Baseline Physiology Studies in Carriers of Gene Variant X Conferring Major Risk of CVD-prone Metabolic Disorders

Sponsor

University of Aarhus (Other)

Overall Status

Completed

CT.gov ID

NCT01571609

Collaborator

Lundbeck Foundation (Other), Aarhus University Hospital (Other), Vejle Hospital (Other), Sydvestjysk Hospital (Other), Steno Diabetes Center Copenhagen (Other), University of Copenhagen (Other)

Enrollment

Location

Arms

Duration (Months)

1.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of the present study is to conduct a thorough and relevant physiology study of carriers and non-carriers of the gene variant X in order to determine the effect of the genetic variant on various metabolic parameters.

Condition or Disease	Intervention/Treatment	Phase
Hyperlipidemia Diabetes Mellitus Metabolic Syndrome Arterial Hypertension Obesity	Other: first phase insulin secretion (FPIR), Hyperinsulinemic euglycemic clamp (HEC), glucose tracer, and palmitate tracer	N/A

Study Design

Study Type:

Interventional

Actual Enrollment :

40 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

Baseline Physiology Studies in Carriers of Gene Variant X Conferring Major Risk of CVD-prone Metabolic Disorders

Study Start Date :

Aug 1, 2012

Actual Primary Completion Date :

Jul 1, 2013

Actual Study Completion Date :

Nov 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Carriers	Other: first phase insulin secretion (FPIR), Hyperinsulinemic euglycemic clamp (HEC), glucose tracer, and palmitate tracer FPIR: intravenous infusion of 20 % glucose 0.3 mg/kg in 2 minutes followed by blood sampling at times 0, 2, 4, 6, 8, and 10. Duration 10 minutes. HEC: intravenous infusion of actrapid 1mU/kg/minute, simultaneous infusion of 20 % glucose at variable rate to reach plasma blood glucose level of 5 mmol/L. Duration 120 minutes Glucose tracer: bolus of 3H3glucose (12µCi) followed by infusion of 3H3glucose (0,12 µCi/min). Duration 120 minutes. Palmitate tracer:[9,10-3H]-palmitate 0,3 µCi/min. Duration 60 minutes.
Experimental: Non-carriers	Other: first phase insulin secretion (FPIR), Hyperinsulinemic euglycemic clamp (HEC), glucose tracer, and palmitate tracer FPIR: intravenous infusion of 20 % glucose 0.3 mg/kg in 2 minutes followed by blood sampling at times 0, 2, 4, 6, 8, and 10. Duration 10 minutes. HEC: intravenous infusion of actrapid 1mU/kg/minute, simultaneous infusion of 20 % glucose at variable rate to reach plasma blood glucose level of 5 mmol/L. Duration 120 minutes Glucose tracer: bolus of 3H3glucose (12µCi) followed by infusion of 3H3glucose (0,12 µCi/min). Duration 120 minutes. Palmitate tracer:[9,10-3H]-palmitate 0,3 µCi/min. Duration 60 minutes.

Arm

Intervention/Treatment

Experimental: Carriers

Other: first phase insulin secretion (FPIR), Hyperinsulinemic euglycemic clamp (HEC), glucose tracer, and palmitate tracer

FPIR: intravenous infusion of 20 % glucose 0.3 mg/kg in 2 minutes followed by blood sampling at times 0, 2, 4, 6, 8, and 10. Duration 10 minutes. HEC: intravenous infusion of actrapid 1mU/kg/minute, simultaneous infusion of 20 % glucose at variable rate to reach plasma blood glucose level of 5 mmol/L. Duration 120 minutes Glucose tracer: bolus of 3H3glucose (12µCi) followed by infusion of 3H3glucose (0,12 µCi/min). Duration 120 minutes. Palmitate tracer:[9,10-3H]-palmitate 0,3 µCi/min. Duration 60 minutes.

Experimental: Non-carriers

Other: first phase insulin secretion (FPIR), Hyperinsulinemic euglycemic clamp (HEC), glucose tracer, and palmitate tracer

Outcome Measures

Primary Outcome Measures

insulin secretion [10 minutes]
Estimation of first phase insulin secretion

Secondary Outcome Measures

Insulin resistance [240 minutes]
Estimation of insulin resistance using hyperinsulinemic euglycemic clamp and glucose and lipid tracers
body composition [60 minutes]
Evaluation of body composition using Dxa scan and MRI scan
atherosclerosis [30 minutes]
Evaluation of presence and severity of atherosclerosis using ultrasound scan of the common carotide artery
biochemical blood profiling [at baseline]
Various tests run on blood samples
Insulin resistance [60 minutes]
Biopsi from muscle and adipose tissue performed at baseline and during clamp study.
Blood pressure [24 hours]
Measurement of blood pressure every 20. minutes/24 hours
Indirect calorimetry [60 minutes]
Estimation of resting energy expenditure and respiratory quotient

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Male
18-70 years of age
Member of Biobank Vejle
BMI<30

Exclusion Criteria:

Diabetes mellitus
Severe illness

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Medicinsk forskningslaboratorium, Aarhus Universitet	Aarhus		Denmark	8000

Sponsors and Collaborators

University of Aarhus
Lundbeck Foundation
Aarhus University Hospital
Vejle Hospital
Sydvestjysk Hospital
Steno Diabetes Center Copenhagen
University of Copenhagen

Investigators

Principal Investigator: Niels Møller, Professor, University of Aarhus
Principal Investigator: Oluf B Pedersen, Professor, Steno Diabetes Center Copenhagen
Principal Investigator: Torben Hansen, Professor, Steno Diabetes Center Copenhagen
Principal Investigator: Jørgen Rungby, Professor, University of Aarhus