Leukocyte Function in Chronic Obstructive Pulmonary Disease (COPD)

• Sponsor: Imperial College London (Other)
• Overall Status: Completed
• CT.gov ID: NCT00147082
• Collaborator: (none)
• Enrollment: 100
• Location: 1
• Actual Duration (Months): 73.9
• Patients Per Site Per Month: 1.4

Study Details

Study Description

Brief Summary

The aim of this study is to investigate the mechanisms whereby leukocytes are recruited to the lung in chronic obstructive pulmonary disease (COPD) and cause tissue destruction. The hypothesis is that in COPD more leukocytes enter the lung and it is these cells that are responsible for the degradation of lung tissue. We, the researchers at Imperial College London, will isolate leukocytes from the blood of patients with COPD, healthy smokers and normal subjects and measure the movement of the leukocytes to chemoattractants. We will examine further, which cell surface receptors are responsible for this trafficking of cells. Furthermore, the differentiation of these cells in vitro will be compared with cells from healthy smokers and normal subjects. Specifically, the expression of enzymes that are responsible for tissue destruction and the cell surface receptors on these cells will be investigated. The objective is to identify the mechanisms whereby leukocytes from COPD patients behave differently to cells from healthy smokers and normal subjects with a view to identify novel targets for drug therapy.

Condition or Disease	Intervention/Treatment	Phase
COPD; Emphysema; Chronic Bronchitis

Detailed Description

Chemotaxis experiments will be performed in order to ascertain the migratory characteristics of leukocytes towards specific chemoattractants. Comparisons of cells from different subjects will be compared. In addition, the effects of various pharmaceutical interventions on this mechanism will also be addressed and compared within subject groups. In some experiments, cells will be differentiated in vitro and their cellular expression and regulation of inflammatory mediators and chemoattractants examined. Again comparisons will be made between subject groups and the efficacy of various pharmacological agents on these cells

Study Design

• Study Type: Observational
• Actual Enrollment: 100 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Leukocyte Migration and Differentiation in COPD Patients Compared to Healthy Smokers and Healthy Non-smoking Subjects.
• Actual Study Start Date: Feb 1, 2001
• Actual Primary Completion Date: Dec 1, 2004
• Actual Study Completion Date: Apr 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
COPD Patients with COPD - no intervention
Smokers without COPD Smokers without COPD - no intervention
Non-smokers Non-smokers with no history of respiratory disease - no intervention

Outcome Measures

Primary Outcome Measures

1. Effective Concentration (EC 50) of GRO Alpha [2 hours]

   Migration response of PBMC to Chemokine EC 50 represents the concentration of a drug that is required for 50% inhibition in vitro

2. Effective Concentration of IL-8 [2 hours]

   Migration response of PBMC to Chemokine EC 50 represents the concentration of a drug that is required for 50% inhibition in vitro

3. Effective Concentration of MCP-1 [2 hours]

   Migration response of PBMC to Chemokine

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Healthy Non-Smoking Subjects. All normal volunteers will meet the following criteria:

• Age 21-70 years.

• No history of respiratory or allergic disease.

• Normal baseline spirometry as predicted for age, sex and height.

• Non-smokers.

• No history of upper respiratory tract infection in the preceding six weeks.

• Not taking regular medication

• COPD Subjects. COPD is diagnosed according to American Thoracic Society, European Respiratory Society and British Thoracic Society guidelines. All COPD volunteers will meet the following criteria:

• Age between 40-75 years.

• A smoking history of at least 20 pack years. (1 pack year = 20 packs of cigarettes per day for 1 year)

• Forced expiratory volume at 1 second : Forced vital capacity (FEV1:FVC) ratio of <0.7, post-bronchodilator FEV1 of <85% predicted, reversibility with inhaled beta2-agonist of <15% of predicted FEV1: all three criteria are required.

• Current smokers or smokers who had ceased smoking for at least 6 months.

• No history of exacerbation, oral steroid or antibiotic use within the preceding 6 weeks.

• Normal serum alpha-1 antitrypsin level.

• No history of other respiratory or allergic disease.

• No evidence of atopy on skin prick testing to common aeroallergens (grass pollen, cat hair, house dust mite or Aspergillus fumigatus

• Healthy Smokers. All healthy smoking volunteers in trials will meet the following criteria:

• Age 21-70 years.

• Smoking history of at least 10 pack years. (1 pack year = 10 packs of cigarettes per day for 1 year).

• No history of respiratory or allergic disease.

• Normal baseline spirometry as predicted for age, sex and height.

• No history of upper respiratory tract infection in the preceding six weeks.

• Not taking regular medication.

Exclusion Criteria:

Subjects will not be included in this study if they meet any of the following exclusion criteria:

• Clinically significant findings in the medical history or on physical examination other than those of COPD in the COPD group.

• Pregnant women or mothers who are breastfeeding.

• Subjects who are unable to give informed consent.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Royal Brompton Hospital/NHLI Imperial College London	London		United Kingdom	SW3 6LY

Sponsors and Collaborators

• Imperial College London

Investigators

• Principal Investigator: Louise E Donnelly, PhD, Imperial College London

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Imperial College London
• ClinicalTrials.gov Identifier: NCT00147082
• Other Study ID Numbers: 01-024
• First Posted: Sep 7, 2005
• Last Update Posted: Dec 5, 2019
• Last Verified: Dec 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Imperial College London: chemokine; chemokine receptor; neutrophil; lymphocyte; monocyte
• Additional relevant MeSH terms: Bronchitis; Bronchitis, Chronic; Emphysema

Study Results

Participant Flow

Arm/Group Title	COPD	Smokers Without COPD	Non-smokers
Arm/Group Description	Patients with COPD - no intervention	Smokers without COPD - no intervention	Non-smokers with no history of respiratory disease - no intervention
Period Title: Overall Study
STARTED	37	33	30
COMPLETED	37	33	30
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	COPD	Smokers Without COPD	Non-smokers	Total
Arm/Group Description	Patients with COPD - no intervention	Smokers without COPD - no intervention	Non-smokers with no history of respiratory disease - no intervention	Total of all reporting groups
Overall Participants	37	33	30	100
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	65 (10)	40 (12)	34 (8)	47.45 (10)
Sex: Female, Male (Count of Participants)
Female	13 35.1%	15 45.5%	13 43.3%	41 41%
Male	24 64.9%	18 54.5%	17 56.7%	59 59%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (participants) [Number]
United Kingdom	37 100%	33 100%	30 100%	100 100%
Smoking History (pack/years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [pack/years]	48 (27)	21 (16)	0 (0)	24.7 (21)
FEV1 (% predicted) (% predicted) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [% predicted]	47 (15)	93 (21)	102 (14)	78.7 (17)

Outcome Measures

1. Primary Outcome

Title	Effective Concentration (EC 50) of GRO Alpha
Description	Migration response of PBMC to Chemokine EC 50 represents the concentration of a drug that is required for 50% inhibition in vitro
Time Frame	2 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	COPD	Smokers Without COPD	Non-smokers
Arm/Group Description	Patients with COPD - no intervention	Smokers without COPD - no intervention	Non-smokers with no history of respiratory disease - no intervention
Measure Participants	37	33	30
Mean (Standard Error) [ng/ml]	1.5 (0.9)	0.9 (0.2)	0.6 (0.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	COPD, Smokers Without COPD, Non-smokers
	Comments	p values were calculated
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.05
	Comments	The threshold for significance was p<0.05
	Method	Kruskal-Wallis
	Comments

2. Primary Outcome

Title	Effective Concentration of IL-8
Description	Migration response of PBMC to Chemokine EC 50 represents the concentration of a drug that is required for 50% inhibition in vitro
Time Frame	2 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	COPD	Smokers Without COPD	Non-smokers
Arm/Group Description	Patients with COPD - no intervention	Smokers without COPD - no intervention	Non-smokers with no history of respiratory disease - no intervention
Measure Participants	37	33	30
Mean (Standard Error) [ng/ml]	0.2 (0.1)	1.4 (0.4)	0.8 (0.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	COPD, Smokers Without COPD, Non-smokers
	Comments	p value was calculated
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.05
	Comments	The p value (<0.05) was the threshold for significance
	Method	Kruskal-Wallis
	Comments

3. Primary Outcome

Title	Effective Concentration of MCP-1
Description	Migration response of PBMC to Chemokine
Time Frame	2 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	COPD	Smokers Without COPD	Non-smokers
Arm/Group Description	Patients with COPD - no intervention	Smokers without COPD - no intervention	Non-smokers with no history of respiratory disease - no intervention
Measure Participants	37	33	30
Mean (Standard Error) [ng/ml]	0.5 (0.4)	0.2 (0.2)	0.3 (0.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	COPD, Smokers Without COPD, Non-smokers
	Comments	The p value was calculated
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.05
	Comments	The p value (<0.05) was the threshold for significance
	Method	Kruskal-Wallis
	Comments

Adverse Events

Time Frame	2 hours
Arm/Group Title	COPD		Smokers Without COPD		Non-smokers
Arm/Group Description	Patients with COPD - no intervention		Smokers without COPD - no intervention		Non-smokers with no history of respiratory disease - no intervention
All Cause Mortality
	COPD		Smokers Without COPD		Non-smokers
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/37 (0%)		0/33 (0%)		0/30 (0%)
Serious Adverse Events
	COPD		Smokers Without COPD		Non-smokers
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/37 (0%)		0/33 (0%)		0/30 (0%)
Other (Not Including Serious) Adverse Events
	COPD		Smokers Without COPD		Non-smokers
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/37 (0%)		0/33 (0%)		0/30 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.