CClinicalTrials.gg
Status unknownNCT05080205BariBrainPETUpdated Oct 15, 2021

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

An interventional study of Bariatric surgery in Obesity, Morbid and Insulin Resistance, sponsored by Turku University Hospital. Status unknown at 1 site in Finland. Open to participants aged 18 Years to 60 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2021-10-15.

Sponsored by Turku University Hospital · Not applicable, Interventional, and Treatment

The sponsor has not verified this record recently (last verified Oct 2021), so the status shown — last known as Active, not recruiting — may be out of date.
Phase
Not applicable
Study type
Interventional
Enrollment
30
Allocation
Non-randomized
Ages
18 Years to 60 Years
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Obesity, Morbid
  • Insulin Resistance

Keywords

  • obesity
  • insulin resistance
  • central nervous system inflammation
  • bariatric surgery
03

Who can participate

Ages eligible
18 Years to 60 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

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

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
04

Study design

Phase
Not applicable
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Single group
Masking
None (open label)
Enrollment
30 participants (actual)

Study arms

  • Experimental
    Morbidly obese subjects

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

    Procedure: Bariatric surgery

  • No intervention
    Control subjects

    Non-obese controls are only studied at baseline

Interventions

  • ProcedureBariatric surgery

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

    Also known as: Roux-en-Y gastric bypass, Sleeve gastrectomy

05

What researchers measure

Primary outcomes

  1. Change in central inflammation

    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 outcomes

  1. Changes in central reward system using fMRI imaging

    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

  2. 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

    Time frame: Controls: 0 months; Morbidly obese: preoperatively, 6 months, 12 months postoperatively

  3. Changes in cognitive function studied with testing

    Neuropsychological testing focusing on memory, decision-making and inhibition

    Time frame: Controls: 0 months; Morbidly obese: preoperatively, 6 months, 12 months, 24 months postoperatively

  4. Changes in whole-body insulin sensitivity usign FDG-PET imaging

    Assessment of whole-body insulin sensitivity using hyperinsulinemic, euglycemic clamp

    Time frame: Controls: 0 months; Morbidly obese: preoperatively, 6 months postoperatively

  5. 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

    Time frame: Controls: 0 months; Morbidly obese: preoperatively

06

Study locations

1 site
  • Turku PET Centre
    Turku, 20520, Finland
07

References and documents

Individual participant data

Plan to share: Yes — Under preparation.

Supporting information: Study protocol, Sap, Icf, Csr

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT05080205
Lead sponsor
Turku University Hospital
Responsible party
Pirjo Nuutila (professor, Turku University Hospital) — Principal investigator
First posted
Oct 15, 2021
Start date
Feb 11, 2019
Primary completion
Oct 10, 2021
Completion
Dec 2022 (estimated)
Last update
Oct 15, 2021

Study contacts

Pirjo Nuutila, MD, PhD
principal investigator · Turku University Hospital

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
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