The objectives of the study are 1) whether ResvidaTM is capable of increasing mitochondrial content and function in healthy obese subject, 2) whether the ResvidaTM induced increase in mitochondrial content and function is accompanied by a better fat…
ID
Source
Brief title
Condition
- Lipid metabolism disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary outcome parameter is the difference in mitochondrial number,
intrinsic function and fat oxidative capacity after a 4 week treatment with
ResvidaTM compared to the placebo trial.
Secondary outcome
Secondary endpoints are the differences in skeletal muscle and liver lipid
content, and lipolysis in skeletal muscle and adipose tissue after 4 weeks
ResvidaTM or placebo supplementation.
Background summary
There is now a general consensus that the combination of excessive energy
intake and a low capacity to oxidize fat will lead to muscular fat accumulation
and insulin resistance. It is known for many years that physical activity is
the most powerful treatment to combat obesity and insulin resistance, but it is
also known that it is difficult to get people to exercise. A major breakthrough
in this field has come from the nutrition field, with the finding that
resveratrol, a natural polyphenolic compound, could serve as an *exercise
mimetic* by protecting mice from many detrimental effects of diet-induced
obesity. Therefore we would like to investigate if resveratrol has the same
effects in obese humans as it does in mice on a diet-induced-obesity diet.
This information can then be used to develop new treatment for obesity.
Therefore, we would like to investigate whether ResvidaTM can increase
mitochondrial number together with an increased intrinsic activity and whether
this will lead to a better control of fatty acid handling in muscle.
Study objective
The objectives of the study are 1) whether ResvidaTM is capable of increasing
mitochondrial content and function in healthy obese subject, 2) whether the
ResvidaTM induced increase in mitochondrial content and function is accompanied
by a better fat oxidation, and 3) whether ResvidaTM increased lipolysis in
skeletal muscle and adipose tissue, thereby contributing to an improved fatty
acid handling
Study design
18 Healthy obese (BMI 30-35 kg/m2) male subjects, aged between 45-65 years old,
who are not engaged in regular programmed exercise are included in a
randomized, double blind cross-over design. Each subject will participate in
two interventions, in random order, en separated by a wash-out period of at
least 4 weeks. Each intervention period includes a 4 week (30 days)
supplementation with ResvidaTM or placebo. Before the start of the study,
subjects will be screened to access eligibility, which will a include a medical
questionnaire, a measurement of body weight and body composition (DEXA scan) to
determine fat content and drawing of a fasted blood sample. On day 0 subjects
will come to the university. A fasted blood sample will be drawn and body
weight will be checked. Hereafter, subjects will be offered a breakfast. After
consumption of the breakfast subjects will be asked to perform a maximal
aerobic capacity test. Before the test begins, heart rate and blood pressure
will be checked. During the test an ECG will be performed by an experienced and
trained person. Thereafter subjects can go home and they will receive enough
capsules for the first week of the intervention.Additional bloodsamples will be
taken weekly as well as a body weight measurement (day 7, 14, 21). During
these weekly visits, subjects will receive enough capsules for the next week.
On day 25 in vivo mitochondrial function and liver fat content will be measured
with MR spectroscopy. On day 28, in the evening, subjects will stay in the
respiration chamber during 36 hours and energy expenditure and fat oxidation
will be measured. During the stay in the respiration chamber blood will be
sampeled every 12 hours and during the last 24 hours urine will be collected
voor measurement of protein loss and for the measurement of metabolomics. On
day 30, in the morning, subjects will leave the respiration chamber and a blood
sample will be taken for measurement of total blood cell count, coagulants,
electrolytes, liver- and kidney function. In addition, an ECG will be performed
and blood pressure and heart rate will be measured. Thereafter, a muscle biopsy
will be taken and subsequently the microdialysis trial will be started in which
lipolysis in muscle en adipose tissue will be measured. At the end of the
microdialysis trial, a fat biopsy will be taken.
Intervention
Subjects will receive ResvidaTM or placebo in random order. ResvidaTM is a food
supplement and is regulated as a food component. ResvidaTM and placebo are
supplied by DSM Nutritional Products, ltd. For the product ResvidaTM the
maximal approved daily dosage in humans is 150 mg/ day. For higher doses the
safety concerns are not yet investigated. Therefore, we have chosen to
supplement the subjects with a dose of 150 mg/ day, spread out over doses of 75
mg twice a day with lunch and diner.
Study burden and risks
Before the start of the study, subjects will be screened to access eligibility
which will include a medical questionnaire, measurement of body weight and body
composition (DEXA scan). A fasted bloodsample will also be drawn (duration: 1
hour). Thereafter, they will be randomized and undergo two intervention periods
of 4 weeks separated by a wash-out period of at least 4 weeks. The subjects
will come to the University 6 times (day 0, 7, 14, 21, 25, 28). During these
visits at the University, a bloodsample will be taken weekly as well as a
weekly measurement of body weight (day 0, 7, 14, 21), a maximal aerobic
capacity test will be performed (day 0) and in vivo mitochondrial function and
liver fat content will be measured with MRS (day 25). In addition, subjects
will stay in the respiration chamber for 36 hours (2 nights and 1 day) (day
28-30) after which a muscle biopsy will be taken and the microdialysis trial
will be started. At the end of the microdialysis trial, a fat biopsy will be
taken.
P.O Box 616
6200 MD Maastricht
Nederland
P.O Box 616
6200 MD Maastricht
Nederland
Listed location countries
Age
Inclusion criteria
* Male sex
* Age 45-65 years
* Body fat percentage > 25, BMI 30-35 kg/m2
* Sedentary
* Stable dietary habits
* Willingness to abstain from ingestion of resveratrol-containing foods
* Healthy
Exclusion criteria
* Female sex
* Unstable body weight (weight gain or loss > 3 kg in the last three months)
* Total body fat (%) < 25%
* Fasting plasma glucose > 6.1 mmol/l
HB < 7.8 mmol/l
* Engagement in programmed exercise > 2 hours total per week
* Impaired kidney and/ or hepatic function
* First- or second-degree family member with type 2 diabetes mellitus
* Any medical condition requiring treatment and/or medication use
* Intake of dietary supplements except vitamins and minerals
* Unwilling to restrict high-resveratrol-containing foods
* Current alcohol consumption > 20 grams/day
* Participation in another biomedical study within 1 month before the first screening visit
* A contraindication to MRI scanning. These contra-indications include patients with the following devices:
o Central nervous system aneurysm clips
o Implanted neural stimulator
o Implanted cardiac pacemaker of defibrillator
o Cochlear implant
o Insulin pump
o metal containing corpora aliena in the eye or brains
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL28654.068.09 |
| Other | www.clinicaltrials.gov |