Multiorgan Pathology in Chronic Obstructive Pulmonary Disease (COPD)

Chronic Obstructive Pulmonary Disease Clinical Trial

Official title:

COPD: Transition of Systemic Inflammation Into Multiorgan Pathology (Study 3). (De Effecten Van Ontsteking op Skeletspieren Bij COPD)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT00864994
• Other study ID #: 23475
• Status: Not yet recruiting
• Phase: N/A
• First received: March 18, 2009
• Last updated: March 26, 2010
• Start date: September 2010
• Est. completion date: April 2015

Study information

• Verified date: September 2010
• Source: Top Institute Pharma
• Contact: AMWJ Schols, Prof. dr. ir.
• Phone: +31 43 387 5046
• Email: a.schols[@]pul.unimaas.nl
• Is FDA regulated: No
• Health authority: Netherlands: Medical Ethics Review Committee (METC)
• Study type: Observational

Clinical Trial Summary

There is increasing evidence in the literature that COPD should not be considered as a localised pulmonary disorder but as a systemic disease involving pathology in several extra pulmonary tissues. Well characterized systemic features are a chronic low grade systemic inflammation, altered body composition and a skeletal muscle fibre type shift. There are indications that an absolute or relative increase of fat mass puts COPD patients at increased risk for cardiovascular pathology while muscle atrophy is associated with a high prevalence of osteoporosis and with impaired physical function. The origin of systemic inflammation is poorly understood. Both endogenous and exogenous risk factors contribute to systemic inflammation and extra-pulmonary manifestations of COPD.

Overall objective of study 3:

To compare the pattern and severity of the systemic inflammatory profile in relation to skeletal muscle weakness and cardiovascular risk profile in COPD patients with mild to moderate disease compared to non-susceptible smokers.

Specific objectives:

1. To study the relative contribution of pulmonary and extra pulmonary factors on exercise capacity, skeletal muscle function and health status

2. To relate diet, physical activity and cardiovascular risk factors to body composition, skeletal muscle function and exercise capacity status

3. To study the influence of the emphysema phenotype on extra pulmonary pathology in COPD

4. To study muscle fibre type size and composition and to relate muscle oxidative phenotype with insulin sensitivity, inflammation (local and systemic) and molecular signatures of oxidative energy and protein metabolism.

Study design:

Cross-sectional study. Healthy smoking subjects and COPD patients will undergo extensive clinical, metabolic and inflammatory assessment at the university clinics in Groningen, Maastricht and CIRO Horn.

Study population:

Totally 60 subjects will be included

• 30 healthy subjects who after 20 pack years smoking have no signs of COPD (age 40-75 years)

• 30 COPD patients with GOLD stage II (age 40-75 years)

Description:

Primary study parameters/outcome of the study:

1. Smoking history and behaviour, diet and physical activity level assessed by questionnaire

2. Extensive lung function and CT scanning of the lung, ECG

3. Candidate genes for muscle dysfunction and CVD risk

4. Body composition (BIA, waist-hip ratio, DEXA-scan)

5. Systemic inflammation

6. Advanced Glycosylated Endproduct (AGE)

7. Glucose tolerance test

8. Risk factors of metabolic syndrome

9. 6 minute walking distance

10. Handgrip strength

11. Skeletal muscle function by isokinetic dynamometry

12. Physical activity level and pattern by accelerometry

13. Muscle oxidative phenotype, fibre cross-sectional area and molecular signatures obtained in vastus lateralis muscle biopsies before and after incremental cycle ergometry

Nature and extent of the burden and risks associated with participation, benefit and group relatedness (if applicable):

• Totally 22 hours will be spend in the hospital during 3 visits

• CT-scanning of the lung is associated with a radiation burden of 0.8-1.6 mSv (dependent of body weight)

• 50 ml peripheral blood (v. cubiti)

• Muscle biopsy may be associated with temporary pain and haematoma

• Drawing of arterial blood from the radial artery rarely leads to bleeding and transitory nerve damage (numb feeling in wrist/hand area).

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 60
• Est. completion date: April 2015
• Est. primary completion date: April 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 40 Years to 75 Years

Eligibility

Inclusion Criteria:

• Age 40-75 years

• Age, pack years, FEV1/FVC and FEV1% predicted must fit in one of 2 groups of table 4.3

• Physically and mentally able to undergo the total study protocol

• Written informed consent

Exclusion Criteria:

• Participation in another study

• Alpha-1-antitrypsin deficiency

• Selected grade 1-3 co-morbidity listed in the ACE-27

• Active pulmonary infection like tuberculosis, pneumonia, flue, tracheobronchitis

• Active extra-pulmonary infection like hepatitis A-C, cystitis, gastroenteritis etc.

• Pulmonary diseases like sarcoidosis, IPF, silicosis, hypersensitivity pneumonitis, asthma

• Life threatening diseases like carcinoma, AIDS (including HIV+), acute leukemia etc.

• Medication that may affect the results of the study: NSAID's, immunosuppressive agents like prednisolon, methotrexate, azathioprine, sintrom tablets, askal

• Antibiotic or prednisolon use in the past 2 months

Study Design

Observational Model: Case Control, Time Perspective: Prospective

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Locations

Country	Name	City	State
Netherlands	Maastricht University Medical Center, Dept. of Respiratory Medicine	Maastricht	Limburg

Sponsors (8)

Lead Sponsor	Collaborator
Top Institute Pharma	AstraZeneca, Danone Institute International, GlaxoSmithKline, Maastricht University Medical Center, Nycomed, UMC Utrecht, University Medical Center Groningen

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Smoking history and behaviour, diet and physical activity level assessed by questionnaire			No
Primary	Extensive lung function and CT scanning of the lung, ECG			No
Primary	Candidate genes for muscle dysfunction and CVD risk			No
Primary	Body composition			No
Primary	Systemic inflammation			No
Primary	Advanced Glycosylated Endproduct (AGE)			No
Primary	Glucose Tolerance Test			No
Primary	Risk factors of metabolic syndrome			No
Primary	6 minutes walking distance			No
Primary	Handgrip strength			No
Primary	Skeletal muscle function by isokinetic dynamometry			No
Primary	Physical activity level and pattern by accelerometry			No
Primary	Muscle oxidative phenotype, fibre cross-sectional area and molecular signatures obtained in vastus lateralis muscle biopsies before and after incremental cycle ergometry			No