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

Primary Purpose

COPD, COPD Exacerbation, COPD Exacerbation Acute

Status
Active
Phase
Phase 3
Locations
Uganda
Study Type
Interventional
Intervention
Theophylline ER
Placebo oral tablet
Standard of Care Treatment
Sponsored by
University of Miami
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for COPD focused on measuring Biomass Associated COPD, Low-dose Theophylline

Eligibility Criteria

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

Inclusion Criteria:

  1. Age ≥ 40 years
  2. Full-time resident of study area
  3. Post-bronchodilator FEV1/FVC < the lower limit of normal of the Global Lung Initiative Mixed Ethnic reference population
  4. Grade B-D COPD
  5. Daily biomass exposure

Exclusion Criteria:

  1. Plans to move within one year
  2. Uncontrolled hypertension
  3. Pregnancy (assessed by urine pregnancy test among women of childbearing age/menstrual history)
  4. Current use of chronic respiratory medications (Long acting Beta 2 Antagonists (LABA), Long-acting muscarinic antagonist (LAMA), inhaled corticosteroid (ICS))
  5. History of post-treatment pulmonary tuberculosis
  6. ≥10 pack year tobacco smoking history
  7. Known intolerance or contraindication to theophylline.

Sites / Locations

  • Makerere Lung Institute
  • Nakaseke Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Low-dose Theophylline Group

Placebo Group

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Change in forced expiratory volume in one second (FEV1)
FEV1 (L) as measured through spirometry
Change in forced vital capacity (FVC)
FVC (L) as measured through spirometry
Change in peak expiratory flow (PEF)
PEF (L/min) as measured through spirometry
Change in blood levels of high sensitivity C reactive protein (hs-CRP)
Blood levels of hs-CRP (mg/L)
Change in blood levels of fibrinogen
Blood levels of fibrinogen (mg/dL)
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.

Full Information

First Posted
June 10, 2019
Last Updated
October 19, 2023
Sponsor
University of Miami
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
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1. Study Identification

Unique Protocol Identification Number
NCT03984188
Brief Title
Effectiveness of Low-Dose Theophylline for the Management of Biomass-Associated COPD
Official Title
Effectiveness of Low-Dose Theophylline for the Management of Biomass-Associated COPD
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
February 23, 2021 (Actual)
Primary Completion Date
October 17, 2023 (Actual)
Study Completion Date
December 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Miami
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COPD, COPD Exacerbation, COPD Exacerbation Acute, Pollution Related Respiratory Disorder, Pollution; Exposure
Keywords
Biomass Associated COPD, Low-dose Theophylline

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
110 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Low-dose Theophylline Group
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo Group
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Theophylline ER
Other Intervention Name(s)
Low-dose Theophylline
Intervention Description
200 mg extended release (ER) low-dose theophylline taken orally daily
Intervention Type
Drug
Intervention Name(s)
Placebo oral tablet
Intervention Description
Manufactured methylcellulose placebo tablet taken orally daily
Intervention Type
Other
Intervention Name(s)
Standard of Care Treatment
Intervention Description
Per World Health Organization (WHO) guidelines for management of Chronic Obstructive Pulmonary Disease (COPD) treatment
Primary Outcome Measure Information:
Title
Change in St. George Respiratory Questionnaire (SGRQ) Scores
Description
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.
Time Frame
Baseline to 6 months, Baseline to 1 year
Secondary Outcome Measure Information:
Title
Change in forced expiratory volume in one second (FEV1)
Description
FEV1 (L) as measured through spirometry
Time Frame
Baseline to 6 months, Baseline to 1 year
Title
Change in forced vital capacity (FVC)
Description
FVC (L) as measured through spirometry
Time Frame
Baseline to 6 months, Baseline to 1 year
Title
Change in peak expiratory flow (PEF)
Description
PEF (L/min) as measured through spirometry
Time Frame
Baseline to 6 months, Baseline to 1 year
Title
Change in blood levels of high sensitivity C reactive protein (hs-CRP)
Description
Blood levels of hs-CRP (mg/L)
Time Frame
Baseline to 6 months, Baseline to 1 year
Title
Change in blood levels of fibrinogen
Description
Blood levels of fibrinogen (mg/dL)
Time Frame
Baseline to 6 months, Baseline to 1 year
Title
Change in Short Form 36 (SF-36) Questionnaire Scores
Description
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.
Time Frame
Baseline to 6 months, Baseline to 1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Trishul Siddharthan, MD
Organizational Affiliation
University of Miami
Official's Role
Principal Investigator
Facility Information:
Facility Name
Makerere Lung Institute
City
Kampala
Country
Uganda
Facility Name
Nakaseke Hospital
City
Nakaseke
Country
Uganda

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
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Effectiveness of Low-Dose Theophylline for the Management of Biomass-Associated COPD

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