Clinical trial NCT04263376: Bariatric Surgery-Induced Shift in Gut Microbiome and NAFLD
Official title: Can Bariatric Surgery-Induced Shift in Gut Microbiome Protect Against Non-Alcoholic Fatty Liver Disease? A Step Toward Replicating Metabolic Surgery Results Without Surgery
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Obesity
Diabetes Mellitus, Type 2
NAFLD
Lead sponsor: The Cleveland Clinic
Sponsor class: OTHER
First posted: 2020-02-10
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Participants who are in the evaluation process for Roux-en-Y Gastric Bypass (RYGB) and Sleeve Gastrectomy (SG) will be offered the opportunity to volunteer for this study.

Brief summary: This study is designed as a prospective pilot study for longitudinal assessment of fecal microbiome related to medical and surgical weight loss. The investigators follow the standard of care for perioperative and intraoperative management of study participants. The only addition to the standard of care protocol will be collection of fecal samples at 3 time points. This will enable investigators to compare changes in and effects by microbiota after low-calorie diet versus after bariatric surgery .


Eligibility criteria: Inclusion Criteria:

* Be an eligible candidate for bariatric surgery based on standard criteria in place, have been enrolled in bariatric surgery program at Cleveland Clinic Main Campus, and have been cleared and approved for bariatric surgery by the BMI bariatric program and his/her health insurance
* Have a Body Mass Index (BMI) more than 35 kg/m2
* Have type 2 diabetes (T2D) (but not type 1 diabetes, see exclusion criteria) as defined by

  1. If untreated (as per ADA standards of care) FPG \> or = 126 mg/dL (7.0 mmol/L). Fasting is defined as no caloric intake for at least 8 h OR 2-h PG \> or = 200 mg/dL (11.1 mmol/L) during OGTT. The test should be performed as described by the WHO, using a glucose load containing the equivalent of 75-g anhydrous glucose dissolved in water OR A1C \> or = 6.5% (48 mmol/mol). The test should be performed in a laboratory using a method that is NGSP certified and standardized to the DCCT assay OR In a patient with classic symptoms of hyperglycemia or hyperglycemic crisis, a random plasma glucose \> or = 200 mg/dL (11.1 mmol/L).
  2. the use of any antidiabetic drug or glucose lowering agent, including biguanides (metformin), thiazolidinediones, alpha-glucosidase inhibitors, sulfonylurea, meglitinides, DPP4-inhibitors, GLP1-agonists, SGLT2i, any type of insulin.
* Have the ability and willingness to participate in the study and agree to the study terms
* As a standard of care, have a negative urine pregnancy test prior to surgery for women of childbearing potential. A woman of childbearing potential is one who is biologically capable of becoming pregnant. This includes women who are using contraceptives or whose sexual partners are either sterile or using contraceptives.

Exclusion Criteria:

* Any contra-indication for bariatric surgery (standard of care)
* Lack of insurance coverage for bariatric surgery
* Diabetes mellitus other than T2D including Type 1 diabetes or Latent Autoimmune Diabetes of the Adult (LADA) as defined by personal history of diabetic ketoacidosis or by positive auto-antibodies to glutamic Acid Decarboxylase (GAD-65), Islet Cell Antibodies (ICA), Insulin Autoantibodies (IAA), or to protein tyrosine phosphatase (IA-2A) Monogenetic or neonatal diabetes
* Prior bariatric surgery of any kind.
* Known history of chronic liver disease except for NAFLD/NASH: hepatitis, positive serologic test result for hepatitis B surface antigen and/or hepatitis C antibody, alpha-1-antitrypsin deficiency.
* Known Gastrointestinal disorders including a known history of celiac disease and/or any other malabsorptive disorders or inflammatory bowel disease (Crohn's disease or ulcerative colitis).
* Psychiatric disorders including dementia, active psychosis, severe depression requiring \> 2 medications, history of suicide attempts, alcohol or drug abuse within the previous 12 months.
* Smoking within the previous 3 months.
* Pregnancy.
* Malignancy within five years (except squamous cell and basal cell cancer of the skin). Subjects diagnosed with early / stage 1 cancer that have been successfully treated are eligible per Investigator discretion.
* Use of any medications (prescription or OTC), including herbal or other supplements for treatment of obesity, or liver conditions at the time of consent.
* Any condition or major illness that, in the investigator's judgment, places the subject at undue risk by participating in the study.
* Unable to understand the risks, realistic benefits and compliance requirements of each program.
* Use of investigational therapy or participation in any other clinical trial within 12 weeks prior to signing the ICF.

Primary outcomes:
measure: Changes in human gut microbiota
timeFrame: 3 months after surgery
Secondary outcomes:
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
Study officials:
affiliation: The Cleveland Clinic
name: Ali Aminian, MD
role: PRINCIPAL_INVESTIGATOR
References: