The Poor Responders Study

NCT05404061 | Recruiting

• 1 other identifier: 17/LO/1323
• Study Type: interventional
• Target: 220
• Locations: 1 country
• Sites: 1

Brief Summary

Obesity and type 2 diabetes are major causes of illness and premature death worldwide and their incidence is increasing rapidly. Bariatric surgery is considered as the "gold-standard" surgical treatment for both conditions. However, not all patients do equally well after surgery and indeed the weight loss experienced by patients undergoing bariatric surgery can vary. As such when patients are seen after bariatric surgery in clinic they fall in one of the following two categories:

1. 1.Good responders: this is the majority of patients who lose the expected amount of weight based on the published studies.
2. 2.Poor responders: this is a small group of patients who either lose less than the expected amount of weight after bariatric surgery or lose the expected amounts of weight early after surgery but then regain a substantial proportion of the weight they have lost.
3. 3.a smaller degree of fullness sensation after a meal,
4. 4.a lower energy expenditure after a meal, and
5. 5.genetic changes (single nucleotide polymorphisms) that predispose the poor responder to development of obesity.
6. 6.lower gut hormone secretion after a meal and
7. 7.are less sensitive to the physiological action of gut hormones compared to good responders and that this difference in gut hormone secretion and response to gut hormones prior to bariatric surgery can be helpful to predict response to bariatric surgery.

Conditions

Bariatric Surgery Candidate; Obesity, Morbid; Diabetes Mellitus, Type 2

Outcome Measures

Primary Outcomes (3)

• Gut hormone secretion study: Peak plasma level of gut hormones after meal ingestion

  A standardized mixed-meal tolerance test. Blood samples will be taken at intervals over four hours. These will be analysed for gut hormones.

  During one study visit (Mixed Meal Test), at least 1 year post-surgery.

• Gut hormone sensitivity study: Change in Food intake following gut hormone infusion compared to placebo.

  Ad libitum meal test. A meal will be served to participants and they will be allowed 20 minutes to eat until they feel comfortably full. Food intake will be measured at the end of the meal.

  During three study visits (gut hormone infusion visits), at least 1 year post-surgery.

• Prospective assessment of gut hormone response pre and post-surgery: Change in Peak plasma level of gut hormones after meal ingestion.

  A standardized mixed-meal tolerance test. Blood samples will be taken at intervals over four hours. These will be analysed for gut hormones.

  During two study visits (Mixed Meal Test), one before and one 1 year after surgery.

Secondary Outcomes (3)

• Change in Resting Energy Expenditure

  Change between two visits: before and 1 year after bariatric surgery (Prospective assessment of gut hormone response pre and post-surgery).

• Change in Diet Induced Thermogenesis

  Change between two visits: before and 1 year after bariatric surgery (Prospective assessment of gut hormone response pre and post-surgery).

• Change in Genetic factors

  Change between two visits: Before and 1 year after bariatric surgery.

Study Arms (3)

Gut hormone secretion study

NO INTERVENTION

This will be a retrospective study of participants who have undergone bariatric surgery. On the day of the visit participants will undergo comprehensive physiological profiling which will include the following tests: * Body weight and bioelectrical impedance analysis * Mixed Meal Tolerance Test. This will be analysed for metabolites including gut hormones, insulin, glucose, bile acids and their sub-fractions, fibroblast-growth factors, lipids and immune profiles. * Resting Energy Expenditure and Diet Induced Thermogenesis assessed via Indirect Calorimetry * Metabolomic and Metagenomic Assessment

Gut hormone sensitivity study

PLACEBO COMPARATOR

This will be a single blinded study with participants attending three visits. Their first visit will act as an acclimatisation visit and participants will be infused subcutaneously with a triple gut hormone infusion (GLP-1, PYY and OXM). This will not only allow us to acclimatise the study volunteer to the study visits, but also allow us to test for subject tolerability of the gut hormones. Occasionally some volunteers are more sensitive to the gut hormone infusion and the doses needs to be titrated down. The doses used will be established doses of the gut hormones infused previously and which have been shown to be safe and tolerated, and to reduce appetite (In house data).

Other: Gut hormones

Prospective assessment of gut hormone response pre and post-surgery

NO INTERVENTION

This will be a prospective study assessing the gut hormone response pre and post bariatric surgery. On the day of the visit participants will undergo comprehensive physiological profiling which will include the following tests: * Body weight and bioelectrical impedance analysis * Mixed Meal Tolerance Test. This will be analysed for metabolites including gut hormones, insulin, glucose, bile acids and their sub-fractions, fibroblast-growth factors, lipids and immune profiles. * Resting Energy Expenditure and Diet Induced Thermogenesis assessed via Indirect Calorimetry * Metabolomic and Metagenomic Assessment

Interventions

Gut hormones OTHER

Their first visit will act as an acclimatisation visit and participants will be infused subcutaneously with a triple gut hormone infusion (GLP-1, PYY and OXM). This will not only allow us to acclimatise the study volunteer to the study visits, but also allow us to test for subject tolerability of the gut hormones. For the next two visits participants will be randomised in a single-blinded fashion to a subcutaneous infusion of either: 1. 0.9% saline, 2. GLP-1

Gut hormone sensitivity study

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 18 -70 years.
• Male or female.
• Previous bariatric surgery for obesity and/or diabetes (studies 1 and 2).
• ≥1 year interval after bariatric surgery (studies 1 and 2).
• Awaiting bariatric surgery at the Imperial Weight Centre (study 3)
• Able to give informed consent.

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.
• 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.
• Any other co-morbidity that would compromise the validity of the study or the safety of the participant such as heart failure or clinically apparent cardiovascular disease.
• Anatomical or endocrinological pathology causing poor weight loss or weight regain
• Uncontrolled hypertension (systolic blood pressure of 160 mmHg or above and/or diastolic blood pressure of 100 mmHg or above)
• Participation in a research study within the last two months.
• Unable to speak English (this is relevant to answering the psychological questionnaires)

Sponsors & Collaborators

• Imperial College London: lead

Study Sites (1)

Imperial College London

London, W120NN, United Kingdom

RECRUITING

Related Publications (5)

• Aasheim ET, Aylwin SJ, Radhakrishnan ST, Sood AS, Jovanovic A, Olbers T, le Roux CW. Assessment of obesity beyond body mass index to determine benefit of treatment. Clin Obes. 2011 Apr;1(2-3):77-84. doi: 10.1111/j.1758-8111.2011.00017.x. Epub 2011 Jul 5.

  PMID: 25585572 BACKGROUND

• Batterham RL, Cowley MA, Small CJ, Herzog H, Cohen MA, Dakin CL, Wren AM, Brynes AE, Low MJ, Ghatei MA, Cone RD, Bloom SR. Gut hormone PYY(3-36) physiologically inhibits food intake. Nature. 2002 Aug 8;418(6898):650-4. doi: 10.1038/nature00887.

  PMID: 12167864 BACKGROUND

• De Silva A, Salem V, Long CJ, Makwana A, Newbould RD, Rabiner EA, Ghatei MA, Bloom SR, Matthews PM, Beaver JD, Dhillo WS. The gut hormones PYY 3-36 and GLP-1 7-36 amide reduce food intake and modulate brain activity in appetite centers in humans. Cell Metab. 2011 Nov 2;14(5):700-6. doi: 10.1016/j.cmet.2011.09.010. Epub 2011 Oct 13.

  PMID: 22000927 BACKGROUND

• Laferrere B, Swerdlow N, Bawa B, Arias S, Bose M, Olivan B, Teixeira J, McGinty J, Rother KI. Rise of oxyntomodulin in response to oral glucose after gastric bypass surgery in patients with type 2 diabetes. J Clin Endocrinol Metab. 2010 Aug;95(8):4072-6. doi: 10.1210/jc.2009-2767. Epub 2010 May 25.

  PMID: 20501690 BACKGROUND

• Tan TM, Field BC, McCullough KA, Troke RC, Chambers ES, Salem V, Gonzalez Maffe J, Baynes KC, De Silva A, Viardot A, Alsafi A, Frost GS, Ghatei MA, Bloom SR. Coadministration of glucagon-like peptide-1 during glucagon infusion in humans results in increased energy expenditure and amelioration of hyperglycemia. Diabetes. 2013 Apr;62(4):1131-8. doi: 10.2337/db12-0797. Epub 2012 Dec 17.

  PMID: 23248172 BACKGROUND

MeSH Terms

Conditions

Obesity, Morbid; Diabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

Obesity; 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

• Tricia M Tan, PhD

  Imperial College London

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kleopatra Alexiadou, PhD

CONTACT

+442033138038; k.alexiadou@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: March 8, 2022
• First Posted: June 3, 2022
• Study Start: August 1, 2018
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2027
• Last Updated: May 9, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)