To assess whether ingestion of dietary nitrate in the form of NaNO3 solution is able to improve metabolic efficiency and exercise training compared to a NaCl solution placebo. A secondary objective will be to gain more insight in potential…
ID
Source
Brief title
Condition
- Bronchial disorders (excl neoplasms)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary parameter is metabolic efficiency during submaximal cycle ergometry
tests (before and after 7 days of ingestion of both NaNO3 solution and NaCl
placebo).
Metabolic efficiency will be calculated with the following equation:
Metabolic efficiency = (load (W) of exercise * 0.01433 (kcal*min-1) / (energy
expenditure during exercise * REE)(kcal*min-1)*100%
Secondary outcome
Secondary parameters are bloodpressure, dyspnea, cycle endurance time, Oxygen
uptake during rest and exercise, body temperature, blood markers (e.g. lactate,
IFABP as a marker for intestinal damage and cardiac troponin as a marker for
myocardial injury) . These parameters will be measured at 4 times (before and
after 7 days of ingestion of both NaNO3 solution and NaCl placebo).
Background summary
COPD patients often suffer from physical incapacity and metabolic efficiency.
Although exercise training is effective in improving exercise performance,
their metabolic capacity may further benefit from nutritional enhancement of
exercise training. Recent work in humans suggests that increasing nitric oxide
(NO) bioavailability may induce physiological changes beyond the well known
hemodynamic effects. NO is an important systemic and pulmonary arterial
vasodilator. Within the human body, exogenous nitrate (NO3-) is reduced to
bioactive nitrite (NO2-) by facultative anaerobic bacteria in the saliva and
further to NO via various pathways. NO synthesis is compromised in patients
with stable COPD. Dietary nitrate may be effective in upregulating whole body
NO synthesis in COPD.
Study objective
To assess whether ingestion of dietary nitrate in the form of NaNO3 solution is
able to improve metabolic efficiency and exercise training compared to a NaCl
solution placebo. A secondary objective will be to gain more insight in
potential mechanisms of putative positive effects of nitrate supplementation by
investigating bio markers of muscle oxidative metabolism, intestinal function
and myocardial injury.
Study design
Double-blind, randomized cross-over placebo controlled proof of concept study.
Intervention
Each subject will consume (in a randomized fashion) both the intervention
beverage (NaNO3 solution: 7x ~140 mL; 7x ~8 mmol NO3-1)) and the placebo (NaCl
solution: 7x ~140 mL), separated by a 1 wk washout period.
Study burden and risks
Subjects will perform 8 measurements (4 resting energy expenditure + 4
submaximal cycle tests) during 4 test days. During these test days, a small
teflon catheter will be inserted into a forearm vein with the assistance of a
small needle for periodical blood collection, which is subsequently removed.
The discomfort of this procedure is transient and is very similar to having an
injection by a needle, or when donating blood. Once the needle is removed there
should be no sensation from the catheter. Some minor discomfort may occur and a
small hematoma may result. For the submaximal cycle ergometry tests, the
potential risks and discomforts inherent to the exercise testing procedure
during each visit are minimal and are similar to those associated with any form
of strenuous physical activity including fatigue, transient abnormal blood
pressure etc.
The dose of NaNO3 used in the current study has been administered in multiple
clinical and exercise studies. No adverse events were reported, except for
reports of mild headache (which may or may not be associated with the sodium
nitrate). The long term effects of nitrate ingestion still need to be fully
investigated. The use of nitrate rich food has however been described to
occasionally lead to mild gastro intestinal distress (bloating, belching).
P Debyelaan 25
Maastricht 6202 AZ
NL
P Debyelaan 25
Maastricht 6202 AZ
NL
Listed location countries
Age
Inclusion criteria
1) COPD according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines.
2) Peak VO2 / peak load > 10 ml/min/W, as a indication for metabolic inefficiency, determined using CPET data available from the assessment.
Exclusion criteria
- Sodium intake limitation
- Long-term oxygen therapy, because of the methodology that is used to measure oxygen uptake and ventilation
- Severe renal impairment (GFR < 30 ml/min), because nitrate is excreted mainly by the kidneys and thus depends on the patient*s renal function.
- Use of medications that might develop a risk for hypotension in combination with nitrate: PDE-5 inhibitors (sildenafil, tadaladil, verdanefil), nitrate-containing/releasing medication (glyceryl trinitrate, isosorbide dinitrate, isosorbide mononitrate, nitroprusside). The medical doctor will screen the prescibed medications during the baseline assessment, but the investigator will verify which medication are used by the patient in question during the recruitment and just before start with the intervention;
- Contra-indications for performing (sub)maximal cycle ergometry during the baseline assessment preceding the rehabilitation program.
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-47701 |
| CCMO | NL47701.068.14 |