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MRI Based Study to Assess Brain-gut Axis in Obesity

Not Applicable
Conditions
Obesity
Interventions
Other: Nutritional Drink A
Other: Nutritional Drink B
Registration Number
NCT05437653
Lead Sponsor
University of Nottingham
Brief Summary

The mechanism of neural communication between the brain and gut in the regulation of food intake is complex and not fully understood. Magnetic Resonance Imaging (MRI) is a powerful non-invasive imaging tool that allows studying the function of the brain and gut. The aim of this study is to develop MRI methods to combine brain and gut imaging in a single MRI scan session. The developed techniques will then be used to assess the brain-gut axis to a high fat drink compared with iso-caloric/iso-viscous/iso-volumetric carbohydrate drink in people with obesity and healthy weight participants. The findings could provide a possible explanation for why some people are heavier than others.

Detailed Description

20 healthy weight participant (18 Kg/m2\>BMI\<30Kg/m2) and 20 age- and sex- matched peoples with obesity (BMI \>30 Kg/m2) will be invited to a double-blinded two-way crossover MRI study, approximately 1 week apart, to assess the interplay between brain and gut to food intake.

Brain and gut MRI scans will be collected at fasted/baseline and at different time points postprandial for 120 mins using the 3T Ingenia Philips scanner. Brain measurements including resting state-fMRI, cerebral blood flow (CBF), and task-fMRI scans will be collected. During the task fMRI scan, images of high and low energy food pictures, and non-food control pictures will be presented. Food images are extensively used in fMRI studies to characterise the neural systems involved in processing the hedonic value of food as well as satiety and hunger signals. In addition to brain scans, sequences of gut scans will be collected to assess gastric volume, small bowel water content, and superior mesenteric artery (SMA) responses pre- and post-prandial. Blood samples will be collected to assess gut hormones (CCK, GLP1- PYY, ghrelin) insulin and glucose, triglycerides, free fatty acid levels at different timepoints. In addition, satiety and appetite scores will be collected using visual analogue scales. The total scan time including the fed and break times is around 3 hours.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
40
Inclusion Criteria
  • Aged 18-45, male and female (females will have the study days arranged during the early phase of the menstrual cycle).
  • Body mass index (BMI): normal weight participants ≥ 19 and ≤ 25 Kg/m2, and obese participants > 30 Kg/m2
  • Able to give voluntary written informed consent to participate in the study
  • Able to understand the requirements of the study
  • Apparently healthy: no medical conditions which might affect study measurements (judged by health questionnaire, and blood screening)
Exclusion Criteria
  • Any reported history of neurological or gastrointestinal disorders
  • Any reported history of surgery that could affect gastrointestinal function (e.g. colectomy, small bowel resection)
  • Abnormal screening procedures including depression and eat restriction
  • Laboratory results that are clinically significant, including diabetes, dyslipidemia, pancreatitis, or untreated hypertension.
  • Contraindications for MRI scanning i.e. metallic implants, pacemakers, history of metallic foreign body in eye(s) and penetrating eye injury, assessed by standard MRI safety questionnaire.
  • Under medication (expect aspirin/paracetamol), antibiotic or prescribed probiotic treatment in the past 12 weeks.
  • Following a medically- or self-prescribed diet during the two weeks prior to the pre-study examination and until the end of the study.
  • Reported weight loss or gain ≥ 10 % of bodyweight during the six months period before the pre-study examination
  • Pregnancy or breastfeeding declared by candidate
  • Smoking
  • Left-handed assessed by handedness questionnaire. This is to control for brain's lateralisation effects (activation in one side of the brain) that may show variations between left and right handed participants.
  • Participation in another clinical or research study within the previous 3 months of the study
  • Cannot lie flat or exceeding the scanner bed weight limit of 250 kg.
  • Poor understanding of the spoken and/or written English language

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Obese groupNutritional Drink BObese group
Obese groupNutritional Drink AObese group
Control groupNutritional Drink BHealthy weight group ( same age and sex)
Control groupNutritional Drink AHealthy weight group ( same age and sex)
Primary Outcome Measures
NameTimeMethod
Changes in Cerebral blood flow between drinks (Fat drink VS Carbohydrate drink) and across groups (Healthy weight VS Obese)From baseline to up to 2 hours after ingesting the drinks

Cerebral blood flow differences

Correlations between gut and brain responses to assess alterations in brain-gut axis between drinks (Fat drink VS Carbohydrate drink) and across groups (Healthy weight VS Obese)From baseline to up to 2 hours after ingesting the drinks

Exploratory correlations between brain and gut responses

Changes in appetite- and satiety-related brain responses between drinks ( Fat drink VS Carbohydrate drink) and across groups (Healthy weight VS obese)From baseline to up to 2 hours after ingesting the drinks

Blood oxygen level-dependent (BOLD) responses to high-calorie, low-calorie and non-food images

Changes resting state brain networks between drinks (Fat drink VS Carbohydrate drink) and across groups (Healthy weight VS Obese)From baseline to up to 2 hours after ingesting the drinks

Alterations in functional brain connectivity/networks in brain regions involved in homeostatic and hedonic brain circuits.

Changes in gastric volume between drinks (Fat drink VS Carbohydrate drink) and across groups (Healthy weight VS Obese)From baseline to up to 2 hours after ingesting the drinks

Area Under the Curve of post-prandial gastric volumes, measured by MRI

Secondary Outcome Measures
NameTimeMethod
Changes in satiety and appetite regulators between drinks (Fat drink VS Carbohydrate drink) and across groups (Healthy weight VS Obese)From baseline to up to 2 hours after ingesting the drinks

Area Under the Curve of post-prandial serum gut hormone (CCK, GLP-1, PYY, Ghrelin), insulin, free fatty acid, glucose, and triglyceride concentrations

Changes in satiety and appetite score (VAS) between drinks (Fat drink VS Carbohydrate drink) and across groups (Healthy weight VS Obese)From baseline to up to 2 hours after ingesting the drinks

Area Under the Curve for appetite (Fullness, Hunger, Prospective food consumption) post prandial 100 mm VAS scores AUC2h

Correlations between blood, brain and gut and satiety dateFrom baseline to up to 2 hours after ingesting the drinks

Exploratory correlations between blood, brain and gut responses and satiety data

Changes in small bowel water content between drinks (Fat drink VS Carbohydrate drink) and across groups (Healthy weight VS Obese)From baseline to up to 2 hours after ingesting the drinks

Area Under the Curve of post-prandial small bowel water content, measured by MRI, up to 2h (AUC2h) postprandially

Trial Locations

Locations (1)

University of Nottingham

🇬🇧

Nottingham, United Kingdom

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