Effects of Morbid Obesity and Bariatric Surgery on Brain Inflammation, and Activation of Central Reward System (BARIBRAIN)

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

Background: The investigators have found that obesity and insulin resistance result in significantly increased brain insulin-stimulated glucose uptake, whereas in every other tissue glucose uptake is lower in the obese compared to lean individuals. 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.

Aims: The objective of this study is to investigate whether there is brain inflammation in human obesity, and whether weight loss following bariatric surgery decreases brain inflammation.

Methods: A total of 60 morbidly obese subjects, assigned for Roux-en-Y gastric bypass or 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. The following studies will be performed to patients and healthy subjects: 1) structural MRI and MRS, 2) functional MRI, 3) PET imaging of cerebral inflammation and astrocyte activation using [11C]-PK11195, 4) measurement of whole-body and tissue insulin sensitivity by combining hyperinsulinemic, euglycemic clamp with [18F]-FDG-PET, 5) neuropsychological testing. The study procedures will be repeated for the morbidly obese 6 months postoperatively.

Study Overview

• Status: Active, not recruiting
• Conditions: Morbid Obesity
• Intervention / Treatment: Procedure: Bariatric Surgery (RYGB or LSG)

Detailed Description

This is a prospective study, where subjects for the morbidly obese group (N=60) will be recruited from the patients undergoing bariatric surgery according to normal treatment protocol and the bariatric procedure is decided on clinical data together with the bariatric surgeon and the patient. The morbidly obese patients are studied before and 6 months after bariatric surgery.

Results of obese are compared to results of healthy subjects (N=30), who are studied once.

MRI studies: Brain structural MRI and MRS Structural brain MRI will be performed to obtain anatomical reference. The MR part of a 3T PET-MR system will be used for the study . MR spectroscopy (MRS) will be used to determine levels of different metabolites.Brain activation studies (functional MRI) The aim of the fMRI is to assess how morbid obesity and weight loss influence the brain reward system in response to visual cues (not food related); resting state fMRI will also be performed.

Brain inflammation: [¹¹C]-PK11195 tracer with PET/CT is used to determine activation of glial cells, or inflammation, in the brain. After intravenous injection of 500 MBq [¹¹C]-PK11195, a 60-minute dynamic scan on the brain using the same PET/CT cameras will be performed. Both ROI- and SPM based statistics will be used in the statistical analyses.

Whole-body scan with [18F]-FDG and PET/CT during euglycemic hyperinsulinemia used to promote tissue glucose uptake and measure insulin sensitivity. After 60 minutes from the start of clamp, the subjects will be injected intravenously with 150 MBq of [18F]-fluorodeoxyglucose ([18F]-FDG) Thereafter [18F]-fluorodeoxyglucose uptake in the brain, abdomen, femoral region will be measured.

• Study Type: Interventional
• Enrollment (Anticipated): 90
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Finland
  • Turku, Finland, 20520
    • Turku University Hospital
  • Turku, Finland, 20520
    • Turku PET Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 58 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

For the morbidly obese subjects:

1. BMI 35.0-45.0 kg/m2, or BMI 32.0-45.0 kg/m2 and diagnosed diabetes
2. Eligible to bariatric surgery evaluated according to normal treatment paradigm

Exclusion Criteria:

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

For the lean control subjects:

Inclusion Criteria:

1. BMI 18-27 kg/m2
2. Fasting plasma glucose ≤6.1 mmol/L
3. Normal values in 2-hour oral glucose tolerance test

Exclusion Criteria:

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Bariatric surgery; The effect of bariatric surgery (RYGB or LSG) on central inflammation	Procedure: Bariatric Surgery (RYGB or LSG); Morbidly obese subjects will receive either RYGB or LSG, and the effect of bariatric surgery-induced weight loss on brain inflammation will be assessed
No Intervention: No intervention; Healthy lean volunteers

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Obese have brain inflammation compared to healthy ones	Brain PET-[11C]-PK11195 imaging study of obese and healthy lean ones	Both groups at baseline
Bariatric surgery decreases brain inflammation in obesity	PK11195 imaging results are compared before and 6 months after bariatric surgery in obese group studied before and after bariatric surgery	Baseline and 6 months after operation (obese group only)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tissue-specific and whole-body insulin sensitivity are decreased in obese	Glucose uptakes are measured using PET imaging in obese and leans	Baseline obese and leans
Tissue-specific and whole-body glucose improves after bariatric surgery	Comparison before and 6 months after surgery (obese group)	PET imaging studies at baseline and 6 months after operation
Brain neural activity decreased in obesity	Comparison between obese and lean ones using fMRI	Baseline obese and leans
Brain neural activity improves after bariatric surgery	Comparison between obese baseline and 6 months after operation	Baseline and 6 months after operation (obese group)
Brain metabolite concentrations are different in obese	MRS studies for obese and lean ones at baseline are compared	Baseline obese and leans
Brain metabolite concentrations normalize after bariatric surgery	MRS studies for obese before and 6 months postop compared	Baseline and 6 months postop (obese group)

Collaborators and Investigators

• Sponsor: Turku University Hospital
• Investigators: Principal Investigator: Pirjo Nuutila, MD, PhD, Turku UH

Study record dates

Study Major Dates

• Study Start (Actual): February 11, 2019
• Primary Completion (Anticipated): September 1, 2022
• Study Completion (Anticipated): September 1, 2022

Study Registration Dates

• First Submitted: October 7, 2019
• First Submitted That Met QC Criteria: April 10, 2020
• First Posted (Actual): April 13, 2020

Study Record Updates

• Last Update Posted (Actual): October 13, 2021
• Last Update Submitted That Met QC Criteria: October 12, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: magnetic resonance imaging; bariatric surgery; positron emission tomography; euglycaemic hyperinsulinemic clamp; astrogliosis; central inflammation
• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Infections; Overnutrition; Nutrition Disorders; Overweight; Body Weight; Central Nervous System Infections; Obesity; Encephalitis; Inflammation; Obesity, Morbid; Infectious Encephalitis
• Other Study ID Numbers: T26/2019

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No