The overall objective is to investigate the efficacy of resveratrol in modulating metabolism and CVD risk profile in patients with COPD. The primary objective is to investigate the effect of resveratrol on CRP as clinical marker of low grade…
ID
Source
Brief title
Condition
- Cardiac disorders, signs and symptoms NEC
- Muscle disorders
- Bronchial disorders (excl neoplasms)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary outcome of this study is:
High sensitivity systemic inflammation (CRP) as a clinical marker of systemic
inflammation via blood sampling.
Secondary outcome
Secondary outcomes of this study are:
Proposed mechanisms of action:
1. Quadriceps metabolism and mitochondrial function via vastus lateralis muscle
biopsy and muscle cross-sectional area;
2. Adipose tissue inflammation via abdominal subcutaneous adipose tissue biopsy
(macrophage infiltration, adipocytes size, inflammatory and metabolic gene
expression);
3. Systemic inflammatory (IL-6, TNF-α, leptin and adiponectin) and oxidative
stress markers, cellular redox status and glutathionylation of haemoglobin via
blood sampling;
4. Lipid profile (triglyceride, total cholesterol, HDL cholesterol, apoA1,
apoB100) via blood sampling;
5. Insulin sensitivity: Homeostatis Model Assessment of insulin resistance
(HOMA-IR) index (blood);
General markers of body composition and health status known to be affected by
CRP:
1. Body fat mass and distribution: Whole-body fat mass (DXA scan and
anthropometric measurements) and visceral fat (DXA scan);
2. Quadriceps function by leg dynamometry (Biodex);
3. Blood pressure and heart rate (hematometer);
4. Physical activity level
Background summary
In the general population cardiovascular disease (CVD) is the leading cause of
mortality and it is well established that obesity (body mass index >30 kg/m²)
is an important determinant. The risk is even further increased in COPD due to
smoking behaviour and accumulation of visceral fat combined with a decreased
skeletal muscle oxidative capacity. Enhanced systemic inflammation is
identified as important driver in recent epidemiological and translational
research. Aerobic exercise training (AET) is an established way to improve
metabolic health and decrease CVD risk in the overweight general population but
modulating potential is limited in COPD due to ventilatory limitations and
related disease symptoms. Interventions which mimic the effects of AET are
therefore considered as unmet medical need. Evidence is emerging that the
nutritional supplement resveratrol is an interesting candidate that requires
further investigation in COPD.
Study objective
The overall objective is to investigate the efficacy of resveratrol in
modulating metabolism and CVD risk profile in patients with COPD.
The primary objective is to investigate the effect of resveratrol on CRP as
clinical marker of low grade systemic inflammation.
The secondary objective is to investigate the effect of resveratrol on body
composition, inflammatory status and mechanistic markers in blood, adipose and
muscle tissue as well as a comprehensive assessment of metabolic and physical
performance profile known to be affected by low grade systemic inflammation and
by resveratrol.
Study design
The research aims will be addressed in a proof-of-concept randomized
placebo-controlled double blinded clinical trial comparing 2 groups of 26
subjects each.
Intervention
Subjects will be randomized to one of the research groups. The groups will
receive the following intervention:
- Group 1 will receive a dose of 150 mg of resveratrol for 4 weeks (2 capsules
of 220 mg/day)
- Group 2 will receive a placebo for 4 weeks (2 capsules of 220 mg/day)
Study burden and risks
We will perform reversibility measurements for lung function. This includes the
inhalation of a short acting bronchodilator. This is a standard procedure for
the diagnose COPD. The inhalation of the bronchodilator may sometimes be
associated with dizziness and palpitations. However, this will resolve shortly
after inhalation. Furthermore, subjects will be asked to wear an accelerometer
two times for one week. This is a small device which can be worn as a belt
around the waist and it will not hinder any daily activities. However, because
subjects are not used to wearing this small device they might experience this
as uncomfortable. Some measurements we are performing are invasive and not
without any risk. Venous blood will be drawn and muscle and fat biopsies will
be taken which can cause a local haematoma. Subjects using anti-coagulants are
excluded from this procedure for this reason. Infection or bleedings on the
other hand are very rare. The subjects will be instructed to refrain from heavy
physical labour and not to remove the pressure bandage from the leg where the
biopsy was taken within the first 24h. The biopsies will be taken by a skilled
medical doctor. Some subjects may also report pain during the sampling of
muscle material.
DXA-scanning is a safe procedures, with no known health risk as long as none of
the exclusion criteria is met. The radiation dose emitted during a DXA-scan is
0.001 mSv. This is a very low exposure compared to the total background
radiation in The Netherlands, which is ~2.5 mSv/year. In total, subjects have
to come once for a screening and two times two days for measurements to the
MUMC.
P Debyelaan 25
Maastricht 6202 AZ
NL
P Debyelaan 25
Maastricht 6202 AZ
NL
Listed location countries
Age
Inclusion criteria
- COPD (GOLD I-IV);
- Current or ex-smoker;
- Age >18 years.
Exclusion criteria
- COPD patients planned for pulmonary rehabilitation or who recently participated in a rehabilitation program in the previous 6 months;
- Investigator*s uncertainty about willingness or ability of the patient to comply with the protocol requirements;
- Participation in any other study involving investigational exercise training, nutritional or pharmacological intervention;
- Oral glucocorticoid use;
- Recent exacerbation (<4 weeks) that required oral steroids and/or hospital admission;
- Subject is pregnant, planning to be pregnant during the study period, lactating, or women who consider themselves to be of childbearing potential and who are engaged in an active sex life and are unwilling to commit to the use of an approved form of contraception throughout the study period. The method of contraception must be recorded in the source documentation;
- Diabetes mellitus (type 1 and 2);
- Active cardiovascular disease or a cardiovascular event (such as myocardial infarction, cerebrovascular haemorrhage/infarction) in the previous 6 months;
- Recent major surgery;
- Thyroid dysfunction, current hepatic or renal disorders;
- Current malignancy (except for dermal malignancies);
- Central or obstructive sleep apnea;
- Current alcohol consumption > 20 grams alcohol/day;
- Intake of resveratrol containing dietary supplements;
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 |
|---|---|
| Other | ABR-49391 |
| CCMO | NL49391.068.14 |