Condition category
Nutritional, Metabolic, Endocrine
Date applied
30/06/2010
Date assigned
30/06/2010
Last edited
28/08/2014
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Dr Katharine Hunt

ORCID ID

Contact details

133 Coldharbour Lane
London
SE5 9NU
United Kingdom
katharine.f.hunt@kcl.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

7405

Study information

Scientific title

Acronym

DRN 381 (RYGB)

Study hypothesis

Obesity and related health problems such as Type 2 diabetes are becoming much more common and cause ill health and early death. We do not understand why some people are particularly prone to weight gain and diabetes. One possible explanation is that brain mechanisms controlling food intake are abnormal in people predisposed to obesity and/or diabetes. Roux-en-Y Gastric Bypass (RYGB), a type of surgery for obesity, is effective at causing weight loss. People who have had RYGB exhibit changes in appetite (the drive to eat) and/or satiation (feeling of fullness).

Hypotheses:
Our overarching hypothesis is that brain control of food intake is abnormal in insulin-resistant states, predisposing to obesity and Type 2 diabetes, in a way that is amenable to correction e.g. by RYGB and to increase our understanding of the mechanisms involved. We will examine the following hypotheses:
1. That in people who have had successful RYGB the central (brain) responses to food ingestion are different when the effect of surgery is inhibited (mimicking the pre-operative state) and when it is active (the post-operative state)
2. That the central responses to food ingestion are abnormal in insulin resistance and obesity

Protocol:
We are measuring, in the fasted and fed (post 400 kcal meal) state: regional brain activation using (18F)-fluoro-deoxyglucose positron emission tomography (FDG-PET) brain imaging; gut peptides; and appetite and satiety (using visual analogue scales and an ad-libitum meal).

Study One will be performed in 12 people who have lost weight after RYGB in their normal state and using somatostatin infusion to inhibit the satiety effects of surgery.

Study Two compares responses between three groups of 12 people (who have not had obesity surgery):
1. Normal weight (body mass index [BMI] 20 - 25 kg/m^2)
2. Overweight insulin sensitive (BMI 25 - 40 kg/m^2 and updated homeostatic model assessment [HOMA2-IR] greater than or equal to 0.76)
3. Overweight insulin resistant (BMI 25 - 40 kg/m2 and HOMA2-IR greater than or equal to 1.47)

Ethics approval

MREC approved, ref: 08/H0801/152

Study design

Single-centre observational screening cross-sectional study

Primary study design

Observational

Secondary study design

Cross-section survey

Trial setting

Hospitals

Trial type

Screening

Patient information sheet

Condition

Topic: Diabetes Research Network; Subtopic: Type 2; Disease: Obesity

Intervention

Intravenous somatostatin infusion (to inhibit the satiety effects of RYGB) compared to intravenous saline control (Study One, post RYGB only). Post 400 kcal meal compared to no food intake.

Intervention type

Other

Phase

Not Specified

Drug names

Primary outcome measures

Regional brain activation: regional brain activation using FDG-PET brain imaging

Secondary outcome measures

1. Appetite and satiety using visaul analogue scales and an ad-libitum meal
2. Gut peptides

Overall trial start date

03/06/2009

Overall trial end date

30/09/2011

Reason abandoned

Eligibility

Participant inclusion criteria

1. Aged 18 years or over
2. Able to provide informed consent to participate in the study
3. Able to lie flat in the scanner for duration of scans
4. Right handedness (because of the possibility of lateralisation of cerebral responses)
5. For women of childbearing potential in all groups:
5.1. Using effective form of contraception
5.2. Willing to have a pregnancy test at the start of each scanning visit
5.3. Willing to attend for scanning visits during the first 10 days of their menstrual cycle
6. For STUDY ONE (RYGB):
6.1. Roux-en-Y gastric bypass 3 months to 10 years previously
6.2. BMI 25 - 40 kg/m^2
6.3. Weight loss of more than 10% of excess body weight since surgery
7. For STUDY TWO, Group A (non-overweight, no obesity surgery group):
7.1. No previous obesity surgery
7.2. BMI 20 - 25 kg/m^2
8. For STUDY TWO, Group B (overweight/obese, no obesity surgery with insulin resistance with or without Type 2 diabetes):
8.1. No previous obesity surgery
8.2. BMI 25 - 40 kg/m^2
8.3. HOMA2-IR greater than or equal to 1.47 with or without Type 2 diabetes (managed with diet/exercise/metformin only)
9. For STUDY TWO, Group C (overweight/obese, no obesity surgery, insulin-sensitive group):
9.1. No previous obesity surgery
9.2. BMI 25 - 40 kg/m^2
9.3. HOMA2-IR greater than or equal to 0.76

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned sample size: 48; UK sample size: 48

Participant exclusion criteria

1. Inability to give formal consent
2. Unable to communicate in spoken English (due to the importance of being able to communicate while study subjects are in the scanner)
3. Age less than 18 years
4. Pregnancy, planning pregnancy, or breastfeeding
5. Currently enrolled in other clinical study
6. Left-handedness
7. Taking any glucose-lowering medications (except metformin). Subjects taking metformin will be asked to omit it the day before the Test Meal/OGTT visit and the PET scanning visits because metformin affects gastric emptying and thus may affect nutrient absorption).
8. Advanced retinopathy
9. Any significant brain disorder, e.g. previous significant head injury, epilepsy, cerebrovascular disease
10. Use of psychotropic medication, e.g. antidepressants, antipsychotics
11. Unstable angina, myocardial infarction in the previous year, uncontrolled congestive cardiac failure
12. Chronic kidney disease (Stage 3 - 5)
13. Liver function tests more than three times the upper normal limit
14. Coagulopathy (international normalised ratio [INR] greater than 1.5 or platelets less than 50 x 10^9/L)
15. Anaemia (Hb less than 10 g/dL)
16. Recent history of cancer (less than 5 years)
17. Contraindication to magnetic resonance imaging, e.g. cardiac pacemaker

Recruitment start date

03/06/2009

Recruitment end date

30/09/2011

Locations

Countries of recruitment

United Kingdom

Trial participating centre

133 Coldharbour Lane
London
SE5 9NU
United Kingdom

Sponsor information

Organisation

Kings College London (KCL) (UK)

Sponsor details

Strand
London
WC2R 2LS
United Kingdom

Sponsor type

University/education

Website

http://www.kcl.ac.uk/

Funders

Funder type

Charity

Funder name

Diabetes UK (UK)

Alternative name(s)

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes