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

Obesity Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03789461
• Other study ID #: FMT-OB study
• Status: Active, not recruiting
• Phase: N/A
• Start date: December 28, 2018
• Est. completion date: December 2022

Study information

• Verified date: February 2022
• Source: Chinese University of Hong Kong
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 20
• Est. completion date: December 2022
• Est. primary completion date: December 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Obesity
• Weight Loss

Intervention

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

Locations

Country	Name	City	State
Hong Kong	The Chinese University of Hong Kong	Hong Kong

Sponsors (1)

Lead Sponsor	Collaborator
Chinese University of Hong Kong

Country where clinical trial is conducted

Hong Kong, 

References & Publications (10)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of at least 10% reduction in weight	Determine the proportion of at least 10% reduction in weight compared with baseline weight	6 weeks
Secondary	Proportion of subjects maintaining weight reduction	Proportion of subjects maintaining at least 10% reduction in weight compared with baseline	12, 26, 52, 78, 104 weeks
Secondary	Proportion of subjects maintaining weight reduction	Proportion of subjects maintaining at least 5% reduction in weight compared with baseline	6,12, 26, 52, 78, 104 weeks
Secondary	Changes in waist circumference	Changes in waist circumference compared with baseline	6,12, 26, 52, 78, 104 weeks
Secondary	Decrease in waist to hip ratio and in total body weight	At least 5% decrease in waist to hip ratio and in total body weight	6,12, 26, 52, 78, 104 weeks
Secondary	Change in biochemical parameters	Study samples will collected to characterize which microbiota favors FMT by performing metagenomics of gut microbiome in stool samples	6 weeks