Back to resultsEffects of Morbid Obesity and Bariatric Surgery on Brain Inflammation, Insulin Resistance and Central Reward System (BariBrainPET)
Primary Purpose
Obesity, Morbid, Insulin Resistance
Status
Unknown status
Phase
Not Applicable
Locations
Finland
Study Type
Interventional
Intervention
Bariatric surgery
Sponsored by
About this trial
This is an interventional treatment trial for Obesity, Morbid focused on measuring obesity, insulin resistance, central nervous system inflammation, bariatric surgery
Eligibility Criteria
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
Sites / Locations
- Turku PET Centre
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
No Intervention
Arm Label
Morbidly obese subjects
Control subjects
Arm Description
Bariatric surgery (Roux-en-Y gastric bypass or sleeve gastrectomy)
Non-obese controls are only studied at baseline
Outcomes
Primary Outcome Measures
Change in central inflammation
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
Assessment of brain reward system activation after visual/taste cues using functional MRI
Changes in brain μ-opioid receptor availability using PET imaging
Assessment of brain μ-opioid receptor availability using [11C]-carfentanil tracer and positron emission tomography
Changes in cognitive function studied with testing
Neuropsychological testing focusing on memory, decision-making and inhibition
Changes in whole-body insulin sensitivity usign FDG-PET imaging
Assessment of whole-body insulin sensitivity using hyperinsulinemic, euglycemic clamp
Changes in tissue-specific insulin sensitivity using FDG-PET imaging
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
Full Information
NCT ID
NCT05080205
First Posted
June 6, 2018
Last Updated
October 12, 2021
Sponsor
Turku University Hospital
1. Study Identification
Unique Protocol Identification Number
NCT05080205
Brief Title
Effects of Morbid Obesity and Bariatric Surgery on Brain Inflammation, Insulin Resistance and Central Reward System
Acronym
BariBrainPET
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
Study Type
Interventional
2. Study Status
Record Verification Date
October 2021
Overall Recruitment Status
Unknown status
Study Start Date
February 11, 2019 (Actual)
Primary Completion Date
October 10, 2021 (Actual)
Study Completion Date
December 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Turku University Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Obesity, Morbid, Insulin Resistance
Keywords
obesity, insulin resistance, central nervous system inflammation, bariatric surgery
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Model Description
60 subjects undergoing bariatric surgery (either Roux-en-Y gastric bypass or Sleeve gastrectomy) and 30 healthy controls
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
30 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Morbidly obese subjects
Arm Type
Experimental
Arm Description
Bariatric surgery (Roux-en-Y gastric bypass or sleeve gastrectomy)
Arm Title
Control subjects
Arm Type
No Intervention
Arm Description
Non-obese controls are only studied at baseline
Intervention Type
Procedure
Intervention Name(s)
Bariatric surgery
Other Intervention Name(s)
Roux-en-Y gastric bypass, Sleeve gastrectomy
Intervention Description
Roux-en-Y gastric bypass or sleeve gastrectomy, chosen based on routine evaluation process
Primary Outcome Measure Information:
Title
Change in central inflammation
Description
Assessment of brain glial cell activation using [11C]-PK11195 tracer and positron emission tomography
Time Frame
Controls: 0 months; Morbidly obese: preoperatively, 6 months postoperatively
Secondary Outcome Measure Information:
Title
Changes in central reward system using fMRI imaging
Description
Assessment of brain reward system activation after visual/taste cues using functional MRI
Time Frame
Controls: 0 months; Morbidly obese: preoperatively, 6 months, 12 months, 24 months postoperatively
Title
Changes in brain μ-opioid receptor availability using PET imaging
Description
Assessment of brain μ-opioid receptor availability using [11C]-carfentanil tracer and positron emission tomography
Time Frame
Controls: 0 months; Morbidly obese: preoperatively, 6 months, 12 months postoperatively
Title
Changes in cognitive function studied with testing
Description
Neuropsychological testing focusing on memory, decision-making and inhibition
Time Frame
Controls: 0 months; Morbidly obese: preoperatively, 6 months, 12 months, 24 months postoperatively
Title
Changes in whole-body insulin sensitivity usign FDG-PET imaging
Description
Assessment of whole-body insulin sensitivity using hyperinsulinemic, euglycemic clamp
Time Frame
Controls: 0 months; Morbidly obese: preoperatively, 6 months postoperatively
Title
Changes in tissue-specific insulin sensitivity using FDG-PET imaging
Description
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
Time Frame
Controls: 0 months; Morbidly obese: preoperatively
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pirjo Nuutila, MD, PhD
Organizational Affiliation
Turku University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Turku PET Centre
City
Turku
ZIP/Postal Code
20520
Country
Finland
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Under preparation.
Learn more about this trial
Effects of Morbid Obesity and Bariatric Surgery on Brain Inflammation, Insulin Resistance and Central Reward System
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