Effectiveness of Low-Dose Theophylline for the Management of Biomass-Associated COPD

Study Overview
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Brief Summary
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Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death worldwide, and over 90% of COPD-related deaths occurring in low- and middle-income countries (LMICs). Household air pollution (HAP) - from burning solid fuels such as wood, dung, agricultural crop waste, and coal for energy - is the primary risk factor for COPD in these settings. Biomass-related COPD has a distinct histopathology, phenotype and inflammatory profile when compared to tobacco mediated COPD. Despite the high global burden of biomass-related disease, little is known about the effectiveness of pharmacotherapies for biomass-related COPD; to date, no clinical trials have focused specifically on treatment of biomass-related COPD. This study proposes to assess the health impact of biomass-related COPD and test the effectiveness of low dose theophylline compared to standard therapy among adults with biomass-related COPD in Uganda with the aim to assess whether low-dose theophylline improves respiratory symptoms, decreases the inflammatory profile of serum biomarkers and whether administration attenuates the effect of HAP on lung function. The study additionally aims to assess whether low-dose theophylline is a cost-effective intervention based on the incremental cost-effectiveness ratio and a range of willingness to pay thresholds.

Official Title
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Effectiveness of Low-Dose Theophylline for the Management of Biomass-Associated COPD

Conditions
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COPD, COPD Exacerbation Acute, Pollution Related Respiratory Disorder, Pollution; Exposure, COPD Exacerbation

Intervention / Treatment
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* Drug: Theophylline ER
* Drug: Placebo oral tablet
* Other: Standard of Care Treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 40 years Full-time resident of study area Post-bronchodilator FEV1/FVC < the lower limit of normal of the Global Lung Initiative Mixed Ethnic reference population Grade B-D COPD Daily biomass exposure Exclusion Criteria: Plans to move within one year Uncontrolled hypertension Pregnancy (assessed by urine pregnancy test among women of childbearing age/menstrual history) Current use of chronic respiratory medications (Long acting Beta 2 Antagonists (LABA), Long-acting muscarinic antagonist (LAMA), inhaled corticosteroid (ICS)) History of post-treatment pulmonary tuberculosis ≥10 pack year tobacco smoking history Known intolerance or contraindication to theophylline.

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low-dose Theophylline Group<br>Participant in this group will receive low-dose theophylline in addition to standard care, per World Health Organization (WHO) guidelines for management of Chronic Obstructive Pulmonary Disease (COPD) treatment, over a one year period. | Drug: Theophylline ER<br>* 200 mg extended release (ER) low-dose theophylline taken orally daily<br>* Other names: Low-dose Theophylline;Other: Standard of Care Treatment<br>* Per World Health Organization (WHO) guidelines for management of Chronic Obstructive Pulmonary Disease (COPD) treatment<br>|
| Placebo Comparator: Placebo Group<br>Participant in this group will receive a placebo in addition to standard care, per World Health Organization (WHO) guidelines for management of Chronic Obstructive Pulmonary Disease (COPD) treatment. | Drug: Placebo oral tablet<br>* Manufactured methylcellulose placebo tablet taken orally daily<br>Other: Standard of Care Treatment<br>* Per World Health Organization (WHO) guidelines for management of Chronic Obstructive Pulmonary Disease (COPD) treatment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in St. George Respiratory Questionnaire (SGRQ) Scores | The SGRQ comprises of 50 items and consists of two parts. The first part pertains to symptoms and the second pertains to functional status as well as social and psychological impact of disease. Overall scores ranges between 0 and 100 with higher scores indicating more limitations. | Baseline to 6 months, Baseline to 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in forced expiratory volume in one second (FEV1) | FEV1 (L) as measured through spirometry | Baseline to 6 months, Baseline to 1 year | 
| Change in forced vital capacity (FVC) | FVC (L) as measured through spirometry | Baseline to 6 months, Baseline to 1 year | 
| Change in peak expiratory flow (PEF) | PEF (L/min) as measured through spirometry | Baseline to 6 months, Baseline to 1 year | 
| Change in blood levels of high sensitivity C reactive protein (hs-CRP) | Blood levels of hs-CRP (mg/L) | Baseline to 6 months, Baseline to 1 year | 
| Change in blood levels of fibrinogen | Blood levels of fibrinogen (mg/dL) | Baseline to 6 months, Baseline to 1 year | 
| Change in Short Form 36 (SF-36) Questionnaire Scores | The SF-36 consists of eight scaled domains (vitality, physical functioning, body pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning, mental health) each transformed into a 0-100 scale. Lower scores signify higher levels of disability. | Baseline to 6 months, Baseline to 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Biomass Associated COPD, Low-dose Theophylline