The Poor Responders Study

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

Why do Some Patients Respond Better Than Others to Bariatric Surgery?

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05404061
• Other study ID #: 17/LO/1323
• Status: Recruiting
• Phase: N/A
• Start date: August 1, 2018
• Est. completion date: September 1, 2027

Study information

• Verified date: September 2023
• Source: Imperial College London
• Contact: Kleopatra Alexiadou, PhD
• Phone: +442033138038
• Email: k.alexiadou[@]imperial.ac.uk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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. Good responders: this is the majority of patients who lose the expected amount of weight based on the published studies.

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.

The so-called "poor responders" are exposed to all the risks of the operation and do not benefit from the weight loss as much as good responders.

This study would therefore like to investigate the physiological factors that distinguish poor from good responders before, and after bariatric surgery. The study team hypothesizes that compared to good responders, poor responders exhibit:

1. a smaller degree of fullness sensation after a meal,

2. a lower energy expenditure after a meal, and

3. genetic changes (single nucleotide polymorphisms) that predispose the poor responder to development of obesity.

In addition, the study team hypothesizes that poor responders exhibit:

1. lower gut hormone secretion after a meal and

2. 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 220
• Est. completion date: September 1, 2027
• Est. primary completion date: September 1, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• 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.

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.

• 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)

Related Conditions & MeSH terms

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

Intervention

Other:
• Gut hormones
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: 0.9% saline, GLP-1

Locations

Country	Name	City	State
United Kingdom	Imperial College London	London

Sponsors (1)

Lead Sponsor	Collaborator
Imperial College London

Country where clinical trial is conducted

United Kingdom, 

References & 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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.
Primary	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.
Primary	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	Change in Resting Energy Expenditure	Resting energy expenditure assessment via indirect calorimetry.	Change between two visits: before and 1 year after bariatric surgery (Prospective assessment of gut hormone response pre and post-surgery).
Secondary	Change in Diet Induced Thermogenesis	Diet induced thermogenesis assessment via indirect calorimetry.	Change between two visits: before and 1 year after bariatric surgery (Prospective assessment of gut hormone response pre and post-surgery).
Secondary	Change in Genetic factors	Change in genetic factors assessed by collection of plasma DNA samples.	Change between two visits: Before and 1 year after bariatric surgery.