Intestinal Microbiota and NAFLD Pre and Post Bariatric Surgery
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT01856465|
Recruitment Status : Recruiting
First Posted : May 17, 2013
Last Update Posted : November 17, 2017
|Condition or disease|
|Morbid Obesity Non-alcoholic Fatty Liver Disease|
Study Design: A. Cross-sectional study: Sixty patients with morbid obesity undergoing bariatric surgery diagnosed with NAFLD on liver biopsy (30 SS, 30 NASH). Main hypothesis: The ratio of Firmicutes/Bacteroidetes is higher in stool samples from morbidly obese subjects with NASH compared to SS. Other differences in IM composition exist. Objective: to compare bacterial dynamics using Illumina technology to assess the IM. The relative abundance of the dominant fecal microorganisms (including Firmicutes, Archaea, Bacteroides, Bifidobacteria, Mollicutes, Enterobacteriaceae, Clostridia clusters, F. prausnitzii, Roseburia, and Lactobacilli) will also be assessed by real-time PCR. Sub-hypotheses: In NASH compared to SS, there will be: a) lower fecal butyrate concentration; b) higher endotoxin and other inflammatory markers (TNF-α, IL-6) in plasma. Potential covariates assessed: small intestinal bacterial overgrowth (SIBO), measured by glucose hydrogen breath test (GHBT), which can contribute to endotoxemia and inflammation; IR, diabetes status, lipid profile, plasma vitamin E, liver enzymes, anthropometry, food intake, physical activity and environmental factors.
B. Prospective cohort study: Patients undergoing bariatric surgery with either SS or NASH (up to 60 of them recruited from Part A) will be followed prospectively over 12 months to assess changes in the IM and liver histology. Goal is to have 60 subjects who complete the study with a 2nd liver biopsy. Main Hypothesis: In morbidly obese patients with NAFLD (SS or NASH), changes in IM post bariatric surgery will be associated with changes in liver histology. Specifically, an increased number of F. prausnitzii in feces with be associated with improvement in liver histology while a reduction will be associated with deterioration of liver histology. Objective: To correlate changes in liver histology (NAFLD activity score [NAS], inflammation, fibrosis, steatosis) between 0 and 12 months with changes in F. prausnitzii. Other changes of the fecal IM community structure, fecal short chain fatty acids (including butyrate), plasma endotoxin, inflammatory markers (TNF-α, IL-6) and SIBO will also be assessed, in addition to diet, activity, weight change, improvement of diabetes and plasma vitamin E. Secondary hypotheses: Increased number of F. prausnitzii in feces will be associated with increased fecal butyrate, lower serum endotoxin and lower inflammatory markers (TNF-α, IL-6) in plasma.
Significance: In humans with morbid obesity and NAFLD undergoing bariatric surgery, very little data are available on IM and its metabolic effect and contribution to NAFLD. These studies will add more information regarding the role of IM and its effect on potential mechanisms contributing to NAFLD. It will also provide us with pilot data for future intervention studies assessing the potential use of pre- or probiotics for NAFLD in morbidly obese subjects in the setting of bariatric surgery.
|Study Type :||Observational|
|Estimated Enrollment :||120 participants|
|Official Title:||Role of Intestinal Microbiota in Non-alcoholic Fatty Liver Disease Pre and Post bAriatric Surgery|
|Actual Study Start Date :||June 2013|
|Estimated Primary Completion Date :||December 2018|
|Estimated Study Completion Date :||August 2019|
U.S. FDA Resources
Bariatric surgery of morbid obese
Morbid obese patient who undergo Bariatric surgery with NAFLD (NASH or SS) status
- Firmicutes/Bacteroides ratio in feces [ Time Frame: Baseline, 6, 12 months ]16S rRNA sequencing will be performed on the Ion Torrent platform
- Overall microbiota composition, amount of selected groups of microorganisms and concentration of Short Chain Fatty Acid (SCFA) in stool sample [ Time Frame: 8 months ]Lower fecal butyrate concentration in NASH vs SS
- The amount of endotoxin, TNF-alfa and IL-6 in plasma/serum [ Time Frame: 8 months ]Higher plasma endotoxin and pro-inflammatory markers (TNF-alfa and IL-6) in NASH vs SS.
- The change in inflammation, fibrosis, steatosis in liver histology [ Time Frame: 12 months ]Change in the number of F. prausnitzii in stool between baseline and 12 months related with the change in liver histology
- NAFLD activity score [ Time Frame: baseline, 12 months ]NAFLD Activity score (Kleiner) on liver histology
Biospecimen Retention: Samples With DNA
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01856465
|Contact: Johane Allard, MD, FRCP||416-340-5159||Dr.Johane.Allard@uhn.ca|
|Contact: Carrie Li, CCRP, BScfirstname.lastname@example.org|
|University Health Network||Recruiting|
|Toronto, Ontario, Canada, M5G 2C4|
|Contact: Bianca M Arendt, PhD, CCRP 416-340-4104 email@example.com|
|Contact: Johane P Allard, MD 416-340-5159 firstname.lastname@example.org|
|Principal Investigator: Johane P Allard, MD|
|Principal Investigator:||Johane Allard, MD. FRCPC||University Health Network, Toronto|