Longitudinal Phenotyping of Bariatric Surgery Patients

• Sponsor: Imperial College London (Other)
• Overall Status: Completed
• CT.gov ID: NCT02421055
• Collaborator: (none)
• Enrollment: 158
• Location: 1
• Actual Duration (Months): 44.1
• Patients Per Site Per Month: 3.6

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Obesity; Diabetes Mellitus, Type 2	Procedure: Laparoscopic Roux-en-Y Gastric Bypass; Procedure: Laparoscopic Sleeve Gastrectomy

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.

Study Design

• Study Type: Observational [Patient Registry]
• Actual Enrollment: 158 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Longitudinal Phenotyping of Bariatric Surgery Patients
• Actual Study Start Date: Jun 1, 2015
• Actual Primary Completion Date: Feb 1, 2019
• Actual Study Completion Date: Feb 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Group 1 Roux-en-Y Gastric Bypass	Procedure: Laparoscopic Roux-en-Y Gastric Bypass
Group 2 Sleeve Gastrectomy	Procedure: Laparoscopic Sleeve Gastrectomy

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Complete Diabetes Remission at 3 Months [3 months]

   Participants with HbA1c <6% (42mmol/mol), off anti-diabetic medication, at 3 months

Secondary Outcome Measures

1. Partial Diabetes Remission [3 months]

   HbA1c <6.5% (48mmol/mol), off anti-diabetic medication, at 3 months. (Includes participants with complete remission).

2. HbA1c Improvement [3 months]

   Reduction in HbA1c at 3 months

3. Weight Loss [3 months]

   Weight loss at 3 months

4. BMI Reduction [3 months]

   BMI reduction at 3 months

5. Complete Diabetes Remission [1 year]

   HbA1c <6% (42mmol/mol), off anti-diabetic medication, at 1 year

6. Partial Diabetes Remission [1 year]

   HbA1c <6.5% (48mmol/mol), off anti-diabetic medication, at 1 year. (Includes participants with complete diabetes remission).

7. HbA1c Improvement [1 year]

   Reduction in HbA1c at 1 year

8. Weight Loss [1 year]

   Weight loss at 1 year

9. BMI Reduction [1 year]

   BMI reduction at 1 year

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Imperial Weight Centre	London		United Kingdom	W2 1NY

Sponsors and Collaborators

• Imperial College London

Investigators

• Principal Investigator: Ara Darzi, MB, BCh, MD, Imperial College London

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Feb 16, 2019

More Information

Publications

None provided.

• Responsible Party: Imperial College London
• ClinicalTrials.gov Identifier: NCT02421055
• Other Study ID Numbers: 15SM2479
• First Posted: Apr 20, 2015
• Last Update Posted: Nov 6, 2020
• Last Verified: Oct 1, 2020

• Keywords provided by Imperial College London: Bariatric Surgery; Gastric Bypass; Sleeve Gastrectomy; Gastroplasty
• Additional relevant MeSH terms: Diabetes Mellitus, Type 2

Study Results

Participant Flow

Pre-assignment Detail	Some participants consented to give serum samples only, others were able to give complete sets of serum, 24-hour urine and stool, as detailed below.

Arm/Group Title	Pre-operative Only	Roux-en-Y Gastric Bypass (RYGB)	Vertical Sleeve Gastrectomy (VSG)
Arm/Group Description	Recruited patients that did not undergo RYGB or VSG procedures	Participants who underwent RYGB procedure	Participants who underwent VSG procedure
Period Title: Overall Study
STARTED	34	50	74
Pre-operative Serum Sample (Minimum)	34	50	74
Pre-operative Complete Sample Set	23	22	36
Post-operative Serum Sample (Minimum)	0	23	26
Post-operative Complete Sample Set	0	13	14
COMPLETED	0	50	74
NOT COMPLETED	34	0	0

Baseline Characteristics

Arm/Group Title	Roux-en-Y Gastric Bypass (RYGB)	Vertical Sleeve Gastrectomy (VSG)	Total
Arm/Group Description	50 participants gave pre-operative serum samples prior to undergoing RYGB. 23 participants underwent RYGB and gave serum samples pre and 3-months post-operatively. 13 of these gave complete sample sets of serum, 24-hour urine and stool pre and 3-months post-operation.	74 participants gave pre-operative serum samples prior to undergoing VSG. 26 participants underwent VSG and gave serum samples pre and 3-months post-operatively. 14 of these gave complete sample sets of serum, 24-hour urine and stool pre and 3-months post-operation.	Total of all reporting groups
Overall Participants	50	74	124
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	46.54 (11.04)	44.01 (11.91)	45.03 (11.59)
Sex: Female, Male (Count of Participants)
Female	41 82%	49 66.2%	90 72.6%
Male	9 18%	25 33.8%	34 27.4%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (participants) [Number]
United Kingdom	50 100%	74 100%	124 100%
Weight (Kg) (Kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Kg]	120.86 (20.17)	133.6 (30.35)	128.14 (27.29)
BMI (kg/m2) (Kg/m2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Kg/m2]	44.43 (5.69)	47.12 (8.99)	46.03 (7.91)
Diabetes Status (Count of Participants)
Type 2 Diabetes (T2D)	27 54%	24 32.4%	51 41.1%
Impaired Glucose Tolerence (IGT)	7 14%	13 17.6%	20 16.1%
Non-diabetic	16 32%	37 50%	53 42.7%
HBA1c (mmols/mol) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmols/mol]	52.24 (17.66)	45.41 (12.82)	48.16 (15.27)
Metformin use (Count of Participants)
Count of Participants [Participants]	26 52%	22 29.7%	48 38.7%
Insulin use (Count of Participants)
Count of Participants [Participants]	10 20%	5 6.8%	15 12.1%
Duration of T2D (years) (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	7.96 (7.03)	7.75 (8.47)	7.86 (7.66)

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Complete Diabetes Remission at 3 Months
Description	Participants with HbA1c <6% (42mmol/mol), off anti-diabetic medication, at 3 months
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

Participants with complete follow up data

Arm/Group Title	Roux-en-Y Gastric Bypass	Vertical Sleeve Gastrectomy
Arm/Group Description	Participants who underwent Roux-en-Y Gastric Bypass	Participants who underwent Vertical Sleeve Gastrectomy
Measure Participants	18	16
Count of Participants [Participants]	8 16%	5 6.8%

2. Secondary Outcome

Title	Partial Diabetes Remission
Description	HbA1c <6.5% (48mmol/mol), off anti-diabetic medication, at 3 months. (Includes participants with complete remission).
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

Participants with complete follow up data

Arm/Group Title	Group 1	Group 2
Arm/Group Description	Roux-en-Y Gastric Bypass	Vertical Sleeve Gastrectomy
Measure Participants	18	16
Count of Participants [Participants]	9 18%	6 8.1%

3. Secondary Outcome

Title	HbA1c Improvement
Description	Reduction in HbA1c at 3 months
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

Participants attending follow up

Arm/Group Title	Group 1	Group 2
Arm/Group Description	Roux-en-Y Gastric Bypass	Vertical Sleeve Gastrectomy
Measure Participants	44	67
Mean (Standard Deviation) [mmols/mol]	12.0 (11.98)	7.53 (10.18)

4. Secondary Outcome

Title	Weight Loss
Description	Weight loss at 3 months
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

Participants attending follow up

Arm/Group Title	Group 1	Group 2
Arm/Group Description	Roux-en-Y Gastric Bypass	Vertical Sleeve Gastrectomy
Measure Participants	44	67
Mean (Standard Deviation) [Kg/m2]	24.13 (9.13)	24.00 (7.94)

5. Secondary Outcome

Title	BMI Reduction
Description	BMI reduction at 3 months
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

Participants attending follow up

Arm/Group Title	Group 1	Group 2
Arm/Group Description	Roux-en-Y Gastric Bypass	Vertical Sleeve Gastrectomy
Measure Participants	44	67
Mean (Standard Deviation) [Kg/m2]	8.87 (2.99)	8.51 (2.62)

6. Secondary Outcome

Title	Complete Diabetes Remission
Description	HbA1c <6% (42mmol/mol), off anti-diabetic medication, at 1 year
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

Participants with complete follow up data

Arm/Group Title	Group 1	Group 2
Arm/Group Description	Roux-en-Y Gastric Bypass	Vertical Sleeve Gastrectomy
Measure Participants	15	12
Count of Participants [Participants]	10 20%	4 5.4%

7. Secondary Outcome

Title	Partial Diabetes Remission
Description	HbA1c <6.5% (48mmol/mol), off anti-diabetic medication, at 1 year. (Includes participants with complete diabetes remission).
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

Participants with complete follow up data

Arm/Group Title	Group 1	Group 2
Arm/Group Description	Roux-en-Y Gastric Bypass	Vertical Sleeve Gastrectomy
Measure Participants	15	12
Count of Participants [Participants]	10 20%	5 6.8%

8. Secondary Outcome

Title	HbA1c Improvement
Description	Reduction in HbA1c at 1 year
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

Participants attending follow up

Arm/Group Title	Group 1	Group 2
Arm/Group Description	Roux-en-Y Gastric Bypass	Vertical Sleeve Gastrectomy
Measure Participants	36	57
Mean (Standard Deviation) [mmols/mol]	13.72 (13.71)	6.88 (10.19)

9. Secondary Outcome

Title	Weight Loss
Description	Weight loss at 1 year
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

Participants attending follow up

Arm/Group Title	Group 1	Group 2
Arm/Group Description	Roux-en-Y Gastric Bypass	Vertical Sleeve Gastrectomy
Measure Participants	36	57
Mean (Standard Deviation) [Kg]	37.53 (11.36)	35.23 (12.98)

10. Secondary Outcome

Title	BMI Reduction
Description	BMI reduction at 1 year
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

Participants attending follow up

Arm/Group Title	Group 1	Group 2
Arm/Group Description	Roux-en-Y Gastric Bypass	Vertical Sleeve Gastrectomy
Measure Participants	36	57
Mean (Standard Deviation) [Kg/m2]	13.8 (3.69)	13.02 (5.54)

Adverse Events

Time Frame	1 year
Adverse Event Reporting Description	Serious, and other adverse events were not monitored/assessed. None occurred as a result of this observational study.
Arm/Group Title	Pre-operative Samples Only		Roux-en-Y Gastric Bypass		Vertical Sleeve Gastrectomy
Arm/Group Description	Recruited patients that did not undergo RYGB or VSG procedures		Participants who underwent RYGB		Participants who underwent VSG
All Cause Mortality
	Pre-operative Samples Only		Roux-en-Y Gastric Bypass		Vertical Sleeve Gastrectomy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/34 (0%)		0/50 (0%)		0/74 (0%)
Serious Adverse Events
	Pre-operative Samples Only		Roux-en-Y Gastric Bypass		Vertical Sleeve Gastrectomy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)		0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Pre-operative Samples Only		Roux-en-Y Gastric Bypass		Vertical Sleeve Gastrectomy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)		0/0 (NaN)

Limitations/Caveats

Complete sets of serum, 24-hour urine and faeces were not collected from all participants. Details are described in baseline group descriptions.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.