Effects of Morbid Obesity and Bariatric Surgery on Brain Inflammation, Insulin Resistance and Central Reward System (BariBrainPET)
12 oktober 2021 uppdaterad av: Pirjo Nuutila, Turku University Hospital
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: 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.
Studieöversikt
Status
Aktiv, inte rekryterande
Betingelser
Intervention / Behandling
Detaljerad beskrivning
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.
Studietyp
Interventionell
Inskrivning (Faktisk)
30
Fas
- Inte tillämpbar
Kontakter och platser
Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.
Studieorter
-
-
-
Turku, Finland, 20520
- Turku PET Centre
-
-
Deltagandekriterier
Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.
Urvalskriterier
Åldrar som är berättigade till studier
18 år till 60 år (Vuxen)
Tar emot friska volontärer
Nej
Kön som är behöriga för studier
Allt
Beskrivning
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
Studieplan
Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.
Hur är studien utformad?
Designdetaljer
- Primärt syfte: Behandling
- Tilldelning: Icke-randomiserad
- Interventionsmodell: Enskild gruppuppgift
- Maskning: Ingen (Open Label)
Vapen och interventioner
Deltagargrupp / Arm |
Intervention / Behandling |
|---|---|
|
Experimentell: Morbidly obese subjects
Bariatric surgery (Roux-en-Y gastric bypass or sleeve gastrectomy)
|
Roux-en-Y gastric bypass or sleeve gastrectomy, chosen based on routine evaluation process
Andra namn:
|
|
Inget ingripande: Control subjects
Non-obese controls are only studied at baseline
|
Vad mäter studien?
Primära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
|
Change in central inflammation
Tidsram: Controls: 0 months; Morbidly obese: preoperatively, 6 months postoperatively
|
Assessment of brain glial cell activation using [11C]-PK11195 tracer and positron emission tomography
|
Controls: 0 months; Morbidly obese: preoperatively, 6 months postoperatively
|
Sekundära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
|
Changes in central reward system using fMRI imaging
Tidsram: 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
|
Controls: 0 months; Morbidly obese: preoperatively, 6 months, 12 months, 24 months postoperatively
|
|
Changes in brain μ-opioid receptor availability using PET imaging
Tidsram: 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
|
Controls: 0 months; Morbidly obese: preoperatively, 6 months, 12 months postoperatively
|
|
Changes in cognitive function studied with testing
Tidsram: Controls: 0 months; Morbidly obese: preoperatively, 6 months, 12 months, 24 months postoperatively
|
Neuropsychological testing focusing on memory, decision-making and inhibition
|
Controls: 0 months; Morbidly obese: preoperatively, 6 months, 12 months, 24 months postoperatively
|
|
Changes in whole-body insulin sensitivity usign FDG-PET imaging
Tidsram: Controls: 0 months; Morbidly obese: preoperatively, 6 months postoperatively
|
Assessment of whole-body insulin sensitivity using hyperinsulinemic, euglycemic clamp
|
Controls: 0 months; Morbidly obese: preoperatively, 6 months postoperatively
|
|
Changes in tissue-specific insulin sensitivity using FDG-PET imaging
Tidsram: 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
|
Controls: 0 months; Morbidly obese: preoperatively
|
Samarbetspartners och utredare
Det är här du hittar personer och organisationer som är involverade i denna studie.
Sponsor
Utredare
- Huvudutredare: Pirjo Nuutila, MD, PhD, Turku University Hospital
Studieavstämningsdatum
Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.
Studera stora datum
Studiestart (Faktisk)
11 februari 2019
Primärt slutförande (Faktisk)
10 oktober 2021
Avslutad studie (Förväntat)
1 december 2022
Studieregistreringsdatum
Först inskickad
6 juni 2018
Först inskickad som uppfyllde QC-kriterierna
12 oktober 2021
Första postat (Faktisk)
15 oktober 2021
Uppdateringar av studier
Senaste uppdatering publicerad (Faktisk)
15 oktober 2021
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
12 oktober 2021
Senast verifierad
1 oktober 2021
Mer information
Termer relaterade till denna studie
Ytterligare relevanta MeSH-villkor
- Patologiska processer
- Störningar i glukosmetabolism
- Metaboliska sjukdomar
- Hjärnsjukdomar
- Sjukdomar i centrala nervsystemet
- Sjukdomar i nervsystemet
- Infektioner
- Övernäring
- Näringsstörningar
- Övervikt
- Kroppsvikt
- Infektioner i centrala nervsystemet
- Hyperinsulinism
- Fetma
- Encefalit
- Inflammation
- Insulinresistens
- Fetma, sjuklig
- Infektiös encefalit
Andra studie-ID-nummer
- BariBrain-PET
- T153/2018 (Annan identifierare: The Hospital District of Southwest Finland)
Plan för individuella deltagardata (IPD)
Planerar du att dela individuella deltagardata (IPD)?
Ja
IPD-planbeskrivning
Under preparation.
IPD-delning som stöder informationstyp
- Studieprotokoll
- Statistisk analysplan (SAP)
- Informerat samtycke (ICF)
- Klinisk studierapport (CSR)
Läkemedels- och apparatinformation, studiedokument
Studerar en amerikansk FDA-reglerad läkemedelsprodukt
Nej
Studerar en amerikansk FDA-reglerad produktprodukt
Nej
Denna information hämtades direkt från webbplatsen clinicaltrials.gov utan några ändringar. Om du har några önskemål om att ändra, ta bort eller uppdatera dina studieuppgifter, vänligen kontakta register@clinicaltrials.gov. Så snart en ändring har implementerats på clinicaltrials.gov, kommer denna att uppdateras automatiskt även på vår webbplats .