BariBrainPET: Effects of Morbid Obesity and Bariatric Surgery on Brain Inflammation, Insulin Resistance and Central Reward System

Sponsor

Turku University Hospital (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT05080205

Collaborator

(none)

Enrollment

Location

Arms

45.6

Anticipated Duration (Months)

0.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Background: Morbid obesity is associated with decreased brain µ-opioid receptor availability, possibly resulting in higher food intake needed to gain pleasure from eating. This decrease seems to normalize already 6 months after bariatric surgery, but the longer-term effects have not been studied. Obesity and insulin resistance result in significantly increased brain insulin-stimulated glucose uptake, whereas in every other tissue glucose uptake is lower. One possible explanation to this could be central inflammation and activation of brain glial cells, which has been shown to occur in animal models of obesity. Obesity has also been shown to associate with increased risk of Alzheimer's disease and cognitive decline in several studies.

Aims: The first objective of this study is to both study the effects of bariatric surgery as well as compare the effects of gastric bypass and sleeve gastrectomy on food-associated pleasure, extending the follow-up period to 2 years postoperatively. The second aim is to investigate the effect of morbid obesity and weight loss on brain inflammation and gliosis and its association with increased brain insulin-stimulated glucose uptake. Furthermore, association of obesity, insulin resistance, central inflammation and neurocognitive dysfunction are evaluated.

Condition or Disease	Intervention/Treatment	Phase
Obesity, Morbid Insulin Resistance	Procedure: Bariatric surgery	N/A

Detailed Description

Methods: A total of 60 morbidly obese subjects, 30 assigned for Roux-en-Y gastric bypass and 30 for sleeve gastrectomy according to routine treatment protocols will be recruited for this study. A control group of 30 healthy subjects will also be recruited. We will perform 1) structural MRI and MRS, 2) functional MRI during tasting and visual food cues, 3) PET imaging of µ-opioid receptor availability using [11C]-carfentanil, 4) PET imaging of cerebral inflammation and astrocyte activation using [11C]-PK11195, 5) measurement of whole-body and tissue insulin sensitivity by combining hyperinsulinemic, euglycemic clamp with [18F]-FDG-PET, 6) neuropsychological testing. The control group will only be studied once, whereas study procedures will be repeated for the morbidly obese before very-low calorie diet and 6, 12 and 24 months postoperatively.

Study Design

Study Type:

Interventional

Actual Enrollment :

30 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Intervention Model Description:

60 subjects undergoing bariatric surgery (either Roux-en-Y gastric bypass or Sleeve gastrectomy) and 30 healthy controls60 subjects undergoing bariatric surgery (either Roux-en-Y gastric bypass or Sleeve gastrectomy) and 30 healthy controls

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Effects of Morbid Obesity and Bariatric Surgery on Brain Inflammation, Insulin Resistance and Activation of Central Reward System Studied Using PET- and MRI-imaging

Actual Study Start Date :

Feb 11, 2019

Actual Primary Completion Date :

Oct 10, 2021

Anticipated Study Completion Date :

Dec 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Morbidly obese subjects Bariatric surgery (Roux-en-Y gastric bypass or sleeve gastrectomy)	Procedure: Bariatric surgery Roux-en-Y gastric bypass or sleeve gastrectomy, chosen based on routine evaluation process Other Names: Roux-en-Y gastric bypass Sleeve gastrectomy
No Intervention: Control subjects Non-obese controls are only studied at baseline

Arm

Intervention/Treatment

Experimental: Morbidly obese subjects

Bariatric surgery (Roux-en-Y gastric bypass or sleeve gastrectomy)

Procedure: Bariatric surgery

Roux-en-Y gastric bypass or sleeve gastrectomy, chosen based on routine evaluation process

Other Names:

Roux-en-Y gastric bypass

Sleeve gastrectomy

No Intervention: Control subjects

Non-obese controls are only studied at baseline

Outcome Measures

Primary Outcome Measures

Change in central inflammation [Controls: 0 months; Morbidly obese: preoperatively, 6 months postoperatively]
Assessment of brain glial cell activation using [11C]-PK11195 tracer and positron emission tomography

Secondary Outcome Measures

Changes in central reward system using fMRI imaging [Controls: 0 months; Morbidly obese: preoperatively, 6 months, 12 months, 24 months postoperatively]
Assessment of brain reward system activation after visual/taste cues using functional MRI
Changes in brain μ-opioid receptor availability using PET imaging [Controls: 0 months; Morbidly obese: preoperatively, 6 months, 12 months postoperatively]
Assessment of brain μ-opioid receptor availability using [11C]-carfentanil tracer and positron emission tomography
Changes in cognitive function studied with testing [Controls: 0 months; Morbidly obese: preoperatively, 6 months, 12 months, 24 months postoperatively]
Neuropsychological testing focusing on memory, decision-making and inhibition
Changes in whole-body insulin sensitivity usign FDG-PET imaging [Controls: 0 months; Morbidly obese: preoperatively, 6 months postoperatively]
Assessment of whole-body insulin sensitivity using hyperinsulinemic, euglycemic clamp
Changes in tissue-specific insulin sensitivity using FDG-PET imaging [Controls: 0 months; Morbidly obese: preoperatively]
Assessment of insulin-stimulated glucose uptake in the brain, liver, skeletal muscle and adipose tissue by performing positron emission tomography with [18F]-fluorodeoxyglucose tracer during hyperinsulinemic, euglycemic clamp

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion criteria:

Morbidly obese group

BMI 35.0-45.0 kg/m2, or BMI 32.0-45.0 kg/m2 and diagnosed diabetes
Age 18-60 years
Eligible to bariatric surgery evaluated according to normal treatment paradigm

Non-obese controls

BMI 18-27 kg/m2
Age 18-60 years
Fasting plasma glucose ≤6.1 mmol/L
Normal values in 2-hour oral glucose tolerance test

Exclusion criteria:

Morbidly obese group

Metal objects in the body (including pacemakers, metallic artificial valve prostheses, inner ear implants, surgical clipses, braces, foreign fragments)
Previous participation in PET studies
Pregnancy
Poor compliance, alcohol or drug abuse
Weight over 150 kg or waist circumference over 150 cm
Diabetes with fasting glucose levels ≥7.0 mmol/L, or treatment with insulin
Any chronic disease, medication or condition that could create a hazard to subject safety, endanger study procedures or interfere with the interpretation of results.

Non-obese controls

Metal objects in the body (including pacemakers, metallic artificial valve prostheses, inner ear implants, surgical clipses, braces, foreign fragments)
Previous participation in PET studies
Pregnancy
Poor compliance, alcohol or drug abuse
Smoking
History of eating disorders, drastic weight-gain or weight-loss
History of psychiatric disorders
Any chronic disease, medication or condition that could create a hazard to subject safety, endanger study procedures or interfere with the interpretation of results