Longitudinal Phenotyping of Bariatric Surgery Patients
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|ClinicalTrials.gov Identifier: NCT02421055|
Recruitment Status : Active, not recruiting
First Posted : April 20, 2015
Last Update Posted : August 21, 2017
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.
|Condition or disease||Intervention/treatment|
|Obesity Diabetes Mellitus, Type 2||Procedure: Laparoscopic Roux-en-Y Gastric Bypass Procedure: Laparoscopic Sleeve Gastrectomy|
In this study we aim 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.
We will longitudinally phenotype 130 obese diabetics undergoing Roux-en-Y Gastric Bypass or Sleeve Gastrectomy surgery. Patients will be assessed preoperatively and at 3 months and 1 year postoperatively. The primary clinical outcome will be diabetes remission. Other clinical measures recorded will include; 1) anthropometric & physiological measurements, 2) demographic details, 3) biochemical parameters, 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 16S rRNA sequencing and qPCR. Selected responders and non-responders will undergo full shotgun metagenomic and metatranscriptomic analysis. 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.
We 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.
|Study Type :||Observational [Patient Registry]|
|Estimated Enrollment :||130 participants|
|Target Follow-Up Duration:||2 Years|
|Official Title:||Longitudinal Phenotyping of Bariatric Surgery Patients|
|Study Start Date :||June 2015|
|Estimated Primary Completion Date :||December 2018|
|Estimated Study Completion Date :||December 2018|
Roux-en-Y Gastric Bypass
Procedure: Laparoscopic Roux-en-Y Gastric Bypass
Procedure: Laparoscopic Sleeve Gastrectomy
- Complete diabetes remission [ Time Frame: 3 months ]HbA1c <6% (42mmol/mol), off anti-diabetic medication
- Partial diabetes remission [ Time Frame: 3 months ]HbA1c <6.5% (48mmol/mol), off anti-diabetic medication
- Diabetes improvement [ Time Frame: 3 months ]Change in HbA1c
- Weight loss [ Time Frame: 3 months ]% excess weight loss
- Complete diabetes remission [ Time Frame: 1 year ]HbA1c <6% (42mmol/mol), off anti-diabetic medication
- Partial diabetes remission [ Time Frame: 1 year ]HbA1c <6.5% (48mmol/mol), off anti-diabetic medication
- Diabetes improvement [ Time Frame: 1 year ]Change in HbA1c
- Weight loss [ Time Frame: 1 year ]% excess weight loss
Biospecimen Retention: Samples With DNA
Serum, urine and stool preoperatively and at 3 months and 1 year postoperatively.
Resected stomach tissue from patients undergoing Sleeve Gastrectomy.
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): NCT02421055
|Imperial Weight Centre|
|London, United Kingdom, W2 1NY|
|Principal Investigator:||Ara Darzi, MB, BCh, MD||Imperial College London|