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Enhancement of in−Vitro GC Function in Patients With COPD

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00241631
Recruitment Status : Completed
First Posted : October 19, 2005
Results First Posted : December 4, 2019
Last Update Posted : December 4, 2019
Sponsor:
Collaborators:
Mitsubishi Tanabe Pharma Corporation
Medical Research Council
Information provided by (Responsible Party):
Imperial College London

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.

Condition or disease Intervention/treatment Phase
COPD Drug: Fluticasone Propionate Drug: placebo Drug: Theophylline Phase 2

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).

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 49 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : April 2006
Actual Primary Completion Date : August 2007
Actual Study Completion Date : August 2007

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Placebo Comparator: Placebo
Inhaled Theophylline placebo capsule, then placebo, then active Theophylline
Drug: placebo
Drug: Theophylline
Theophylline placebo capcule

Active Comparator: Steroid
Inhaled Theophylline placebo capsule, then Fluticasone Propionate 500 ug bid, then active Theophylline
Drug: Fluticasone Propionate
500 u

Drug: Theophylline
Theophylline placebo capcule




Primary Outcome Measures :
  1. Sputum Inflammatory Cell Counts [ Time Frame: 10 weeks ]
    Supernatant collect, cell pellets count on slides


Secondary Outcome Measures :
  1. Interleukin 8 (IL8) [ Time Frame: 10 weeks ]
    Interleukin 8 (IL8) assessed from sputum

  2. Total Sputum Eosinophils [ Time Frame: 10 weeks ]
    Total eosinophils cells assessed from sputum



Information from the National Library of Medicine

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Ages Eligible for Study:   40 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00241631


Locations
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United Kingdom
Windsor chest clinic KEVII Hospital
Windsor, Berks, United Kingdom, SL4 3DP
Sponsors and Collaborators
Imperial College London
Mitsubishi Tanabe Pharma Corporation
Medical Research Council
Investigators
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Principal Investigator: ian adcock, PhD Imperial College London

Publications of Results:
Other Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Imperial College London
ClinicalTrials.gov Identifier: NCT00241631    
Other Study ID Numbers: mitHDAC#1
First Posted: October 19, 2005    Key Record Dates
Results First Posted: December 4, 2019
Last Update Posted: December 4, 2019
Last Verified: November 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Imperial College London:
COPD
Additional relevant MeSH terms:
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Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Lung Diseases
Respiratory Tract Diseases
Fluticasone
Theophylline
Anti-Inflammatory Agents
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Dermatologic Agents
Anti-Allergic Agents
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Vasodilator Agents
Purinergic P1 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents