Prevalence of Different Haptoglobin Phenotypes in Patients With COPD- Frequent Exacerbators Versus Non Exacerbators

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified December 2012 by Carmel Medical Center
Sponsor:
Collaborator:
Technion, Israel Institute of Technology
Information provided by (Responsible Party):
Michal Steinberg, Carmel Medical Center
ClinicalTrials.gov Identifier:
NCT01745419
First received: December 5, 2012
Last updated: December 19, 2012
Last verified: December 2012
  Purpose

Chronic obstructive pulmonary disease (COPD) is a common disease in smokers. COPD has a slowly deteriorating course, punctuated by exacerbations- acute events characterized by increasing shortness of breath and putrid sputum. Exacerbations of COPD may be precipitated by several factors, most commonly infections.

Exacerbation frequency generally increases with declining lung function. However, some patients with COPD consistently experience a higher rate of exacerbations than others despite similar severity of COPD. This has led researchers to postulate the existence of a distinct subgroup of "frequent exacerbators" . Recent work has also brought attention to a subset of patients who experience remarkably few exacerbations despite significantly impaired lung function. Careful characterization of both of these extreme subgroups of COPD may offer additional insights into why certain patients are prone to frequent exacerbations while others remain relatively protected.

Haptoglobin (Hp) is a protein produced predominately by the liver . In humans two types of genes for Hp exist (1 and 2) with possible combinations of these two genes- 1-1, 1-2, or 2-2. The Hp 2 gene is believed to have arisen from the Hp 1 gene in human evolution. Subsequently the prevalence of the Hp 2 allele has spread throughout the world, probably as a result of its ability to provide a selective advantage against infectious disease. The Hp 1-2 combination is a very common one. In most western countries, the prevalence of the Hp genotypes is 16% Hp 1-1, 36% Hp 2-2 and 48% Hp 2-1.

The Hp gene form has been shown to be associated with disease. Specifically, Hp phenotypes have been found to affect propensity to atherosclerosis in Diabetic individuals. There have been several studies suggesting that the Hp 2-2 phenotype is associated with a protection against infectious complications.

In view of the importance of respiratory infections on COPD exacerbations, and of the gained knowledge of Haptoglobin subtypes on propensity to infection, we propose to investigate whether Haptoglobin subtypes are in correlation with the "frequent exacerbator" phenotype of COPD. We postulate that, since people with Hp 1-1 are more prone to infection, the frequency of the Hp 1-1 phenotype will be higher in "frequent exacerbators" of COPD than in "non- exacerbators".

To test our hypothesis we propose to determine Hp phenotype in two groups of COPD patients: one with frequent exacerbations and one with no exacerbations, and compare the relative frequency of the 1-1 phenotype in the two groups.


Condition
Pulmonary Disease, Chronic Obstructive

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Retrospective
Official Title: Prevalence of Different Haptoglobin Phenotypes in Patients With COPD- Frequent Exacerbators Versus Non Exacerbators

Resource links provided by NLM:


Further study details as provided by Carmel Medical Center:

Primary Outcome Measures:
  • Prevalence of Hp 1-1 phenotype [ Time Frame: 1 visit- approximately 2 hours. ] [ Designated as safety issue: No ]
    Prevalence as percentage of Hp 1-1 phenotypes in each group of patients


Biospecimen Retention:   Samples Without DNA

3 ml of Serum will be collected from each patient


Estimated Enrollment: 100
Study Start Date: March 2013
Estimated Study Completion Date: March 2017
Estimated Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Groups/Cohorts
COPD Frequent Exacerbators
COPD patients having experienced at least two episodes of acute exacerbations in the former 12 months. (Acute exacerbations are defined as worsening symptoms requiring treatment with systemic steroids (oral or parenteral) or antibiotics, a visit to the emergency room, and/or admission to a hospital. Events separated by at least 21 days are considered as separate events of exacerbation.)
COPD non- exacerbators
COPD patients who have not experienced exacerbations in the former 24 months. (Acute exacerbations are defined as worsening symptoms requiring treatment with systemic steroids (oral or parenteral) or antibiotics, a visit to the emergency room, and/or admission to a hospital. Events separated by at least 21 days are considered as separate events of exacerbation.)

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   40 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

Patients with COPD

Criteria

Inclusion Criteria:

  1. Patients diagnosed with COPD according to GOLD guidelines1
  2. Age 40-100 years
  3. Smoking history of > 10 pack - years
  4. Spirometry consistent with airflow obstruction (FEV1/FVC ratio < 70%)
  5. Moderate to severe airflow obstruction (FEV1<60%)
  6. At least two episodes of acute exacerbations in the former 12 months, or no exacerbations in the former 24 months. (Acute exacerbations are defined as worsening symptoms requiring treatment with systemic steroids (oral or parenteral) or antibiotics, a visit to the emergency room, and/or admission to a hospital. Events separated by at least 21 days are considered as separate events of exacerbation.)

Exclusion Criteria:

Patients with a history of any of the following conditions will be excluded from the study:

  1. Active Tuberculosis
  2. Pulmonary fibrosis or Asbestosis
  3. Organ transplantation
  4. Lung volume reduction surgery
  5. Previous lung or lobe resection.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01745419

Contacts
Contact: Michal Shteinberg, MD, PhD 972-4-8250517 michal.shteinberg@gmail.com
Contact: Yochai Adir, MD 972-4-8250517 yochaiad@clalit.org.il

Locations
Israel
Pulmonology Institute, Carmel Medical Center Not yet recruiting
Haifa, Israel, 34362
Contact: Michal Shteinberg, MD, PhD       michal.shteinberg@gmail.com   
Sub-Investigator: Yochai Adir, MD         
Sub-Investigator: Anat Amital, MD         
Principal Investigator: Michal Shteinberg, MD, PhD         
Sub-Investigator: Assaf Jacobi, MD         
Pulmonology Institute, Carmel Medical Center Not yet recruiting
Haifa, Israel, 34362
Contact: Michal Shteinberg, MD PhD       michal.shteinberg@gmail.com   
Sponsors and Collaborators
Carmel Medical Center
Technion, Israel Institute of Technology
Investigators
Principal Investigator: Michal Shteinberg, MD, PhD Pulmonology Institute, Carmel Medical Center
  More Information

No publications provided

Responsible Party: Michal Steinberg, Dr. Michal Shteinberg, MD, PhD, Carmel Medical Center
ClinicalTrials.gov Identifier: NCT01745419     History of Changes
Other Study ID Numbers: CMC-12-0121-CTIL
Study First Received: December 5, 2012
Last Updated: December 19, 2012
Health Authority: Israel: Ministry of Health

Keywords provided by Carmel Medical Center:
COPD
Exacerbation
Haptoglobin

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

ClinicalTrials.gov processed this record on September 18, 2014