Regulation of muscle oxidative phenotype by hypoxia in Chronic Obstructive Pulmonary Disease (COPD) and Chronic Heart Failure (CHF)

Regulation of muscle oxidative phenotype by hypoxia in Chronic Obstructive Pulmonary Disease and Chronic Heart Failure

Status

Active, not recruiting

Phases

Unknown

Study type

Observational

Source

NL-OMON

Registry ID

NL-OMON26311

Enrollment

Registered

2008-08-11

Start date

2008-10-01

Completion date

Unknown

Last updated

2024-02-28

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

COPD, chronic heart failure hypoxemia, skeletal muscle dysfunction

Interventions

In this cross-sectional study, muscle biopsies will be obtained before and after exercise and tested for molecular markers of hypoxia. All subjects will be characterized thoroughly including measureme

Eligibility

Inclusion criteria

Inclusion criteria: 1. COPD patients: COPD according to GOLD criteria. 2. CHF patients: diagnosis heart failure with an ejection fraction <40% determined by echocardiography; 3. Healthy persons.

Exclusion criteria

Exclusion criteria: COPD patients: malignancy, cardiac failure, distal arteriopathy, recent surgery, severe endocrine, hepatic or renal disorders, oxygen therapy and recent participation in a revalidation program (previous 6 months). CHF patients: unstable disease, unstable angina pectoris, correctable cause of heart failure or valvular heart disease, restrictive or hypertrophic cardiomyopathy, malignancy, pulmonary disease (including primary pulmonary hypertension and COPD), distal arteriopathy, recent surgery, severe endocrine, hepatic or renal disorders and recent participation in a revalidation program (previous 6 months).

Design outcomes

Primary

Measure	Time frame
1. Main outcome parameters are the expression levels of HIF-1á, PGC-1 and PPARs (before and after exercise), which will be measured at protein and mRNA level by western blotting and PCR respectively; 2. Also, markers of hypoxia such as vascular endothelial growth factor (VEGF), carbonic anhydrase-9 (CA-9) and heme oxygenase-1 (HO-1) will be investigated using real time PCR; 3. Beside this, metabolic enzyme activities (citrate synthase, â-hydroxyacyl-CoA dehydrogenase, phosphofructokinase) and muscle fiber type proportions will be determined to assess muscle oxidative phenotype; 4. Main outcomes in the adipose tissue biopsies comprise of adipocyte size, gene expression levels of inflammatory and hypoxia-related genes and adipose tissue macrophage infiltration.	—

Measure

Time frame

1. Main outcome parameters are the expression levels of HIF-1á, PGC-1 and PPARs (before and after exercise), which will be measured at protein and mRNA level by western blotting and PCR respectively; 2. Also, markers of hypoxia such as vascular endothelial growth factor (VEGF), carbonic anhydrase-9 (CA-9) and heme oxygenase-1 (HO-1) will be investigated using real time PCR; 3. Beside this, metabolic enzyme activities (citrate synthase, â-hydroxyacyl-CoA dehydrogenase, phosphofructokinase) and muscle fiber type proportions will be determined to assess muscle oxidative phenotype; 4. Main outcomes in the adipose tissue biopsies comprise of adipocyte size, gene expression levels of inflammatory and hypoxia-related genes and adipose tissue macrophage infiltration.

—

Secondary

Measure	Time frame
Secondary outcome parameters are skeletal muscle function and exercise capacity.	—

Contacts

Public ContactB. Borst, van den

b.vdborst@maastrichtuniversity.nl+31 (0)43 3881327

Outcome results

None listed

Source: NL-OMON (via WHO ICTRP)