Body Weight and Vascular Function

Obesity Clinical Trial

Official title:

Vascular Function Markers: Differences Between Lean and Abdominally Overweight / Obese Men and Effects of Weight Loss

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01675401
• Other study ID #: MEC 12-3-040
• Status: Completed
• Phase: N/A
• First received: August 21, 2012
• Last updated: October 31, 2016
• Start date: September 2012
• Est. completion date: May 2014

Study information

• Verified date: October 2016
• Source: Maastricht University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial Summary

An increased body mass impairs vascular function (VF), an important characteristic of subjects suffering from type 2 diabetes and a risk marker for cardiovascular diseases. However, a wide variety of in vivo VF markers exists each measuring different aspects of VF. Each of these markers addresses a different aspect of the vasculature. Studies comparing under standardized conditions the differences and relationships of the many different VF measurements in lean and abdominally overweight / obese subjects are missing. Also, there is a great need to know which of these markers are sensitive to dietary challenges.

Therefore, it is imperative to conduct an extensive study on dietary effects and interrelationships of a broad spectrum of VF measurements and plasma biomarkers in lean and overweight / obese subjects. Focus will be on FMD, a well accepted biomarker for cardiovascular disease. The investigators propose to examine, in a two-way parallel-randomized human intervention study, the effects of weight-loss in abdominally overweight / obese men on VF markers and plasma biomarkers related to low-grade inflammation and vascular activity during the fasting and both the postprandial and hyperinsulinemic state. Furthermore, differences - and relations between - VF measurements and plasma biomarkers will be compared cross-sectionally between lean and abdominally overweight / obese male subjects.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 75
• Est. completion date: May 2014
• Est. primary completion date: May 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Aged between 18 and 65 years

• Waist circumference below 94 cm (lean subjects) or between 102 - 110 cm (abdominally overweight / obese subjects)

• Caucasian

• Plasma glucose < 7.0 mmol/L

• Serum total cholesterol < 8.0 mmol/L

• Serum triacylglycerol < 4.5 mmol/L

• Plasma HbA1c < 6.5%

• No current smoker

• No diabetic patients

• No familial hypercholesterolemia

• No abuse of drugs

• Less than 14 alcoholic consumptions per week

• Stable body weight (weight gain or loss < 3 kg in the past three months)

• No use of medication known to affect blood pressure, serum lipid or glucose metabolism

• No severe medical conditions that might interfere with the study, such as epilepsy, asthma, chronic obstructive pulmonary disease, inflammatory bowel diseases, auto inflammatory diseases and rheumatoid arthritis

• No active cardiovascular disease like congestive heart failure or cardiovascular event, such as an acute myocardial infarction or cerebrovascular accident

• No contra-indications for MRI imaging

• Willingness to give up being a blood donor (or having donated blood) from 8 weeks before the start of the study, during the study and for 4 weeks after completion of the study

• No difficult venipuncture as evidenced during the screening visit

Exclusion Criteria:

• Women

• Non-caucasian

• Plasma glucose = 7.0 mmol/L

• Serum total cholesterol = 8.0 mmol/L

• Serum triacylglycerol = 4.5 mmol/L

• Plasma HbA1c = 6.5%

• Current smoker, or smoking cessation < 12 months

• Diabetic patients

• Familial hypercholesterolemia

• Abuse of drugs

• More than 14 alcoholic consumptions per week

• Unstable body weight (weight gain or loss > 3 kg in the past three months)

• Use of use of medication known to affect blood pressure, serum lipid or glucose metabolism

• Severe medical conditions that might interfere with the study, such as epilepsy, asthma, chronic obstructive pulmonary disease, inflammatory bowel diseases, auto inflammatory diseases and rheumatoid arthritis

• Active cardiovascular disease like congestive heart failure or cardiovascular event, such as an acute myocardial infarction or cerebrovascular accident

• Contra-indications for MRI imaging

• Use of an investigational product within the previous 1-month

• Not willing to give up being a blood donor (or having donated blood) from 8 weeks before the start of the study, during the study or for 4 weeks after completion of the study

• Not or difficult to venipuncture as evidenced during the screening visit

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Body Weight
• Metabolic Syndrome
• Metabolic Syndrome X
• Obesity

Intervention

Other:
• Weight-loss treatment
A very-low energy diet (Modifast Intensive) for 4-5 weeks providing 2.1 MJ/day in order to reduce body weight. After 4-5 weeks a mixed solid energy-restricted diet up to 4.2 MJ/day with a recommended composition for the following 1-2 weeks. Then, a diet matching their energy requirements to maintain newly achieved body weights (weight-stable conditions) for at least 2 weeks.
• No-weight loss treatment
Maintenance of habitual diet and physical activity for 8 weeks to maintain body weights.

Locations

Country	Name	City	State
Netherlands	Maastricht University Medical Center	Maastricht

Sponsors (2)

Lead Sponsor	Collaborator
Maastricht University Medical Center	Top Institute Food and Nutrition

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Body fat components and fat content of intra-abdominal organs: differences between lean and abdominally overweight / obese men and effects of weight loss	Dixon MRI measurements in order to quantify abdominal fat compartments (i.e. subcutaneous and visceral fat) and fat content of abdominal organs (i.e. liver).	Difference after weight-loss due to restriction of energy intake for 8 weeks	No
Other	Blood pressure: difference between lean and abdominally overweight / obese men and effects of weight loss	24-hr ambulatory blood pressure	Difference after weight-loss due to restriction of energy intake for 8 weeks	No
Primary	Vascular activity: differences between lean and abdominally overweight / obese men and effects of weight loss	Flow-mediated dilation (FMD) of the brachial artery.	Difference after weight-loss due to restriction of energy intake for 8 weeks and change from baseline at 2 hours after meal consumption	No
Secondary	Vascular function markers related to the macrovasculature: differences between lean and abdominally overweight / obese men and effects of weight loss	Carotid-wall intima-media thickness (IMT), carotid compliance and distensibility, pulse wave velocity and analysis (PWV and PWA) and peripheral artery tonometry (PAT).	Difference after weight-loss due to restriction of energy intake for 8 weeks and change from baseline during the postprandial (at 2 hours after meal consumption) / hyperinsulinemic state (at 2 hours after initiation of the clamp)	No
Secondary	Vascular function markers related to the microvasculature: differences between lean and abdominally overweight / obese men and effects of weight loss	Capillary video microscopy of the finger skin, skin microvascular vasomotion, glycocalyx thickness, retina photography, skin auto fluorescence and contrast enhanced ultrasound (CEUS) in skeletal muscle.	Difference after weight-loss due to restriction of energy intake for 8 weeks and change from baseline during the postprandial (at 1 and 3 hours after meal consumption) / hyperinsulinemic state (at 2 hours after initiation of the clamp)	No
Secondary	Metabolic risk markers related to the metabolic syndrome: differences between lean and abdominally overweight / obese men and effects of weight loss	Biomarkers for low-grade inflammation and endothelial activation.	Difference after weight-loss due to restriction of energy intake for 8 weeks and change from baseline during the postprandial (during 4 hours after meal consumption) / hyperinsulinemic state (during 3 hours after initiation of the clamp)	No