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

COPD Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03984188
• Other study ID #: 20201523
• Secondary ID: 1K23HL146946-01I
• Status: Completed
• Phase: Phase 3
• Start date: February 23, 2021
• Est. completion date: December 15, 2023

Study information

• Verified date: December 2023
• Source: University of Miami
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: December 15, 2023
• Est. primary completion date: October 17, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• COPD
• COPD Exacerbation
• COPD Exacerbation Acute
• Pollution Related Respiratory Disorder
• Pollution; Exposure
• Pulmonary Disease, Chronic Obstructive
• Respiration Disorders
• Respiratory Tract Diseases

Intervention

Drug:
• Theophylline ER
200 mg extended release (ER) low-dose theophylline taken orally daily
• Placebo oral tablet
Manufactured methylcellulose placebo tablet taken orally daily

Other:
• Standard of Care Treatment
Per World Health Organization (WHO) guidelines for management of Chronic Obstructive Pulmonary Disease (COPD) treatment

Locations

Country	Name	City	State
Uganda	Makerere Lung Institute	Kampala
Uganda	Nakaseke Hospital	Nakaseke

Sponsors (2)

Lead Sponsor	Collaborator
University of Miami	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

Uganda, 

References & Publications (11)

Ait-Khaled N, Enarson D, Bousquet J. Chronic respiratory diseases in developing countries: the burden and strategies for prevention and management. Bull World Health Organ. 2001;79(10):971-9. Epub 2001 Nov 1. — View Citation

Barnes PJ. Theophylline in chronic obstructive pulmonary disease: new horizons. Proc Am Thorac Soc. 2005;2(4):334-9; discussion 340-1. doi: 10.1513/pats.200504-024SR. — View Citation

Beran D, Zar HJ, Perrin C, Menezes AM, Burney P; Forum of International Respiratory Societies working group collaboration. Burden of asthma and chronic obstructive pulmonary disease and access to essential medicines in low-income and middle-income countries. Lancet Respir Med. 2015 Feb;3(2):159-170. doi: 10.1016/S2213-2600(15)00004-1. — View Citation

Bonjour S, Adair-Rohani H, Wolf J, Bruce NG, Mehta S, Pruss-Ustun A, Lahiff M, Rehfuess EA, Mishra V, Smith KR. Solid fuel use for household cooking: country and regional estimates for 1980-2010. Environ Health Perspect. 2013 Jul;121(7):784-90. doi: 10.1289/ehp.1205987. Epub 2013 May 3. — View 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. — View Citation

Mendis S, Fukino K, Cameron A, Laing R, Filipe A Jr, Khatib O, Leowski J, Ewen M. The availability and affordability of selected essential medicines for chronic diseases in six low- and middle-income countries. Bull World Health Organ. 2007 Apr;85(4):279-88. doi: 10.2471/blt.06.033647. — View Citation

Moran-Mendoza O, Perez-Padilla JR, Salazar-Flores M, Vazquez-Alfaro F. Wood smoke-associated lung disease: a clinical, functional, radiological and pathological description. Int J Tuberc Lung Dis. 2008 Sep;12(9):1092-8. — View Citation

Perez-Padilla R, Ramirez-Venegas A, Sansores-Martinez R. Clinical Characteristics of Patients With Biomass Smoke-Associated COPD and Chronic Bronchitis, 2004-2014. Chronic Obstr Pulm Dis. 2014 May 6;1(1):23-32. doi: 10.15326/jcopdf.1.1.2013.0004. — View Citation

Rivera RM, Cosio MG, Ghezzo H, Salazar M, Perez-Padilla R. Comparison of lung morphology in COPD secondary to cigarette and biomass smoke. Int J Tuberc Lung Dis. 2008 Aug;12(8):972-7. — View Citation

Siddharthan T, Grigsby MR, Goodman D, Chowdhury M, Rubinstein A, Irazola V, Gutierrez L, Miranda JJ, Bernabe-Ortiz A, Alam D, Kirenga B, Jones R, van Gemert F, Wise RA, Checkley W. Association between Household Air Pollution Exposure and Chronic Obstructive Pulmonary Disease Outcomes in 13 Low- and Middle-Income Country Settings. Am J Respir Crit Care Med. 2018 Mar 1;197(5):611-620. doi: 10.1164/rccm.201709-1861OC. — View Citation

Zhou Y, Wang X, Zeng X, Qiu R, Xie J, Liu S, Zheng J, Zhong N, Ran P. Positive benefits of theophylline in a randomized, double-blind, parallel-group, placebo-controlled study of low-dose, slow-release theophylline in the treatment of COPD for 1 year. Respirology. 2006 Sep;11(5):603-10. doi: 10.1111/j.1440-1843.2006.00897.x. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Change in forced expiratory volume in one second (FEV1)	FEV1 (L) as measured through spirometry	Baseline to 6 months, Baseline to 1 year
Secondary	Change in forced vital capacity (FVC)	FVC (L) as measured through spirometry	Baseline to 6 months, Baseline to 1 year
Secondary	Change in peak expiratory flow (PEF)	PEF (L/min) as measured through spirometry	Baseline to 6 months, Baseline to 1 year
Secondary	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
Secondary	Change in blood levels of fibrinogen	Blood levels of fibrinogen (mg/dL)	Baseline to 6 months, Baseline to 1 year
Secondary	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