The Impact of Anemia of Chronic Disease on Chronic Obstructive Pulmonary Disease Patients - Full Text View

Sponsor:	Aristotle University Of Thessaloniki
Information provided by:	Aristotle University Of Thessaloniki
ClinicalTrials.gov Identifier:	NCT01033175

Purpose

Hypothesis:

The first part of the study is a survey on the prevalence of anemia of chronic disease (ACD) among COPD patients. The 2nd and 3rd part will test 2 null hypotheses (Ho): 1.serum inflammatory markers and plasma erythropoietin do not differ between COPD patients with and without ACD and 2. exercise capacity does not differ between COPD patients with and without ACD.

Rationale-Aim:

ACD is an immune driven disorder, developing in subjects suffering from chronic inflammatory diseases. COPD is a disorder very likely to be associated to ACD due to its systemic inflammatory dimension. Currently, data on the prevalence of ACD and on the level of inflammatory markers which are implicated in the pathogenesis of ACD in COPD subjects are limited and controversial. Furthermore, there is no data on the effect of ACD on exercise capacity of COPD subjects.

Based to the aforementioned, this study has three goals:

to determine the prevalence and the epidemiologic characteristics of ACD in a population of clinical stable COPD patients
to investigate whether the levels of serum inflammatory markers and of plasma erythropoietin differ between COPD patients with ACD and without ACD
to determine potential differences regarding the aerobic exercise capacity between these two groups, using the cardiopulmonary exercise testing (CPET).

Condition	Intervention
Anemia COPD	Procedure: maximal cardiopulmonary exercise testing Procedure: peripheral blood samples

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Screening
Official Title:	The Clinical Impact of Anemia of Chronic Disease on Chronic Obstructive Pulmonary Disease Patients

Resource links provided by NLM:

MedlinePlus related topics: Anemia COPD (Chronic Obstructive Pulmonary Disease) Coping with Chronic Illness Exercise and Physical Fitness

U.S. FDA Resources

Further study details as provided by Aristotle University Of Thessaloniki:

Primary Outcome Measures:

The primary outcome measure is peak oxygen uptake (VO2 peak, ml/kg/min) during maximal cardiopulmonary exercise testing and whether it differs between patients with ACD and COPD and patients with COPD without ACD. [ Time Frame: Within 15 days from enrollment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Serum levels of inflammatory markers [ Time Frame: Within 15 days from enrollment ] [ Designated as safety issue: No ]
Erythropoietin [ Time Frame: Within 15 days from enrollment ] [ Designated as safety issue: No ]
MRC dyspnea scale [ Time Frame: Within 15 days from enrollment ] [ Designated as safety issue: No ]
The rest cardiopulmonary exercise testing parameters [ Time Frame: Within 15 days from enrollment ] [ Designated as safety issue: No ]

Estimated Enrollment:	60
Study Start Date:	December 2009
Study Completion Date:	June 2010
Primary Completion Date:	May 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
COPD patients with ACD In the 1st part of this clinical study the prevalence ACD in COPD subjects will be estimated in a consecutive population of COPD subjects who will visit the hospital's pulmonary clinics as outpatients. During the first visit, subjects will give a detailed medical history and will undergo clinical examination and pulmonary function testing 15 minutes post-bronchodilation. Eligible patients will then undergo peripheral venous blood analysis. The first 30 COPD subjects from the population described above, fulfilling the criteria of ACD will constitute the first arm (group of "cases").ACD is defined by low Hb levels (men: <13 mg/dl, women: <12 mg/dl), no other cause of anemia present, normal or increased serum ferritin and decreased total iron binding capacity.	Procedure: maximal cardiopulmonary exercise testing Cardiopulmonary exercise testing (CPET) will be performed on a cyclic ergometer with continuous monitoring of a 12-lead electrocardiogram, heart rate and blood pressure. While breathing with a mask, the patients will perform a ramp protocol which includes 2-minutes free pedaling and progressive increase of power by 10, 15 or 20 watts/minute; power size will be selected after considering the patient' s daily activity and parameters of pulmonary function. CPET will be performed until exhaustion, unless the subjects reveal symptoms or signs indicating the exercise should stop (e.g. severe breathlessness). Procedure: peripheral blood samples Peripheral venous blood samples will be collected again in the morning after a fasting period of ≥12 hours. After immediate centrifugation, aliquots will be stored at -75˚C until analysis. Inflammatory markers and erythropoietin will be analyzed by flow cytometry and by enzyme-linked immunosorbent assay, using commercially available kits.
COPD patients without ACD Thirty matched patients with COPD without ACD from the initial cohort will constitute the second arm (the "controls")	Procedure: maximal cardiopulmonary exercise testing Cardiopulmonary exercise testing (CPET) will be performed on a cyclic ergometer with continuous monitoring of a 12-lead electrocardiogram, heart rate and blood pressure. While breathing with a mask, the patients will perform a ramp protocol which includes 2-minutes free pedaling and progressive increase of power by 10, 15 or 20 watts/minute; power size will be selected after considering the patient' s daily activity and parameters of pulmonary function. CPET will be performed until exhaustion, unless the subjects reveal symptoms or signs indicating the exercise should stop (e.g. severe breathlessness). Procedure: peripheral blood samples Peripheral venous blood samples will be collected again in the morning after a fasting period of ≥12 hours. After immediate centrifugation, aliquots will be stored at -75˚C until analysis. Inflammatory markers and erythropoietin will be analyzed by flow cytometry and by enzyme-linked immunosorbent assay, using commercially available kits.

Arms

Assigned Interventions

COPD patients with ACD

In the 1st part of this clinical study the prevalence ACD in COPD subjects will be estimated in a consecutive population of COPD subjects who will visit the hospital's pulmonary clinics as outpatients. During the first visit, subjects will give a detailed medical history and will undergo clinical examination and pulmonary function testing 15 minutes post-bronchodilation. Eligible patients will then undergo peripheral venous blood analysis. The first 30 COPD subjects from the population described above, fulfilling the criteria of ACD will constitute the first arm (group of "cases").ACD is defined by low Hb levels (men: <13 mg/dl, women: <12 mg/dl), no other cause of anemia present, normal or increased serum ferritin and decreased total iron binding capacity.

Procedure: maximal cardiopulmonary exercise testing

Cardiopulmonary exercise testing (CPET) will be performed on a cyclic ergometer with continuous monitoring of a 12-lead electrocardiogram, heart rate and blood pressure. While breathing with a mask, the patients will perform a ramp protocol which includes 2-minutes free pedaling and progressive increase of power by 10, 15 or 20 watts/minute; power size will be selected after considering the patient' s daily activity and parameters of pulmonary function. CPET will be performed until exhaustion, unless the subjects reveal symptoms or signs indicating the exercise should stop (e.g. severe breathlessness).

Procedure: peripheral blood samples

Peripheral venous blood samples will be collected again in the morning after a fasting period of ≥12 hours. After immediate centrifugation, aliquots will be stored at -75˚C until analysis. Inflammatory markers and erythropoietin will be analyzed by flow cytometry and by enzyme-linked immunosorbent assay, using commercially available kits.

COPD patients without ACD

Thirty matched patients with COPD without ACD from the initial cohort will constitute the second arm (the "controls")

Procedure: maximal cardiopulmonary exercise testing

Cardiopulmonary exercise testing (CPET) will be performed on a cyclic ergometer with continuous monitoring of a 12-lead electrocardiogram, heart rate and blood pressure. While breathing with a mask, the patients will perform a ramp protocol which includes 2-minutes free pedaling and progressive increase of power by 10, 15 or 20 watts/minute; power size will be selected after considering the patient' s daily activity and parameters of pulmonary function. CPET will be performed until exhaustion, unless the subjects reveal symptoms or signs indicating the exercise should stop (e.g. severe breathlessness).

Procedure: peripheral blood samples

Peripheral venous blood samples will be collected again in the morning after a fasting period of ≥12 hours. After immediate centrifugation, aliquots will be stored at -75˚C until analysis. Inflammatory markers and erythropoietin will be analyzed by flow cytometry and by enzyme-linked immunosorbent assay, using commercially available kits.

Eligibility

Ages Eligible for Study:	40 Years to 85 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

1st part of the study:
- COPD clinically stable (patients with post-bronchodilation FEV1/FVC <0.7 and no acute exacerbations, hospital admissions or treatment changes in the last 3 months).
- 2nd and 3rd part:
- As above.

Exclusion Criteria:

1st part of the study:
- history of asthma,
- history of respiratory infection in the last 3 months
2nd and 3rd part: As above and additionally:
- history of malignancy or haematologic disorder
- acute or chronic inflammatory disease
- systematic or autoimmune disorder
- thyroid disease
- liver cirrhosis
- heart failure (ejection fraction <55%)
- history of gastrointestinal or other hemorrhage
- renal failure (GFR<60 ml/min/1.73m2)
- blood transfusion in the last 4 months
- administration of cortisone in the last month
- pregnancy
- mental impairment
- medical conditions which are contraindications to exercise testing, such as:
acute myocardial infarction (in the last 6 months)
unstable angina
left main coronary stenosis or its equivalent
syncope
symptomatic severe aortic stenosis or other moderate stenotic valvular disease
uncontrolled arrhythmias causing symptoms
acute pulmonary embolus or pulmonary infarction
thrombosis of lower extremities
suspected dissecting aneurysm
pulmonary oedema
room air desaturation at rest <85%
severe untreated arterial hypertension at rest (>200 mmHg systolic, >120 mmHg diastolic)
high degree atrioventricular block
hypertrophic cardiomyopathy and
orthopedic impairment that compromises exercise performance

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01033175

Locations

Greece
Respiratory Failure Unit, General Hospital "G. Papanikolaou"
Thessaloniki, Greece, 57010
Department of Pulmonology, Aristotle University of Thessaloniki
Thessaloniki, Greece, 57010

Sponsors and Collaborators

Aristotle University Of Thessaloniki

Investigators

Principal Investigator:

Paraskevi Argyropoulou, MD, Prof

Aristotle University Of Thessaloniki

More Information

Publications:

Weiss G, Goodnough LT. Anemia of chronic disease. N Engl J Med. 2005 Mar 10;352(10):1011-23. Review. No abstract available.

[No authors listed] Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease. American Thoracic Society. Am J Respir Crit Care Med. 1995 Nov;152(5 Pt 2):S77-121. Review. No abstract available.

American Thoracic Society; American College of Chest Physicians. ATS/ACCP Statement on cardiopulmonary exercise testing. Am J Respir Crit Care Med. 2003 Jan 15;167(2):211-77. Review. No abstract available. Erratum in: Am J Respir Crit Care Med. 2003 May 15;1451-2.

Responsible Party:	Paraskevi Argyropoulou, Professor of Pulmonology, Aristotle University of Thessaloniki
ClinicalTrials.gov Identifier:	NCT01033175 History of Changes
Other Study ID Numbers:	8/22.1.08
Study First Received:	December 15, 2009
Last Updated:	July 6, 2010
Health Authority:	Greece: Ethics Committee

Keywords provided by Aristotle University Of Thessaloniki:

COPD
anemia
exercise
cytokines
erythropoietin

Additional relevant MeSH terms:

Anemia
Chronic Disease
Lung Diseases
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive

Hematologic Diseases
Disease Attributes
Pathologic Processes
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on February 09, 2012