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Enhancement of in-Vitro GC Function in Patients With COPD

Primary Purpose

COPD

Status
Completed
Phase
Phase 2
Locations
United Kingdom
Study Type
Interventional
Intervention
Fluticasone Propionate
placebo
Theophylline
Sponsored by
Imperial College London
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for COPD focused on measuring COPD

Eligibility Criteria

40 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:Participants with COPD with an FEV1 of 80-30% predicted. This will incorporate the majority of participants with COPD seen within the chest clinic. Patients with an FEV1 > 80% predicted are not generally severe enough to warrant hospital follow up. These patients are also unlikely to have severe enough disease (and therefore airway inflammation) which may be modified by the therapeutic agents we are studying. Patients with an FEV1 < 30% tend to have more severe symptom limitation and generally (though not always) find participation in a clinical trial involving 4 visits to the clinic difficult. Their airway disease is also generally less responsive to therapeutic intervention and as a consequence finding measurements which show changes to these therapeutic interventions is more difficult. COPD patients All participants will be classified to Stage 2-3 of the GOLD (Global initiative for Obstructive Lung Disease) guidelines Male or female, aged 45-80 years (according to GOLD guidelines) 30% < FEV1 < 80% predicted FEV1/FVC < 70% Cigarette exposure of >10 pack-years# With or without chronic symptoms (cough, sputum production, dyspnea). Steroid therapy will be stopped before run-in, but long acting bronchodilators are acceptable. The participants are able to give informed consent # The smoking history should include both the number smoked, for how long, and an estimate of total pack-years of smoking. One pack of 20 cigarettes smoked per day for 1 year = one pack year. Total pack years = No. cigarettes smoked per day/20 x no. years of smoking Exclusion Criteria: Any history or evidence of asthma Pregnancy, breast-feeding or planned pregnancy during the study. Fertile women not using acceptable contraceptive measures, as judged by the investigator Hospital admission with respiratory infection within the last 6 months Upper respiratory infection within the last 4 weeks Participants who have received research medication within the previous one month Participants unable to give informed consent Any mental condition rendering the participant unable to understand the nature, scope and possible consequences of the study Known or suspected hypersensitivity to study therapy or excipients Participants with significant or unstable ischemic heart disease, arrhythmia, cardiomyopathy, heart failure, uncontrolled hypertension as defined by the investigator, or any other relevant cardiovascular disorder as judged by the investigator Any current respiratory tract disorders other than COPD, which is considered by the investigator to be clinically significant Any significant disease or disorder (e.g. gastrointestinal, liver, renal, neurological, musculoskeletal, endocrine, metabolic, malignant, psychiatric, major physical impairment) or abnormality laboratory tests which, in the opinion of the investigator, may either put the participant at risk because of inclusion in the study, or may influence the results of the study, or the participants ability to take part in the study

Sites / Locations

  • Windsor chest clinic KEVII Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Active Comparator

Arm Label

Placebo

Steroid

Arm Description

Inhaled Theophylline placebo capsule, then placebo, then active Theophylline

Inhaled Theophylline placebo capsule, then Fluticasone Propionate 500 ug bid, then active Theophylline

Outcomes

Primary Outcome Measures

Sputum Inflammatory Cell Counts
Supernatant collect, cell pellets count on slides

Secondary Outcome Measures

Interleukin 8 (IL8)
Interleukin 8 (IL8) assessed from sputum
Total Sputum Eosinophils
Total eosinophils cells assessed from sputum

Full Information

First Posted
October 18, 2005
Last Updated
November 15, 2019
Sponsor
Imperial College London
Collaborators
Mitsubishi Tanabe Pharma Corporation, Medical Research Council
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1. Study Identification

Unique Protocol Identification Number
NCT00241631
Brief Title
Enhancement of in-Vitro GC Function in Patients With COPD
Official Title
Enhancement of In-vitro GC Function in Patients With COPD. A Randomised, Double Blind, Placebo Controlled, Parallel-group Study to Investigate the Effect of Theophylline and Fluticasone on Induced Sputum Cells Obtained Form COPD Patients
Study Type
Interventional

2. Study Status

Record Verification Date
November 2019
Overall Recruitment Status
Completed
Study Start Date
April 2006 (Actual)
Primary Completion Date
August 2007 (Actual)
Study Completion Date
August 2007 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Imperial College London
Collaborators
Mitsubishi Tanabe Pharma Corporation, Medical Research Council

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The investigator wish therefore to continue these studies on theophylline principally by conducting a small clinical pilot study on 20-30 COPD patients in a randomised, double-blind, placebo-controlled, parallel-group study.
Detailed Description
The global burden of COPD - a common and debilitating chronic inflammatory disease that is characterised by the progressive development of airflow limitation (shortness of breath - SOB) and is poorly reversible with currently available drugs -is increasing. Cigarette smoking is strongly linked with the ongoing inflammation; inflammation that can continue even when the patient has stopped smoking. The severity of airflow limitation (SOB) is correlated with the degree of pulmonary (lung) inflammation. Histone deacetylases (HDACs)are important molecules in suppressing this pulmonary inflammation. We have recently shown that patients with COPD have a reduction in total HDAC which correlates with the severity of their lung disease. Corticosteroids (anti-inflammatory treatment) act, at least in part, by recruitment of these HDACs to the site of active inflammatory gene transcription (which reduces the production of inflammatory molecules) and are widely used in COPD in patients with severe disease. Unfortunately, in COPD, inhaled corticosteroids seem to have little effect on the underlying inflammation (though in a selective group of patients with COPD they do reduce the number of infections a patient may have by a small amount). Theophylline has been used in the treatment of asthma and COPD for over 70 years, but its use has recently declined. Data so far obtained in primary cells (cells from patients used in the laboratory) from COPD patients suggests that low dose theophylline (~5mg/l) should be effective in restoring steroid sensitivity in patients with COPD (and hence reduce inflammation thus improving SOB).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COPD
Keywords
COPD

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
49 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Inhaled Theophylline placebo capsule, then placebo, then active Theophylline
Arm Title
Steroid
Arm Type
Active Comparator
Arm Description
Inhaled Theophylline placebo capsule, then Fluticasone Propionate 500 ug bid, then active Theophylline
Intervention Type
Drug
Intervention Name(s)
Fluticasone Propionate
Intervention Description
500 u
Intervention Type
Drug
Intervention Name(s)
placebo
Intervention Type
Drug
Intervention Name(s)
Theophylline
Intervention Description
Theophylline placebo capcule
Primary Outcome Measure Information:
Title
Sputum Inflammatory Cell Counts
Description
Supernatant collect, cell pellets count on slides
Time Frame
10 weeks
Secondary Outcome Measure Information:
Title
Interleukin 8 (IL8)
Description
Interleukin 8 (IL8) assessed from sputum
Time Frame
10 weeks
Title
Total Sputum Eosinophils
Description
Total eosinophils cells assessed from sputum
Time Frame
10 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:Participants with COPD with an FEV1 of 80-30% predicted. This will incorporate the majority of participants with COPD seen within the chest clinic. Patients with an FEV1 > 80% predicted are not generally severe enough to warrant hospital follow up. These patients are also unlikely to have severe enough disease (and therefore airway inflammation) which may be modified by the therapeutic agents we are studying. Patients with an FEV1 < 30% tend to have more severe symptom limitation and generally (though not always) find participation in a clinical trial involving 4 visits to the clinic difficult. Their airway disease is also generally less responsive to therapeutic intervention and as a consequence finding measurements which show changes to these therapeutic interventions is more difficult. COPD patients All participants will be classified to Stage 2-3 of the GOLD (Global initiative for Obstructive Lung Disease) guidelines Male or female, aged 45-80 years (according to GOLD guidelines) 30% < FEV1 < 80% predicted FEV1/FVC < 70% Cigarette exposure of >10 pack-years# With or without chronic symptoms (cough, sputum production, dyspnea). Steroid therapy will be stopped before run-in, but long acting bronchodilators are acceptable. The participants are able to give informed consent # The smoking history should include both the number smoked, for how long, and an estimate of total pack-years of smoking. One pack of 20 cigarettes smoked per day for 1 year = one pack year. Total pack years = No. cigarettes smoked per day/20 x no. years of smoking Exclusion Criteria: Any history or evidence of asthma Pregnancy, breast-feeding or planned pregnancy during the study. Fertile women not using acceptable contraceptive measures, as judged by the investigator Hospital admission with respiratory infection within the last 6 months Upper respiratory infection within the last 4 weeks Participants who have received research medication within the previous one month Participants unable to give informed consent Any mental condition rendering the participant unable to understand the nature, scope and possible consequences of the study Known or suspected hypersensitivity to study therapy or excipients Participants with significant or unstable ischemic heart disease, arrhythmia, cardiomyopathy, heart failure, uncontrolled hypertension as defined by the investigator, or any other relevant cardiovascular disorder as judged by the investigator Any current respiratory tract disorders other than COPD, which is considered by the investigator to be clinically significant Any significant disease or disorder (e.g. gastrointestinal, liver, renal, neurological, musculoskeletal, endocrine, metabolic, malignant, psychiatric, major physical impairment) or abnormality laboratory tests which, in the opinion of the investigator, may either put the participant at risk because of inclusion in the study, or may influence the results of the study, or the participants ability to take part in the study
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
ian adcock, PhD
Organizational Affiliation
Imperial College London
Official's Role
Principal Investigator
Facility Information:
Facility Name
Windsor chest clinic KEVII Hospital
City
Windsor
State/Province
Berks
ZIP/Postal Code
SL4 3DP
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
15888697
Citation
Ito K, Ito M, Elliott WM, Cosio B, Caramori G, Kon OM, Barczyk A, Hayashi S, Adcock IM, Hogg JC, Barnes PJ. Decreased histone deacetylase activity in chronic obstructive pulmonary disease. N Engl J Med. 2005 May 12;352(19):1967-76. doi: 10.1056/NEJMoa041892.
Results Reference
background
PubMed Identifier
20299628
Citation
Ford PA, Durham AL, Russell RE, Gordon F, Adcock IM, Barnes PJ. Treatment effects of low-dose theophylline combined with an inhaled corticosteroid in COPD. Chest. 2010 Jun;137(6):1338-44. doi: 10.1378/chest.09-2363. Epub 2010 Mar 18.
Results Reference
result
PubMed Identifier
24525446
Citation
Kirkham PA, Whiteman M, Winyard PG, Caramori G, Gordon F, Ford PA, Barnes PJ, Adcock IM, Chung KF. Impact of theophylline/corticosteroid combination therapy on sputum hydrogen sulfide levels in patients with COPD. Eur Respir J. 2014 May;43(5):1504-6. doi: 10.1183/09031936.00131513. Epub 2014 Feb 13. No abstract available.
Results Reference
derived

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Enhancement of in-Vitro GC Function in Patients With COPD

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