Idiopathic pulmonary fibrosis MedDRA version: 21.1 Level: PT Classification code 10021240 Term: Idiopathic pulmonary fibrosis System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Conditions
Interventions
Trade Name: Morphine Sulfate
Product Name: Morphine Sulfate
Pharmaceutical Form: Modified-release capsule, soft
INN or Proposed INN: morphine sulfate
Concentration unit: mg milligram(s)
Concentration
Sponsors
Royal Brompton and Harefield NHS Foundation Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Self-reported cough (> 8 weeks) with cough VAS = 30/100 2. A diagnosis of IPF within 5 years prior to the screening visit, as per applicable ATS/ERS/JRS/ALAT guidelines, in line with hospital records 3. Age 3.1 Male and female participants aged = 40 – 90 years at the time of signing informed consent 4. Sex: 4.1 Male participants: A male participant must agree to use contraception as detailed in Appendix 2 of this protocol during the study and for at least 90 days after the follow-up visit, and refrain from donating sperm during this period 4.2 Female participants: A female participant is eligible to participate if she is not pregnant, not breastfeeding, and not a woman of childbearing potential (WOCBP) as defined in Appendix 2. 5. Meeting all of the following criteria during the screening period: FVC = 45% predicted of normal, Forced expiratory volume in 1 second (FEV1)/FVC =0.7, DLCO corrected for Hb =30% predicted of normal. 6. The extent of fibrotic changes is greater than the extent of emphysema on the most recent HRCT scan (investigator determined within 24 months of the study screening visit). 7. Written informed consent. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 14 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
Exclusion criteria: ? 1. Treatment with immunosuppressive therapy or antibiotics within last 4 weeks of screening visit. A stable dose of corticosteroids equivalent to prednisolone of 10 mg per day or less, if used for an indication other than pulmonary disease will be permitted. 2. Current smoker 3. History of alcohol and drug(s) addiction 4. Regular use of sedative therapies 5. Acute IPF exacerbation within 6 months prior to screening and/or during the screening period. 6. Concurrent use of pirfenidone or Nintedanib, unless receiving a stable dose for at least 8 weeks prior to screening 7. Use of ACE inhibitors 8. Patients with co-existent conditions known to be associated with the development of fibrotic lung disease. This includes; connective tissue disease, suspected drug-induced lung disease, asbestosis or other asbestos related disease (pleural plaques, mesothelioma), granulomatous disease including sarcoidosis. Patients with an auto-immune profile considered diagnostic for a specific connective tissue disease will be excluded, even in the absence of systemic symptoms. Non-specific rises in auto antibodies e.g. rheumatoid factor, anti-nuclear antibody etc. will not be used to exclude individuals from the study. 9. Significant other organ co-morbidity including hepatic or renal impairment and pulmonary hypertension (investigator determined). 10. Significant coronary artery disease (myocardial infarction within 6 months or ongoing unstable angina within 4 weeks of screening visit) or congestive cardiac failure based on clinical examination 11. Patients at significant risk for side effects, intolerance or allergy to morphine 12. Pregnant and breastfeeding patients, or women of child-bearing potential, not using a reliable contraceptive method (see Appendix 2). A urine pregnancy test will be performed in females of child-bearing potential at the initial study visit. 13. Unable to provide informed written consent 14. Predicted life expectancy < 6 months 15. Use of long-term oxygen therapy. Use of ambulatory oxygen will be permitted. 16. Current or use of opiates within 14 days of the screening visit.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Does slow release morphine reduce the objective cough count in patients with Idiopathic pulmonary fibrosis?;Secondary Objective: 1. Does morphine reduce patient-reported cough? 2. Does morphine improve patient-reported quality of life? 3. Does morphine improve patient-reported breathlessness? ;Primary end point(s): Change in daytime cough frequency (coughs per hour) from baseline as assessed by objective digital cough monitoring at Day 14 of treatment.;Timepoint(s) of evaluation of this end point: Day 14 of intervention of either morphine sulphate or placebo. Washout of 7 days. Followed by another 14 days of crossover treatment and repeated evaluation. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): i) To evaluate the within subject differences in self-reported and objective cough frequency with morphine compared with placebo therapy. ii) To explore the relationships between quality of life, anxiety, dyspnoea and the response to morphine. iii) To explore the relationship between activity and cough and the response to morphine. iv) To evaluate a range of exploratory biomarkers for cough and response to Morphine Sulphate. ;Timepoint(s) of evaluation of this end point: Patients will be asked to attend a total of 6 visits, including the screening visit. Participants are expected to complete the study within 2-3 months of the screening visit. | — |
Countries
United Kingdom
Outcome results
None listed