Obesity and Brain: Genes and Environment

Obesity Clinical Trial

Official title:

The Role of Central Reward and Satiety Centers in the Etiology of Obesity: Genetic and Environmental Influences

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02025595
• Other study ID #: DC2013ObesiBrain001
• Secondary ID: NL 44735.029.139
• Status: Completed
• Phase: N/A
• First received: December 13, 2013
• Last updated: May 9, 2017
• Start date: December 2013
• Est. completion date: September 2016

Study information

• Verified date: May 2017
• Source: VU University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The aim of this study is to investigate the effects of genetic and environmental risk factors on central nervous system (CNS) reward and satiety circuits in the etiology of obesity. The investigators will also investigate to what extent the alterations in CNS reward and satiety circuits are a cause or a consequence of the development of obesity.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 92
• Est. completion date: September 2016
• Est. primary completion date: September 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Age 18-75 years

• Male or female

• Stable bodyweight (<5% reported weight change during previous 3 months)

• Women: regular menstruation cycle (to exclude possible menstruation cycle effects)

• Normal fasting blood glucose

Exclusion Criteria:

• Left handedness

• Known diabetes or abnormal fasting blood glucose

• Serious heart, pulmonary, hepatic or renal disease, malignant or hematological disease

• Metabolic disorders (uncontrolled adrenal/thyroid disease)

• Women: irregular menstruation cycle

• Neurological or psychiatric illness

• Pregnancy or breast feeding

• Alcohol abuse

• Nicotine abuse

• Claustrophobia or metal implants

• Visual disability

• Participation in another study

• Inability to understand the protocol or to give informed consent

• Current/chronic use of following medication: antihyperglycemic agents, glucocorticoids, centrally acting drugs, cytostatics, immune suppressants, potentially addictive medications.

Related Conditions & MeSH terms

• Obesity

Locations

Country	Name	City	State
Netherlands	VU University Medical Center	Amsterdam

Sponsors (1)

Lead Sponsor	Collaborator
VU University Medical Center

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	The difference within obesity-discordant monozygotic (MZ) twin pairs regarding gut microbiota composition	Gut microbiota composition (ratio between various gut microbiota species) will be assessed by identifying microbial phylotypes in a feces sample using 16S ribosomal RNA molecule-based approaches of diagnostic analysis. Function of gut microbiota will be investigated using metaproteomics analysis techniques that include mass-spectroscopy methodologies.; Please note: this outcome measure is conditional to available budget.	Baseline (one measurement)
Other	The difference within obesity-discordant monozygotic (MZ) twin pairs regarding epigenetic changes	Epigenetic changes will be assessed by measuring global DNA methylation (%) and locus specific DNA methylation (%) in regions of selected loci using a mass spectrometry-based method. Loci will be selected on the basis of their previously shown features of epigenetic regulation and their involvement in cardiovascular and metabolic disease.; Please note: this outcome measure is conditional to available budget.	Baseline (one measurement)
Other	The difference between individuals at high versus those at low genetic obesity risk regarding gut microbiota composition	Gut microbiota composition (ratio between various gut microbiota species) will be assessed by identifying microbial phylotypes in a feces sample using 16S ribosomal RNA molecule-based approaches of diagnostic analysis. Function of gut microbiota will be investigated using metaproteomics analysis techniques that include mass-spectroscopy methodologies.; Please note: this outcome measure is conditional to available budget.	Baseline (one measurement)
Other	The difference between individuals at high versus those at low genetic obesity risk regarding epigenetic changes	Epigenetic changes will be assessed by measuring global DNA methylation (%) and locus specific DNA methylation (%) in regions of selected loci using a mass spectrometry-based method. Loci will be selected on the basis of their previously shown features of epigenetic regulation and their involvement in cardiovascular and metabolic disease.; Please note: this outcome measure is conditional to available budget.	Baseline (one measurement)
Primary	The difference in neuronal activity in CNS reward and satiety circuits as represented by BOLD functional magnetic resonance imaging (fMRI) signal change from baseline (%) in response to food-related stimuli within obesity discordant MZ twin pairs.		Baseline (one measurement)
Primary	The difference in neuronal activity in CNS reward and satiety circuits as represented by BOLD fMRI signal change from baseline (%) in response to food-related stimuli between individuals at high verses low genetic obesity risk.		Baseline (one measurement)
Primary	The difference in neuronal activity in CNS reward and satiety circuits as represented by BOLD fMRI signal change from baseline (%) in response to food-related stimuli between lean and obese subjects with either high or low genetic obesity risk.		Baseline (one measurement)
Secondary	The difference within obesity-discordant monozygotic (MZ) twin pairs regarding dietary intake	Dietary intake will be measured as quantitative (kcal/day) and qualitative (energy density (kcal/kg) and macronutrient composition (%)) dietary intake using A) a choice lunch buffet on the visit day and B) the 24 hours recall method on two week days and one weekend day at home.	Baseline (one measurement)
Secondary	The difference within obesity-discordant monozygotic (MZ) twin pairs regarding physical activity level	Physical activity level will be measured as metabolic equivalent of task (METs)-hours per week using seven-day ActiGraph triaxial accelerometry at home.	Baseline (one measurement)
Secondary	The difference within obesity-discordant monozygotic (MZ) twin pairs regarding basal metabolic rate	Basal metabolic rate will be measured in kcal/day using oxygen consumption and carbon dioxide production measured by indirect calorimetry using a ventilated hood system.	Baseline (one measurement)
Secondary	The difference within obesity-discordant monozygotic (MZ) twin pairs regarding fasting circulating biomarker levels	Fasting circulating biomarker levels (glucose (mmol/l), HbA1c (mmol/mol), insulin (pmol/l), C-peptide (nmol/l), glucagon (pmol/l), triglycerides (mmol/l), HDL-cholesterol (mmol/l) and LDL-cholesterol (mmol/l)) will be measured in a fasting blood sample.	Baseline (one measurement)
Secondary	The difference within obesity-discordant monozygotic (MZ) twin pairs regarding autonomic nervous system balance	Autonomic nervous system balance will be assessment based on measurements of A) heart rate variability (HRV; calculated as root mean square of successive R-R interval differences (RMSSD) in ms2); B) respiratory rate (RR; breaths/min) and C) respiratory sinus arrhythmia (RSA; ms) in resting conditions and in response to a mental arithmetic task using an electro- and impedance cardiogram.	Baseline (one measurement)
Secondary	The difference between individuals at high versus those at low genetic obesity risk regarding dietary intake	Dietary intake will be measured as quantitative (kcal/day) and qualitative (energy density (kcal/kg) and macronutrient composition (%)) dietary intake using A) a choice lunch buffet on the visit day and B) the 24 hours recall method on two week days and one weekend day at home.	Baseline (one measurement)
Secondary	The difference between individuals at high versus those at low genetic obesity risk regarding physical activity level	Physical activity level will be measured as metabolic equivalent of task (METs)-hours per week using seven-day ActiGraph triaxial accelerometry at home.	Baseline (one measurement)
Secondary	The difference between individuals at high versus those at low genetic obesity risk regarding basal metabolic rate	Basal metabolic rate will be measured in kcal/day using oxygen consumption and carbon dioxide production measured by indirect calorimetry using a ventilated hood system.	Baseline (one measurement)
Secondary	The difference between individuals at high versus those at low genetic obesity risk regarding fasting circulating biomarker levels	Fasting circulating biomarker levels (glucose (mmol/l), HbA1c (mmol/mol), insulin (pmol/l), C-peptide (nmol/l), glucagon (pmol/l), triglycerides (mmol/l), HDL-cholesterol (mmol/l) and LDL-cholesterol (mmol/l)) will be measured in a fasting blood sample.	Baseline (one measurement)
Secondary	The difference between individuals at high versus those at low genetic obesity risk regarding autonomic nervous system balance	Autonomic nervous system balance will be assessment based on measurements of A) heart rate variability (HRV; calculated as root mean square of successive R-R interval differences (RMSSD) in ms2); B) respiratory rate (RR; breaths/min) and C) respiratory sinus arrhythmia (RSA; ms) in resting conditions and in response to a mental arithmetic task using an electro- and impedance cardiogram.	Baseline (one measurement)