Uterine Devices \[IUD\], Joint replacement, Metal plates Bone or joint pins, Venacava filters, Embolization coils, Cochlear implants, Greenfield Filter, Seizures, Claustrophobia, Bullet/gunshot wound, Non-removable prosthesis, Non-removable artificial limbs, Surgical clips, Metal screws or pins, Shrapnel/metallic fragments, Harrington rod, Insulin pump, Ever had metal removed from in or around the eye, Ever been a metal worker (i.e. welder, machinist), Non-removable hearing aids, Bird nest or Gianturco filter, Metal braces, Severe heart disease (including susceptibility to arrhythmias), Weight or body habitus that will prevent a successful MRI study.

Sponsors & Collaborators

• London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's: lead

Study Sites (1)

Michael Silverman

London, Ontario, N6A 4V2, Canada

Location

Related Publications (7)

• Vrieze A, Van Nood E, Holleman F, Salojarvi J, Kootte RS, Bartelsman JF, Dallinga-Thie GM, Ackermans MT, Serlie MJ, Oozeer R, Derrien M, Druesne A, Van Hylckama Vlieg JE, Bloks VW, Groen AK, Heilig HG, Zoetendal EG, Stroes ES, de Vos WM, Hoekstra JB, Nieuwdorp M. Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome. Gastroenterology. 2012 Oct;143(4):913-6.e7. doi: 10.1053/j.gastro.2012.06.031. Epub 2012 Jun 20.

  PMID: 22728514 BACKGROUND

• van Nood E, Vrieze A, Nieuwdorp M, Fuentes S, Zoetendal EG, de Vos WM, Visser CE, Kuijper EJ, Bartelsman JF, Tijssen JG, Speelman P, Dijkgraaf MG, Keller JJ. Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med. 2013 Jan 31;368(5):407-15. doi: 10.1056/NEJMoa1205037. Epub 2013 Jan 16.

  PMID: 23323867 BACKGROUND

• Hamilton MJ, Weingarden AR, Sadowsky MJ, Khoruts A. Standardized frozen preparation for transplantation of fecal microbiota for recurrent Clostridium difficile infection. Am J Gastroenterol. 2012 May;107(5):761-7. doi: 10.1038/ajg.2011.482. Epub 2012 Jan 31.

  PMID: 22290405 BACKGROUND

• 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.

  PMID: 23542823 BACKGROUND

• Bailey LC, Forrest CB, Zhang P, Richards TM, Livshits A, DeRusso PA. Association of antibiotics in infancy with early childhood obesity. JAMA Pediatr. 2014 Nov;168(11):1063-9. doi: 10.1001/jamapediatrics.2014.1539.

  PMID: 25265089 BACKGROUND

• Aghara H, Patel M, Chadha P, Parwani K, Chaturvedi R, Mandal P. Unraveling the Gut-Liver-Brain Axis: Microbiome, Inflammation, and Emerging Therapeutic Approaches. Mediators Inflamm. 2025 Jun 18;2025:6733477. doi: 10.1155/mi/6733477. eCollection 2025.

  PMID: 40568349 DERIVED

• Craven L, Rahman A, Nair Parvathy S, Beaton M, Silverman J, Qumosani K, Hramiak I, Hegele R, Joy T, Meddings J, Urquhart B, Harvie R, McKenzie C, Summers K, Reid G, Burton JP, Silverman M. Allogenic Fecal Microbiota Transplantation in Patients With Nonalcoholic Fatty Liver Disease Improves Abnormal Small Intestinal Permeability: A Randomized Control Trial. Am J Gastroenterol. 2020 Jul;115(7):1055-1065. doi: 10.14309/ajg.0000000000000661.

  PMID: 32618656 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus; Non-alcoholic Fatty Liver Disease; Metabolic Diseases; Obesity

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Nutritional and Metabolic Diseases; Endocrine System Diseases; Fatty Liver; Liver Diseases; Digestive System Diseases; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Michael Silverman, MD

  London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 7, 2015
• First Posted: July 14, 2015
• Study Start: June 1, 2016
• Primary Completion: April 1, 2018
• Study Completion: December 1, 2018
• Last Updated: December 11, 2018

Record last verified: 2018-12

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)