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Multiorgan Pathology in Chronic Obstructive Pulmonary Disease (COPD)

This study is not yet open for participant recruitment.
Verified September 2010 by Top Institute Pharma
Sponsor:
Collaborators:
University Medical Centre Groningen
Maastricht University Medical Center
UMC Utrecht
Danone Institute International
GlaxoSmithKline
Nycomed: A Takeda Company
AstraZeneca
Information provided by:
Top Institute Pharma
ClinicalTrials.gov Identifier:
NCT00864994
First received: March 18, 2009
Last updated: March 26, 2010
Last verified: September 2010
History of Changes
  Purpose

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)

Condition
Chronic Obstructive Pulmonary Disease

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Prospective
Official Title: COPD: Transition of Systemic Inflammation Into Multiorgan Pathology (Study 3). (De Effecten Van Ontsteking op Skeletspieren Bij COPD)

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Top Institute Pharma:

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

Biospecimen Retention:   Samples With DNA

Blood will be retained to investigate differences in candidate genes (SNPs) for COPD and CVD between the different groups.


Estimated Enrollment: 60
Study Start Date: September 2010
Estimated Study Completion Date: April 2015
Estimated Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Groups/Cohorts
1
• 30 healthy subjects with 20 pack years smoking who have no signs of COPD (age 40-75 years)
2
• 30 COPD patients with GOLD stage II (age 40-75 years)

Detailed 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).
  Eligibility

Ages Eligible for Study:   40 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

Totally 60 subjects will be included

  • 30 healthy subjects with 20 pack years smoking who have no signs of COPD (age 40-75 years)
  • 30 COPD patients with GOLD stage II (age 40-75 years)
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00864994

Contacts
Contact: AMWJ Schols, Prof. dr. ir. +31 43 387 5046 a.schols@pul.unimaas.nl

Locations
Netherlands
Maastricht University Medical Center, Dept. of Respiratory Medicine Not yet recruiting
Maastricht, Limburg, Netherlands, 6200 MD
Contact: Annemie Schols, Prof. dr. ir.     +31 43 387 50 46     a.schols@pul.unimaas.nl    
Principal Investigator: Emiel Wouters, Prof. dr. MD            
Sponsors and Collaborators
Top Institute Pharma
University Medical Centre Groningen
Maastricht University Medical Center
UMC Utrecht
Danone Institute International
GlaxoSmithKline
Nycomed: A Takeda Company
AstraZeneca
Investigators
Principal Investigator: Emiel Wouters, Prof. dr. MD Maastricht University Medical Center, Dept. of Respiratory Medicine
  More Information

No publications provided

Responsible Party: Schols, Prof. dr. ir. AMWJ., Maastricht University Medical Center, Dept. of Respiratory Medicine
ClinicalTrials.gov Identifier: NCT00864994     History of Changes
Other Study ID Numbers: 23475
Study First Received: March 18, 2009
Last Updated: March 26, 2010
Health Authority: Netherlands: Medical Ethics Review Committee (METC)

Keywords provided by Top Institute Pharma:
COPD
Inflammation
Smoking
Multiorgan pathology
Extra pulmonary manifestations

Additional relevant MeSH terms:
Inflammation
Lung Diseases
Respiration Disorders
Pulmonary Disease, Chronic Obstructive
 Lung Diseases, Obstructive
Pathologic Processes
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on June 18, 2013