Gut Hormones and Roux en Y Gastric Bypass

Imperial College London

Status: Enrolling

Conditions: Obesity; Type 2 Diabetes

Treatments: Other: Very low calorie diet; Other: Gut hormone infusion; Other: Placebo infusion; Procedure: Roux en Y Gastric Bypass Surgery

Study type: Interventional

Funder types: Other

Identifiers

NCT01945840

MR/K02115X/1

Details and patient eligibility

About

The purpose of this study is to assess whether the changes in gut hormones seen following Roux en Y Gastric Bypass surgery are responsible for some of the beneficial effects seen post-operatively.

Full description

This study is designed to investigate whether chronic elevation of glucagon-like peptide-1 (GLP-1), oxyntomodulin and peptide YY (PYY) in combination is responsible for the majority of the metabolic effects of Roux-en-Y gastric bypass (RYGB) including improved glycaemia, increased energy expenditure, reduced food intake, weight loss, reduced preference for high calorie foods and reduced activation in brain reward areas in response to visual food cues.

Enrollment: 190 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

Inclusion criteria

• Aged 18 - 70 years.
• Male or female.
• Eligible for bariatric surgery under the NHS.
• Diagnosed with impaired glucose regulation or type 2 diabetes, according to WHO 2011 criteria.
• Those with diabetes should be stable and well controlled with either diet or one oral hypoglycaemic agent.
• HbA1c ≤9.0% or 74.9 mmol/mol.

Exclusion criteria

• History of any medical, psychological or other condition, or use of any medications, including over-the-counter products, which, in the opinion of the investigators, would either interfere with the study or potentially cause harm to the volunteer.

• Without access at home to a telephone or other factor likely to interfere with ability to participate reliably in the study.

• Pregnancy or breastfeeding.

• Smokers.

• Unable to maintain adequate contraception for the duration of the study and for one month afterwards.

• History of hypersensitivity to any of the components of the subcutaneous infusions.

• Donated blood during the preceding 3 months or intention to do so before the end of the study.

• Insulin treatment.

• Uncontrolled hypertension.

• Any other co-morbidity that would compromise the validity of the study or the safety of the participant such as heart failure, clinically apparent cardiovascular disease.

• Volunteers on anti-coagulants such as warfarin and factor Xa inhibitors will not undergo adipose tissue biopsy.

• Unable to give informed consent.

• Previous bariatric surgery.

• Unable to undergo fMRI due to:

  • Claustrophobia.
  • Pacemaker, metal implant, clips, implanted device, shrapnel or bullet, metal in eyes that precludes magnetic resonance imaging.
  • Significant structural abnormality on magnetic resonance brain scan

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

---

190 participants in 4 patient groups, including a placebo group

Roux en Y Gastric Bypass

Active Comparator group

Description:

Participants will be those already scheduled to undergo Roux en Y Gastric Bypass Surgery

Treatment:

Procedure: Roux en Y Gastric Bypass Surgery

Gut hormone infusion

Experimental group

Description:

Infusion of three gut hormones (GLP-1, PYY and oxyntomodulin) subcutaneously for 4 weeks as below: * Combination of GLP-1/OXM/PYY (GOP) * Single GLP-1 * Single OXM * Single PYY * Combination of GLP-1 and OXM * Combination of GLP-1 and PYY * Combination of OXM and PYY

Treatment:

Other: Gut hormone infusion

Placebo infusion

Placebo Comparator group

Description:

Saline infusion given subcutaneously for 4 weeks.

Treatment:

Other: Placebo infusion

Very low calorie diet

Active Comparator group

Description:

Participants will be asked to follow a very low calorie diet for 4 weeks.

Treatment:

Other: Very low calorie diet