Neuromolecular Risk Factors for Obesity (PROSPECT)

NCT ID: NCT03106688

Last Updated: 2021-12-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-04-04

Study Completion Date

2022-12-01

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Obesity

Keywords

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PET imaging Cannabinoid receptor Opioid receptor Addiction fMRI imaging

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

FACTORIAL

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

Study Groups

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Low-risk group

Individuals in the low-risk group are not in a risk of developing obesity according to traditional risk criteria.

Group Type ACTIVE_COMPARATOR

fMRI imaging

Intervention Type DIAGNOSTIC_TEST

Using blood oxygenation level dependent (BOLD) echo-planar imaging, fMRI will be used for characterising individual differences in the brain circuits.

[11C]carfentanil PET scan

Intervention Type DIAGNOSTIC_TEST

\[11C\]carfentanil is used to measure μ-opioid receptor (MOR) availability in brain.

[18F]FMPEP-d2 PET scan

Intervention Type DIAGNOSTIC_TEST

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

[18F]-FDG PET scan

Intervention Type DIAGNOSTIC_TEST

Brain and body insuin stimulated glucose uptake is measured with radioligand \[18F\]-FDG.

Physical activity measures and fitness tests

Intervention Type DIAGNOSTIC_TEST

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.

Laboratory measurements

Intervention Type DIAGNOSTIC_TEST

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

Questionnaires

Intervention Type DIAGNOSTIC_TEST

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.

Hyperinsulinemic euglycemic clamp

Intervention Type DIAGNOSTIC_TEST

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.

High-risk group

Individuals in the high-risk group are in a risk of developing obesity according to traditional risk criteria.

Group Type ACTIVE_COMPARATOR

fMRI imaging

Intervention Type DIAGNOSTIC_TEST

Using blood oxygenation level dependent (BOLD) echo-planar imaging, fMRI will be used for characterising individual differences in the brain circuits.

[11C]carfentanil PET scan

Intervention Type DIAGNOSTIC_TEST

\[11C\]carfentanil is used to measure μ-opioid receptor (MOR) availability in brain.

[18F]FMPEP-d2 PET scan

Intervention Type DIAGNOSTIC_TEST

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

[18F]-FDG PET scan

Intervention Type DIAGNOSTIC_TEST

Brain and body insuin stimulated glucose uptake is measured with radioligand \[18F\]-FDG.

Physical activity measures and fitness tests

Intervention Type DIAGNOSTIC_TEST

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.

Laboratory measurements

Intervention Type DIAGNOSTIC_TEST

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

Questionnaires

Intervention Type DIAGNOSTIC_TEST

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.

Hyperinsulinemic euglycemic clamp

Intervention Type DIAGNOSTIC_TEST

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.

Interventions

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fMRI imaging

Using blood oxygenation level dependent (BOLD) echo-planar imaging, fMRI will be used for characterising individual differences in the brain circuits.

Intervention Type DIAGNOSTIC_TEST

[11C]carfentanil PET scan

\[11C\]carfentanil is used to measure μ-opioid receptor (MOR) availability in brain.

Intervention Type DIAGNOSTIC_TEST

[18F]FMPEP-d2 PET scan

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

Intervention Type DIAGNOSTIC_TEST

[18F]-FDG PET scan

Brain and body insuin stimulated glucose uptake is measured with radioligand \[18F\]-FDG.

Intervention Type 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.

Intervention Type DIAGNOSTIC_TEST

Laboratory measurements

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

Intervention Type 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.

Intervention Type 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.

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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Inclusion Criteria

* 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)


* 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
Minimum Eligible Age

20 Years

Maximum Eligible Age

35 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

Yes

Sponsors

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Turku University Hospital

OTHER_GOV

Sponsor Role lead

Responsible Party

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Pirjo Nuutila

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Pirjo Nuutila, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Turku PET Centre (Turku University Hospital)

Locations

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Turku PET Centre (Turku University Hospital)

Turku, , Finland

Site Status

Countries

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Finland

References

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Frisard MI, Greenway FL, Delany JP. Comparison of methods to assess body composition changes during a period of weight loss. Obes Res. 2005 May;13(5):845-54. doi: 10.1038/oby.2005.97.

Reference Type BACKGROUND
PMID: 15919837 (View on PubMed)

Other Identifiers

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PROSPECT

Identifier Type: -

Identifier Source: org_study_id