Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 30 of 54 for:    Recruiting, Not yet recruiting, Available Studies | NOT (Use Disorders OR Marijuana Use OR Dependence OR Abuse OR Drug Use) | cannabinoids

Neuromolecular Risk Factors for Obesity (PROSPECT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03106688
Recruitment Status : Recruiting
First Posted : April 10, 2017
Last Update Posted : May 1, 2017
Sponsor:
Information provided by (Responsible Party):
Pirjo Nuutila, Turku University Hospital

Brief Summary:
The goal of this project is to characterize the neural and psychological mechanisms that contribute to development of obesity in the early adulthood. We address the neuromolecular risk factors for obesity using multi-modal molecular (positron emission tomography with) and functional (functional magnetic resonance imaging) neuroimaging in a prospective design. Normal weight adolescents with high versus low familial, genetic and psychological risk factors for obesity will be studied and followed for five years.

Condition or disease Intervention/treatment Phase
Obesity Diagnostic Test: fMRI imaging Diagnostic Test: [11C]carfentanil PET scan Diagnostic Test: [18F]FMPEP-d2 PET scan Diagnostic Test: [18F]-FDG PET scan Diagnostic Test: Physical activity measures and fitness tests Diagnostic Test: Laboratory measurements Diagnostic Test: Questionnaires Diagnostic Test: Hyperinsulinemic euglycemic clamp Not Applicable

Detailed Description:

Diet, nutrition, and physical exercise are critical factors in the maintenance of good health through the entire life course. However, in most western countries the annual increase in the prevalence and the severity of obesity and physical inactivity is substantial. Early detection of individuals with high risk for obesity is important, because reversing the obese state is very difficult. To prevent and treat obesity, it is necessary to characterize neural mechanisms supporting altered incentive motivation and food intake, and to build a comprehensive model of the interactions between neural, physiological, and psychological factors contributing to development and maintenance of obesity. This obviously calls for novel data analysis techniques allowing fusion analysis of neurobiological, physiological, and behavioural data, as well as screening the critical combination of biomarkers for obesity.

A total of sixty males (30 normal-weight, 30 with risk for developing obesity) are recruited into this prospective study. The subjects will undergo physical examination, physical fitness tests, physical activity measures, body tissue composition measurement, structural and functional magnetic resonance imaging of the brain and body (MRI & fMRI), and positron emission tomography (PET) with ligands [18F]-fluorodeoxyglucose ([18F]-FDG), [18-F]FMPEP, and [11C]carfentanil. Subjects' weight and physical condition will be followed up for 5 years.

In three interconnected work packages (WPs) we test three hypotheses derived from human and animal studies:

  1. Altered reward and cognitive control functions in the brain predisposes some individuals to overeating and obesity.
  2. Opioid system and reward circuit function provide feasible biomarkers for obesity risk.
  3. Mobile tracking and behavioural paradigms tapping reward learning and inhibitory control can be used for unobtrusive and inexpensive detection of risk factors for obesity.

These studies will improve our understanding of the neural and psychological mechanisms of obesity and addictive disorders. This knowledge will translate into crucial knowledge for developing novel risk factor screening procedures, and novel pharmacological and psychological treatments for obesity.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Non-Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Detecting Neuromolecular Risk Factors for Obesity
Actual Study Start Date : April 4, 2017
Estimated Primary Completion Date : December 1, 2022
Estimated Study Completion Date : December 1, 2022

Arm Intervention/treatment
Active Comparator: Low-risk group
Individuals in the low-risk group are not in a risk of developing obesity according to traditional risk criteria.
Diagnostic Test: fMRI imaging
Using blood oxygenation level dependent (BOLD) echo-planar imaging, fMRI will be used for characterising individual differences in the brain circuits.

Diagnostic Test: [11C]carfentanil PET scan
[11C]carfentanil is used to measure μ-opioid receptor (MOR) availability in brain.

Diagnostic Test: [18F]FMPEP-d2 PET scan
[18F]FMPEP-d2 is used to measure cannabinoid receptor type 1 (CB1) availability in brain and body.

Diagnostic Test: [18F]-FDG PET scan
Brain and body insuin stimulated glucose uptake is measured with radioligand [18F]-FDG.

Diagnostic Test: Physical activity measures and fitness tests
Physical activity will be measured over one week following the screening check-up, before the PET measurement days. For the measurement, subjects will wear Polar M600 GPS Sports Watch for the measurement period. The fitness tests will be performed at the Paavo Nurmi Centre.

Diagnostic Test: Laboratory measurements
Weight, height, blood pressure, medical history, and current medication are determined. Body fat percentage will be assessed using BodPod plethysmograph.

Diagnostic Test: Questionnaires
All the participants will complete a self-administered questionnaire at baseline, and at 12 months, for assessment of leisure-time physical activity (LTPA). The following questionnaires will be completed: Behavioural inhibition / activation, Dutch Eating Behaviour Questionnaire, Yale Food Addiction Scale, PCL-Revised, Food craving State / Trait (FCS-FCST) questionnaires, Autism Spectrum Quotient, State-Trait Anxiety Questionnaire and Pain Sensitivity Questionnaire.

Diagnostic Test: Hyperinsulinemic euglycemic clamp
Low-dose hyperinsulinemic euglycemic clamp technique will be used to promote glucose uptake and measure insulin sensitivity of the subjects. In the clamp study subjects are administered intravenous insulin at a steady rate of 0.25 mU/kg/min and normoglycemia is maintained using a variable rate infusion of 20 % glucose based on plasma glucose measurements, which are performed every 5-10 min from arterialized venous blood.

Active Comparator: High-risk group
Individuals in the high-risk group are in a risk of developing obesity according to traditional risk criteria.
Diagnostic Test: fMRI imaging
Using blood oxygenation level dependent (BOLD) echo-planar imaging, fMRI will be used for characterising individual differences in the brain circuits.

Diagnostic Test: [11C]carfentanil PET scan
[11C]carfentanil is used to measure μ-opioid receptor (MOR) availability in brain.

Diagnostic Test: [18F]FMPEP-d2 PET scan
[18F]FMPEP-d2 is used to measure cannabinoid receptor type 1 (CB1) availability in brain and body.

Diagnostic Test: [18F]-FDG PET scan
Brain and body insuin stimulated glucose uptake is measured with radioligand [18F]-FDG.

Diagnostic Test: Physical activity measures and fitness tests
Physical activity will be measured over one week following the screening check-up, before the PET measurement days. For the measurement, subjects will wear Polar M600 GPS Sports Watch for the measurement period. The fitness tests will be performed at the Paavo Nurmi Centre.

Diagnostic Test: Laboratory measurements
Weight, height, blood pressure, medical history, and current medication are determined. Body fat percentage will be assessed using BodPod plethysmograph.

Diagnostic Test: Questionnaires
All the participants will complete a self-administered questionnaire at baseline, and at 12 months, for assessment of leisure-time physical activity (LTPA). The following questionnaires will be completed: Behavioural inhibition / activation, Dutch Eating Behaviour Questionnaire, Yale Food Addiction Scale, PCL-Revised, Food craving State / Trait (FCS-FCST) questionnaires, Autism Spectrum Quotient, State-Trait Anxiety Questionnaire and Pain Sensitivity Questionnaire.

Diagnostic Test: Hyperinsulinemic euglycemic clamp
Low-dose hyperinsulinemic euglycemic clamp technique will be used to promote glucose uptake and measure insulin sensitivity of the subjects. In the clamp study subjects are administered intravenous insulin at a steady rate of 0.25 mU/kg/min and normoglycemia is maintained using a variable rate infusion of 20 % glucose based on plasma glucose measurements, which are performed every 5-10 min from arterialized venous blood.




Primary Outcome Measures :
  1. Neuromolecular risk score for weight gain [ Time Frame: Within five study years ]
    Acquired with combining the measured BMI change in five years to measured alterations in brain function (see below).


Secondary Outcome Measures :
  1. Localization of on-going neural activity during various cognitive and affective tasks [ Time Frame: Within one study day ]
    Acquired with fMRI imaging

  2. Brain and body glucose uptake [ Time Frame: Within one study day ]
    Acquired with PET imaging

  3. Brain and body CB1 availability [ Time Frame: Within one study day ]
    Acquired with PET imaging

  4. Brain MOR availability [ Time Frame: Within one study day ]
    Acquired with PET imaging

  5. Genes regulating MOR (OPRM1) and D2R (DRD2) expression [ Time Frame: Within one study week ]
    Acquired with whole blood sample and DNA/RNA analysis

  6. Genetic risk score from all known obesity-risk genes [ Time Frame: Within one study week ]
    Acquired with whole blood sample and DNA/RNA analysis

  7. Behavioural patterns involving dysfunctional reward learning and inhibitory control [ Time Frame: Within one study year ]
    Acquired with following questionnaires: assessment of leisure-time physical activity (LTPA), Behavioural inhibition / activation, Dutch Eating Behaviour Questionnaire, Yale Food Addiction Scale, PCL-Revised, Food craving State / Trait (FCS-FCST) questionnaires, Autism Spectrum Quotient, State-Trait Anxiety Questionnaire, Pain Sensitivity Questionnaire, DASS-21, PSS-10

  8. Physical activity level [ Time Frame: Within one study week ]
    Acquired with Polar M600 GPS Sports Watch that study subjects wear for the measurement period

  9. Maximal physical performance [ Time Frame: Within one study day ]
    The subjects will perform a maximal aerobic exercise test on a bicycle ergometer starting at the intensity of 50 W and followed by an increase of 30 W every 2 min until volitional exhaustion. Peak workload will be calculated as an average workload during the last 2 min of the test (weighted average will be used if the final stage is stopped prior the completion) and used as a measure of maximal performance of the subjects

  10. Physical strength [ Time Frame: Within one study day ]
    Total physical strenght score is calculated from 1) countermovement jump test with a contact mat (flight time measured - jump height calculated), hand grip strength (measured in Newtons), sit-ups (number of repetitions in 30 s), and back extension (reps in 30 s)

  11. BMI change in five years [ Time Frame: Within five study years ]
    Acquired with BMI of the study subjects measured in initial health check-up and once in every study year

  12. Body adiposity [ Time Frame: Within one study day ]
    Acquired with BodPod device (Frisard, Greenway, & DeLany, 2005)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   20 Years to 35 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

Inclusion criteria for low-risk group:

  • Male sex
  • Age 20-35 years
  • BMI 20-24 kg/m2
  • Physical exercise > 4 hrs per week
  • No maternal / paternal obesity OR maternal / paternal type 2 diabetes mellitus (T2DM)

Inclusion criteria for high-risk group:

  • Male sex
  • Age 20-35 years
  • BMI 25 - 30 kg/m2
  • Maternal / paternal obesity OR maternal / paternal T2DM
  • Physical exercise < 4 hrs per week

Exclusion Criteria:

  • Any chronic disease or medication that could affect glucose metabolism or neurotransmission
  • History of anorexia nervosa, bulimia or other eating disorder (excl. common obesity)
  • Smoking of tobacco, taking of snuffs, or use of narcotics
  • Abusive use of alcohol
  • Any other condition that in the opinion of the investigator could create a hazard to the subject safety, endanger the study procedures or interfere with the interpretation of study results

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03106688


Contacts
Layout table for location contacts
Contact: Pirjo Nuutila, M.D., Ph.D. +358 401626834 pirnuu@utu.fi

Locations
Layout table for location information
Finland
Turku PET Centre (Turku University Hospital) Recruiting
Turku, Finland, 20521
Contact: Pirjo Nuutila, M.D., Ph.D.       pirnuu@utu.fi   
Sponsors and Collaborators
Turku University Hospital
Investigators
Layout table for investigator information
Principal Investigator: Pirjo Nuutila, M.D., Ph.D. Turku PET Centre (Turku University Hospital)

Publications:
Layout table for additonal information
Responsible Party: Pirjo Nuutila, Professor, Turku University Hospital
ClinicalTrials.gov Identifier: NCT03106688     History of Changes
Other Study ID Numbers: PROSPECT
First Posted: April 10, 2017    Key Record Dates
Last Update Posted: May 1, 2017
Last Verified: April 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Pirjo Nuutila, Turku University Hospital:
PET imaging
Cannabinoid receptor
Opioid receptor
Addiction
fMRI imaging
Additional relevant MeSH terms:
Layout table for MeSH terms
Obesity
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms
Carfentanil
Analgesics, Opioid
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics
Sensory System Agents
Peripheral Nervous System Agents