Gut Hormones and Roux en Y Gastric Bypass

NCT01945840 | Recruiting DMC

• 1 other identifier: MR/K02115X/1
• Study Type: interventional
• Target: 190
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Obesity; Type 2 Diabetes

Outcome Measures

Primary Outcomes (1)

• Weight loss

  Weight loss as measured at baseline compared to 4 weeks after infusion or diet

  Baseline - 4 weeks

Secondary Outcomes (1)

• Glycaemia

  Baseline - 4 weeks

Study Arms (4)

Roux en Y Gastric Bypass

ACTIVE COMPARATOR

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

Procedure: Roux en Y Gastric Bypass Surgery

Gut hormone infusion

EXPERIMENTAL

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

Other: Gut hormone infusion

Placebo infusion

PLACEBO COMPARATOR

Saline infusion given subcutaneously for 4 weeks.

Other: Placebo infusion

Very low calorie diet

ACTIVE COMPARATOR

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

Other: Very low calorie diet

Interventions

Roux en Y Gastric Bypass Surgery PROCEDURE

Roux en Y Gastric Bypass

Gut hormone infusion OTHER

Gut hormone infusion

Placebo infusion OTHER

Placebo infusion

Very low calorie diet OTHER

Very low calorie diet

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Imperial College London: lead

Study Sites (1)

NIHR/Wellcome Trust Imperial CRF, Hammersmith Hospital

London, Greater London, United Kingdom

RECRUITING

Related Publications (6)

• Alexiadou K, Cuenco J, Howard J, Wewer Albrechtsen NJ, Ilesanmi I, Kamocka A, Tharakan G, Behary P, Bech PR, Ahmed AR, Purkayastha S, Wheller R, Fleuret M, Holst JJ, Bloom SR, Khoo B, Tan TM. Proglucagon peptide secretion profiles in type 2 diabetes before and after bariatric surgery: 1-year prospective study. BMJ Open Diabetes Res Care. 2020 Mar;8(1):e001076. doi: 10.1136/bmjdrc-2019-001076.

  PMID: 32209584 BACKGROUND

• Ilesanmi I, Tharakan G, Alexiadou K, Behary P, Alessimii H, Bovill-Taylor C, Kenkre J, Choudhury S, Doyle C, Purkayastha S, Miras A, Tsironis C, Chahal H, Bloom SR, Oliver NS, Ahmed AR, Khoo B, Tan TM. Roux-en-Y Gastric Bypass Increases Glycemic Variability and Time in Hypoglycemia in Patients With Obesity and Prediabetes or Type 2 Diabetes: A Prospective Cohort Study. Diabetes Care. 2021 Feb;44(2):614-617. doi: 10.2337/dc20-1609. Epub 2020 Dec 17.

  PMID: 33334806 BACKGROUND

• Behary P, Tharakan G, Alexiadou K, Johnson N, Wewer Albrechtsen NJ, Kenkre J, Cuenco J, Hope D, Anyiam O, Choudhury S, Alessimii H, Poddar A, Minnion J, Doyle C, Frost G, Le Roux C, Purkayastha S, Moorthy K, Dhillo W, Holst JJ, Ahmed AR, Prevost AT, Bloom SR, Tan TM. Combined GLP-1, Oxyntomodulin, and Peptide YY Improves Body Weight and Glycemia in Obesity and Prediabetes/Type 2 Diabetes: A Randomized, Single-Blinded, Placebo-Controlled Study. Diabetes Care. 2019 Aug;42(8):1446-1453. doi: 10.2337/dc19-0449. Epub 2019 Jun 8.

  PMID: 31177183 RESULT

• Behary P, Alessimii H, Miras AD, Tharakan G, Alexiadou K, Aldhwayan MM, Purkayastha S, Moorthy K, Ahmed AR, Bloom SR, Tan TM. Tripeptide gut hormone infusion does not alter food preferences or sweet taste function in volunteers with obesity and prediabetes/diabetes but promotes restraint eating: A secondary analysis of a randomized single-blind placebo-controlled study. Diabetes Obes Metab. 2023 Jun;25(6):1731-1739. doi: 10.1111/dom.15028. Epub 2023 Mar 13.

  PMID: 36811311 DERIVED

• Kowalka AM, Alexiadou K, Cuenco J, Clarke RE, Minnion J, Williams EL, Bech P, Purkayastha S, Ahmed AR, Takats Z, Whitwell HJ, Romero MG, Bloom SR, Camuzeaux S, Lewis MR, Khoo B, Tan TM. The postprandial secretion of peptide YY1-36 and 3-36 in obesity is differentially increased after gastric bypass versus sleeve gastrectomy. Clin Endocrinol (Oxf). 2023 Sep;99(3):272-284. doi: 10.1111/cen.14846. Epub 2022 Nov 28.

  PMID: 36345253 DERIVED

• Jones B, Sands C, Alexiadou K, Minnion J, Tharakan G, Behary P, Ahmed AR, Purkayastha S, Lewis MR, Bloom S, Li JV, Tan TM. The Metabolomic Effects of Tripeptide Gut Hormone Infusion Compared to Roux-en-Y Gastric Bypass and Caloric Restriction. J Clin Endocrinol Metab. 2022 Jan 18;107(2):e767-e782. doi: 10.1210/clinem/dgab608.

  PMID: 34460933 DERIVED

MeSH Terms

Conditions

Obesity; Diabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases

Study Officials

• Stephen R Bloom, FRS FRCP MD

  Imperial College London

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tricia Tan, MBChB MRCP

CONTACT

t.tan@imperial.ac.uk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 16, 2013
• First Posted: September 19, 2013
• Study Start: October 1, 2013
• Primary Completion (Estimated): October 31, 2028
• Study Completion (Estimated): October 31, 2028
• Last Updated: April 20, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)