Clinical trial NCT02421055: Longitudinal Phenotyping of Bariatric Surgery Patients
Official title: Longitudinal Phenotyping of Bariatric Surgery Patients
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Obesity
Diabetes Mellitus, Type 2
Keywords: Bariatric Surgery
Gastric Bypass
Sleeve Gastrectomy
Gastroplasty
Lead sponsor: Imperial College London
Sponsor class: OTHER
First posted: 2015-04-20
Enrollment: 158
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Participants with obesity undergoing bariatric surgery

Brief summary: Recent studies have shown that bacteria within the gut play an important role in diabetes improvement after bariatric (weight-loss) surgery. Bariatric surgery fundamentally changes the environment within the gut, which results in changes to the makeup of the trillions of bacteria living within it. These changes in the gut bacteria can affect the body in a number of complex ways, which we are only just beginning to understand. For example, gut bacteria breakdown food we are unable to absorb ourselves, leading to altered sugar levels and can release molecules that act to reduce appetite.

In this study we aim to find out how bariatric surgery changes the gut bacteria and how this leads to weight loss and improvement of diabetes. With this understanding we hope to discover potential targets for future treatments, such as identifying beneficial bacteria that could be supplemented with probiotics in patients.

Additionally, although highly successful, up to 30% of obese patients do not undergo improvement of their diabetes after bariatric surgery. We aim to identify molecules within the patient's blood or urine that are able to predict the likely chance a patient will undergo improvement in their diabetes after bariatric surgery to help clinicians select patients most likely to benefit.

Detailed description: This study aims to assess how the gut microbiome affects the host phenotype following bariatric surgery through altered gut microbiome-host co-metabolism. The secondary objective is to identify novel biomarkers for the preoperative prognostication of T2DM remission following bariatric surgery.

The study will longitudinally phenotype obese diabetics and non-diabetics undergoing Roux-en-Y Gastric Bypass or Sleeve Gastrectomy surgery. Patients will be assessed preoperatively and at 3 months and 1 year postoperatively. Clinical measures recorded will include; 1) anthropometric \& physiological measurements, 2) demographic details, 3) biochemical parameters including HbA1c, 4) anti-hyperglycaemic and other medication use, 5) co-morbidity status and 6) dietary choices through 24hr dietary recall questionnaires.

Blood, urine and stool samples will be collected at the above time points. Changes to the microbiome will be assessed using metagenomic sequencing. Global metabonomic profiles of serum, urine and faecal water will be generated using 1H-NMR. Further targeted analyses of bile acid and short-chain fatty acid profiles will be performed using LC-MS / GC-MS.

The study will utilise multivariate statistical analysis techniques to identify metabolic pathways altered following intervention, and novel host-microbiome co-metabolism pathways that impact upon phenotype. A supervised multivariate analysis, mapping T2DM outcomes to metagenomic and metabonomic data will be performed with the aim of identifying novel preoperative biomarkers that are able to prognosticate T2DM resolution following bariatric surgery.

Eligibility criteria: Inclusion Criteria:

* Obese (BMI\>30kg/m2)
* Type 2 Diabetes Mellitus and non-diabetic
* Failure of efforts at lifestyle modification and dieting
* Fitness for anaesthesia and procedure
* Willingness to comply with the trial protocol

Exclusion Criteria:

* Previous bariatric surgery
* Pregnancy or intention to become pregnant during trial period
* Lack of capacity to consent
* Previous major abdominal surgery (Small or large bowel resection, stomach, liver, pancreatic or splenic surgery. Does not include patients who have previously had an appendicectomy, cholecystectomy or hernia repair).

Primary outcomes:
measure: Number of Participants With Complete Diabetes Remission at 3 Months
timeFrame: 3 months
Secondary outcomes:
measure: Partial Diabetes Remission
timeFrame: 3 months
measure: HbA1c Improvement
timeFrame: 3 months
measure: Weight Loss
timeFrame: 3 months
measure: BMI Reduction
timeFrame: 3 months
measure: Complete Diabetes Remission
timeFrame: 1 year
measure: Partial Diabetes Remission
timeFrame: 1 year
measure: HbA1c Improvement
timeFrame: 1 year
measure: Weight Loss
timeFrame: 1 year
measure: BMI Reduction
timeFrame: 1 year
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Imperial Weight Centre
Study officials:
affiliation: Imperial College London
name: Ara Darzi, MB, BCh, MD
role: PRINCIPAL_INVESTIGATOR
References: