Clinical trial NCT01675401: Body Weight and Vascular Function
Official title: Vascular Function Markers: Differences Between Lean and Abdominally Overweight / Obese Men and Effects of Weight Loss
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Metabolic Syndrome
Obesity
Keywords: Body Weight
Obesity
Weight Loss
Vascular Function Markers
Lead sponsor: Maastricht University Medical Center
Sponsor class: OTHER
Collaborators: name: Top Institute Food and Nutrition
First posted: 2012-08-30
Enrollment: 75
Sex: MALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Vascular activity: differences between lean and abdominally overweight / obese men and effects of weight loss
timeFrame: Difference after weight-loss due to restriction of energy intake for 8 weeks and change from baseline at 2 hours after meal consumption
Secondary outcomes:
measure: Vascular function markers related to the macrovasculature: differences between lean and abdominally overweight / obese men and effects of weight loss
timeFrame: 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)
measure: Vascular function markers related to the microvasculature: differences between lean and abdominally overweight / obese men and effects of weight loss
timeFrame: 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)
measure: Metabolic risk markers related to the metabolic syndrome: differences between lean and abdominally overweight / obese men and effects of weight loss
timeFrame: 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)
Other outcomes:
measure: Body fat components and fat content of intra-abdominal organs: differences between lean and abdominally overweight / obese men and effects of weight loss
timeFrame: Difference after weight-loss due to restriction of energy intake for 8 weeks
measure: Blood pressure: difference between lean and abdominally overweight / obese men and effects of weight loss
timeFrame: Difference after weight-loss due to restriction of energy intake for 8 weeks
Locations:
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Center
Study officials:
affiliation: Maastricht University Medical Center
name: Ronald P Mensink, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Maastricht University Medical Center
name: Casper G Schalkwijk, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Van den Eynde MDG, Kusters YHAM, Houben AJHM, Scheijen JLJM, van Duynhoven J, Fazelzadeh P, Joris PJ, Plat J, Mensink RP, Hanssen NMJ, Stehouwer CDA, Schalkwijk CG. Diet-induced weight loss reduces postprandial dicarbonyl stress in abdominally obese men: Secondary analysis of a randomized controlled trial. Clin Nutr. 2021 May;40(5):2654-2662. doi: 10.1016/j.clnu.2021.03.042. Epub 2021 Apr 15.
citation: Joris PJ, Plat J, Kusters YHAM, Houben AJHM, Stehouwer CDA, Schalkwijk CG, Mensink RP. Effects of diet-induced weight loss on postprandial vascular function after consumption of a mixed meal: Results of a randomized controlled trial with abdominally obese men. Clin Nutr. 2020 Oct;39(10):2998-3004. doi: 10.1016/j.clnu.2020.01.006. Epub 2020 Jan 13.
citation: Fazelzadeh P, Hoefsloot HCJ, Hankemeier T, Most J, Kersten S, Blaak EE, Boekschoten M, van Duynhoven J. Global testing of shifts in metabolic phenotype. Metabolomics. 2018 Oct 4;14(10):139. doi: 10.1007/s11306-018-1435-8.
citation: Telgenkamp I, Kusters YHAM, Schalkwijk CG, Houben AJHM, Kooi ME, Lindeboom L, Bons JAP, Schaper NC, Joris PJ, Plat J, Mensink RP, Stehouwer CDA, Brouwers MCGJ. Contribution of Liver Fat to Weight Loss-Induced Changes in Serum Hepatokines: A Randomized Controlled Trial. J Clin Endocrinol Metab. 2019 Jul 1;104(7):2719-2727. doi: 10.1210/jc.2018-02378.
citation: Schutten MTJ, Kusters YHAM, Houben AJHM, Scheijen JLJM, van de Waarenburg MPH, Schalkwijk CG, Joris PJ, Plat J, Mensink RP, de Leeuw PW, Stehouwer CDA. Aldosterone Is Not Associated With Metabolic and Microvascular Insulin Sensitivity in Abdominally Obese Men. J Clin Endocrinol Metab. 2018 Feb 1;103(2):759-767. doi: 10.1210/jc.2017-01541.
citation: Kusters YH, Schalkwijk CG, Houben AJ, Kooi ME, Lindeboom L, Op 't Roodt J, Joris PJ, Plat J, Mensink RP, Barrett EJ, Stehouwer CD. Independent tissue contributors to obesity-associated insulin resistance. JCI Insight. 2017 Jul 6;2(13):e89695. doi: 10.1172/jci.insight.89695. eCollection 2017 Jul 6.
citation: Joris PJ, Plat J, Kusters YH, Houben AJ, Stehouwer CD, Schalkwijk CG, Mensink RP. Diet-induced weight loss improves not only cardiometabolic risk markers but also markers of vascular function: a randomized controlled trial in abdominally obese men. Am J Clin Nutr. 2017 Jan;105(1):23-31. doi: 10.3945/ajcn.116.143552. Epub 2016 Nov 23.