Gut Hormones and Roux en Y Gastric Bypass

Official title

Do Gut Hormones Mediate the Beneficial Effects of Roux-en-Y Bypass?

Overview

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.

Detailed 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.

Interventions

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

Primary outcome measures

• Weight loss [Time frame: Baseline - 4 weeks]

Secondary outcome measures (1)

• Glycaemia [Time frame: Baseline - 4 weeks]

Eligibility 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Basic science

Study locations

United Kingdom · 1 center

• NIHR/Wellcome Trust Imperial CRF, Hammersmith Hospital — London

Publications

• 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
• 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 PMID 33334806
• 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 Random PMID 31177183
• 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 J PMID 36811311
• 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. Ep PMID 36345253
• 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

Identifiers

NCT: NCT01945840 · MR/K02115X/1

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗