Clinical trial NCT05080205: Effects of Morbid Obesity and Bariatric Surgery on Brain Inflammation, Insulin Resistance and Central Reward System
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
Overall status: UNKNOWN
Phase: NA
Conditions: Obesity, Morbid
Insulin Resistance
Keywords: obesity
insulin resistance
central nervous system inflammation
bariatric surgery
Lead sponsor: Turku University Hospital
Sponsor class: OTHER_GOV
First posted: 2021-10-15
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: 60 subjects undergoing bariatric surgery (either Roux-en-Y gastric bypass or Sleeve gastrectomy) and 30 healthy controls
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion criteria:

Morbidly obese group

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

Non-obese controls

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

Exclusion criteria:

Morbidly obese group

1. Metal objects in the body (including pacemakers, metallic artificial valve prostheses, inner ear implants, surgical clipses, 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.

Non-obese controls

1. Metal objects in the body (including pacemakers, metallic artificial valve prostheses, inner ear implants, surgical clipses, 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

Primary outcomes:
measure: Change in central inflammation
timeFrame: Controls: 0 months; Morbidly obese: preoperatively, 6 months postoperatively
Secondary outcomes:
measure: Changes in central reward system using fMRI imaging
timeFrame: Controls: 0 months; Morbidly obese: preoperatively, 6 months, 12 months, 24 months postoperatively
measure: Changes in brain μ-opioid receptor availability using PET imaging
timeFrame: Controls: 0 months; Morbidly obese: preoperatively, 6 months, 12 months postoperatively
measure: Changes in cognitive function studied with testing
timeFrame: Controls: 0 months; Morbidly obese: preoperatively, 6 months, 12 months, 24 months postoperatively
measure: Changes in whole-body insulin sensitivity usign FDG-PET imaging
timeFrame: Controls: 0 months; Morbidly obese: preoperatively, 6 months postoperatively
measure: Changes in tissue-specific insulin sensitivity using FDG-PET imaging
timeFrame: Controls: 0 months; Morbidly obese: preoperatively
Other outcomes:
Locations:
city: Turku
country: Finland
facility: Turku PET Centre
Study officials:
affiliation: Turku University Hospital
name: Pirjo Nuutila, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: