Fecal Microbiota Transplant (FMT) to Induce Weight Loss in Obese Subjects

• ClinicalTrials.gov Identifier: NCT03789461
• Recruitment Status: Recruiting
• First Posted: December 28, 2018
• Last Update Posted: March 5, 2019
• Sponsor: Chinese University of Hong Kong
• Information provided by (Responsible Party): Siew Chien NG, Chinese University of Hong Kong

Tracking Information

• First Submitted Date: December 24, 2018
• First Posted Date: December 28, 2018
• Last Update Posted Date: March 5, 2019
• Actual Study Start Date: December 28, 2018
• Estimated Primary Completion Date: October 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 27, 2018)

Proportion of at least 10% reduction in weight [ Time Frame: 6 weeks ]

Determine the proportion of at least 10% reduction in weight compared with baseline weight

• Original Primary Outcome Measures: Same as current
• Change History: Complete list of historical versions of study NCT03789461 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: December 27, 2018)

• Proportion of subjects maintaining weight reduction [ Time Frame: 12, 26, 52, 78, 104 weeks ]
  Proportion of subjects maintaining at least 10% reduction in weight compared with baseline
• Proportion of subjects maintaining weight reduction [ Time Frame: 6,12, 26, 52, 78, 104 weeks ]
  Proportion of subjects maintaining at least 5% reduction in weight compared with baseline
• Changes in waist circumference [ Time Frame: 6,12, 26, 52, 78, 104 weeks ]
  Changes in waist circumference compared with baseline
• Decrease in waist to hip ratio and in total body weight [ Time Frame: 6,12, 26, 52, 78, 104 weeks ]
  At least 5% decrease in waist to hip ratio and in total body weight
• Change in biochemical parameters [ Time Frame: 6 weeks ]
  Study samples will collected to characterize which microbiota favors FMT by performing metagenomics of gut microbiome in stool samples

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Fecal Microbiota Transplant (FMT) to Induce Weight Loss in Obese Subjects
• Official Title: An Open-label Pilot Study of Fecal Microbiota Transplant (FMT) to Induce Weight Loss in Obese Subjects

Brief Summary

Obesity is associated with changes in the composition of the intestinal microbiota, and the obese microbiome appears to be more efficient in harvesting energy from the diet.

Fecal microbiota transplantation (FMT) represents a clinically feasible way to restore the gut microbial ecology, and has proven to be a breakthrough for the treatment of recurrent Clostridium difficile infection.

The therapy is generally well tolerated and appeared safe. No clinical studies have assessed the dosage of FMT in obese subjects.

Detailed Description

Recently, accumulating evidence supports a role of the enteric microbiota in the pathogenesis of obesity-related insulin resistance. Obesity is associated with changes in the composition of the intestinal microbiota, and the obese microbiome appears to be more efficient in harvesting energy from the diet. Colonization of germ-free mice with an 'obese microbiota' results in a significantly greater increase in total body fat than colonization with a 'lean microbiota', suggesting gut microbiota as an additional contributing factor to the pathophysiology of obesity. Obese and lean phenotypes can also be induced in germ-free mice by transfer of fecal microbiota from human donors. These data have led to the use of microbiota therapeutics as a potential treatment for metabolic syndrome and obesity.

Fecal microbiota transplantation (FMT) represents a clinically feasible way to restore the gut microbial ecology, and has proven to be a breakthrough for the treatment of recurrent Clostridium difficile infection. Furthermore, clinical trials are being conducted to evaluate its use for other conditions including inflammatory bowel disease, irritable bowel syndrome, diabetes mellitus, non-alcoholic steatohepatitis and hepatic encephalopathy. Early results in human have shown that FMT from lean donor when transplanted into subjects with metabolic syndrome resulted in a significant improvement in insulin sensitivity and an increased in intestinal microbial diversity, including a distinct increase in butyrate-producing bacterial strains. The therapy is generally well tolerated and appeared safe. No clinical studies have assessed the dosage of FMT in obese subjects.

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Obesity

Intervention

Procedure: Fecal Microbiota Transplantation

FMT infusion (100-200ml) and Mucosal Microbiota Assessment (To assess the fecal and mucosal microbiota before and after FMT)

Study Arms

Experimental: Fecal Microbiota Transplantation

FMT infusion

Intervention: Procedure: Fecal Microbiota Transplantation

Publications *

• Turnbaugh PJ, Hamady M, Yatsunenko T, Cantarel BL, Duncan A, Ley RE, Sogin ML, Jones WJ, Roe BA, Affourtit JP, Egholm M, Henrissat B, Heath AC, Knight R, Gordon JI. A core gut microbiome in obese and lean twins. Nature. 2009 Jan 22;457(7228):480-4. doi: 10.1038/nature07540. Epub 2008 Nov 30.
• Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature. 2006 Dec 21;444(7122):1027-31.
• Ridaura VK, Faith JJ, Rey FE, Cheng J, Duncan AE, Kau AL, Griffin NW, Lombard V, Henrissat B, Bain JR, Muehlbauer MJ, Ilkayeva O, Semenkovich CF, Funai K, Hayashi DK, Lyle BJ, Martini MC, Ursell LK, Clemente JC, Van Treuren W, Walters WA, Knight R, Newgard CB, Heath AC, Gordon JI. Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science. 2013 Sep 6;341(6150):1241214. doi: 10.1126/science.1241214.
• Smith MI, Yatsunenko T, Manary MJ, Trehan I, Mkakosya R, Cheng J, Kau AL, Rich SS, Concannon P, Mychaleckyj JC, Liu J, Houpt E, Li JV, Holmes E, Nicholson J, Knights D, Ursell LK, Knight R, Gordon JI. Gut microbiomes of Malawian twin pairs discordant for kwashiorkor. Science. 2013 Feb 1;339(6119):548-54. doi: 10.1126/science.1229000. Epub 2013 Jan 30.
• 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.
• Moayyedi P, Surette MG, Kim PT, Libertucci J, Wolfe M, Onischi C, Armstrong D, Marshall JK, Kassam Z, Reinisch W, Lee CH. Fecal Microbiota Transplantation Induces Remission in Patients With Active Ulcerative Colitis in a Randomized Controlled Trial. Gastroenterology. 2015 Jul;149(1):102-109.e6. doi: 10.1053/j.gastro.2015.04.001. Epub 2015 Apr 7.
• Vrieze A, Van Nood E, Holleman F, Salojärvi 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. Erratum in: Gastroenterology. 2013 Jan;144(1):250.
• Kelly CR, Kahn S, Kashyap P, Laine L, Rubin D, Atreja A, Moore T, Wu G. Update on Fecal Microbiota Transplantation 2015: Indications, Methodologies, Mechanisms, and Outlook. Gastroenterology. 2015 Jul;149(1):223-37. doi: 10.1053/j.gastro.2015.05.008. Epub 2015 May 15. Review.
• Kassam Z, Lee CH, Yuan Y, Hunt RH. Fecal microbiota transplantation for Clostridium difficile infection: systematic review and meta-analysis. Am J Gastroenterol. 2013 Apr;108(4):500-8. doi: 10.1038/ajg.2013.59. Epub 2013 Mar 19. Review.
• Wong SK, Kong AP, Mui WL, So WY, Tsung BY, Yau PY, Chow FC, Ng EK. Laparoscopic bariatric surgery: a five-year review. Hong Kong Med J. 2009 Apr;15(2):100-9.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: December 27, 2018): 20
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: May 2021
• Estimated Primary Completion Date: October 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Age 18-75; and
2. BMI ≥28 kg/m^2 and < 45 kg/m^2; and
3. Written informed consent obtained

Exclusion Criteria:

1. Current pregnancy
2. Known history or concomitant significant gastrointestinal disorders (including Inflammatory Bowel Disease, current colorectal cancer)
3. Known history or concomitant significant food allergies
4. Immunosuppressed subjects
5. Known history of severe organ failure (including decompensated cirrhosis), kidney failure, epilepsy, acquired immunodeficiency syndrome
6. Current active sepsis
7. Known contraindications to oesophago-gastro-duodenoscopy (OGD)
8. Use of probiotic or antibiotics in recent 3 months
9. New drugs in the last three months that can impact on metabolism or body weight
10. Previous gastric or small intestinal surgery that alters gut anatomy such as fundoplication, gastric resection, gastric bypass, small bowel resection, ileoectomy, colectomy
11. Patients who have a confirmed current active malignancy or cancer

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Amy LI; +852 26373225; amyli@cuhk.edu.hk

Contact: Kitty Cheung; +852 26373260; kittyccy@cuhk.edu.hk

• Listed Location Countries: Hong Kong

Administrative Information

• NCT Number: NCT03789461
• Other Study ID Numbers: FMT-OB study
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Responsible Party: Siew Chien NG, Chinese University of Hong Kong
• Study Sponsor: Chinese University of Hong Kong
• Collaborators: Not Provided

Investigators

• Principal Investigator: Siew NG, Prof.; Chinese University of Hong Kong

• PRS Account: Chinese University of Hong Kong
• Verification Date: March 2019