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Report for Clinical Trial NCT02455362
Developed by Shray Alag, 2020.
SNP Clinical Trial Gene
A Multi-site, Double-blind, Parallel Arm, Block Randomised, Placebo Controlled, Factorial Phase III Study of Opioids for Chronic Refractory Breathlessness in People With Chronic Obstructive Pulmonary Disease.
Breathlessness, the sensation of breathing discomfort, is a major problem in people with chronic obstructive pulmonary disease (COPD). Breathlessness that persists despite optimal management of the underlying disease(s) is said to be refractory. Preliminary evidence suggests that a small, regular dose of morphine helps to reduce safely the sensation of breathlessness. However, this research on morphine for breathlessness has not defined the best way to adjust the dose of the medication, or refined which people are most likely to have benefit, no response or side effects. This is a randomized, double-blind phase III trial in people with COPD and significant refractory breathlessness, which will explore several important questions: - Are regular, low dose opioids (morphine) at four possible doses over 3 weeks more effective than placebo medication (containing no active ingredient) at improving breathlessness? - Does the medication have any effect on daily activity, breathlessness, and quality of life? - What are the common side effects of this intervention? - Does the benefit from the drug outweigh the side effects it produces? - Are there specific characteristics of people who are more likely to receive benefit from sustained release morphine? Participants will be allocated to receive three weeks of morphine sulfate (and laxative, docusate with senna), or placebo (and placebo laxative). The dose of morphine may be increased each week for weeks two and three. All medicines will appear the same (blinded) and neither the doctor nor the participant will know which medication the participant is receiving. Participants will have a medical interview, physical examination to collect some general health information, and baseline measurements including; daily activity, symptoms, and quality of life. A small amount of blood may be required to check eligibility. Further blood samples may be taken at week 1 and 3 to enable testing on how individuals respond to opioids, further consent will be obtained for these samples. Data on benefits, side effects, and medical care will be collected during comprehensive weekly visits. Participants will also fill out a simple diary twice daily for weeks one to three of the study, and for one day each week during an optional 3 month extension stage. The outcome of this study may enable better management of symptoms and activity in people COPD with medicines that are shown to be effective and safe.
NCT02455362 Chronic Obstructive Pulmonary Disease Dyspnea MeSH:Lung Diseases Lung Diseases, Obstructive Pulmonary Disease, Chronic Obstructive Dyspnea
HPO:Abnormal lung morphology Chronic obstructive pulmonary disease Dyspnea Obstructive lung disease Respiratory distress
2 Interventions
Name: Morphine sulfate
Name: Placebo
Primary Outcomes
Description: Rated on a 0-10 numerical rating scale (NRS) in a diary each evening. The primary endpoint is the difference between placebo, morphine sulfate 8 mg, or 16 mg after the first treatment week.
Measure: Change from baseline intensity of breathlessness over the previous 24 hours Time: Week 1Secondary Outcomes
Description: Rated on a 0-10 numerical rating scale (NRS) in a diary each evening.
Measure: Change from baseline unpleasantness of breathlessness over the previous 24 hours Time: Week 3Description: Rated on a 0-10 numerical rating scale (NRS) in a diary each morning.
Measure: Change from baseline intensity of breathlessness "right now" Time: Week 3Description: In addition to the NRS ratings, the intensity of breathlessness is rated on a 0-10 modified Borg scale in a evening diary.
Measure: Change from baseline in the intensity of breathlessness Time: Week 1Description: Collected in a diary in the evening, including of any rescue medication used.
Measure: Current medication use and compliance Time: At study end for up to 15 weeks.Description: Collected in a diary in the evening.
Measure: Number of participants with adverse events Time: At study end for up to 15 weeks.Description: Measured during two days at baseline and during at least five days of treatment week three.
Measure: Change from baseline physical activity using an accelerometer Time: Week 3Description: Measured using the revised Edmonton Symptoms Assessment Scale (ESAS-r).
Measure: Change from baseline in concurrent symptoms Time: Week 1Description: Measures the functional impact of breathlessness.
Measure: The modified Medical Research Council (mMRC) breathlessness scale Time: At study end for up to 15 weeks.Description: To explore whether longer term morphine treatment is associated with decreased levels of testosterone.
Measure: Change from baseline serum testosterone level Time: At the end of the 3 month follow-up stage, after up to 15 weeks.Description: From the baseline sample, the UGT2B7*2 and *28 polymorphisms, P-glycoprotein (ABCB1 5SNPs in a haplotype block), the 5-hydroxytryptamine type 3B (HTR3B) gene rs7103572, and mu opioid receptor (A118G) polymorphisms will be measured. Interleukin 1ß, TNFalpha and Il-6 will be measured at baseline and at the end of the first treatment week.
Measure: Change from baseline pharmacogenomic opioid blood profile Time: Week 1Description: In a subset of 55 participants, blood parameters for morphine and its metabolites will be analysed (4 blood samples over 8 hours) at steady state of the treatment at the end of the week 1.
Measure: Pharmacodynamic/-kinetic blood samples Time: Week 1Description: Exhaled gas measured using a non-invasive capnometer.
Measure: Change from baseline end-tidal carbon dioxide Time: Week 3Description: Non-invasive measurement of the oxygen saturation, respiratory rate, and heart rate.
Measure: Change from baseline pulse oximetry Time: Week 3Description: Twenty (20) participants at the Sydney and Adelaide sites will be invited to undertake a simple, non-invasive home sleep study using the ResMed ApneaLink Plus device.
Measure: Change from baseline sleep quality Time: The final night of week 3Description: Rated on a 4 point Likert scale in a morning diary.
Measure: Change from baseline sleep quality Time: During the study for up to 15 weeks.Description: The questionnaires used are the Epworth Sleepiness Scale, Leeds Sleep Questionnaire, and the Karolinska Sleepiness Scale.
Measure: Change from baseline sleep quality and sleep-related problems Time: Week 3Description: Measure of the bowel function, during treatment with placebo / morphine sulfate 8 or 16 mg.
Measure: Change from baseline bowel function index Time: Week 1Description: Measured on the CRQ-SAS Dyspnoea sub-scale.
Measure: Change from baseline breathlessness-related quality of life Time: Week 3Description: Measured using the EQ-5D questionnaire.
Measure: Change from baseline health-related quality of life Time: During the study for up to 15 weeks.Description: Life-Space is a measure of where a person goes, the frequency of going there, and the dependency in getting there.
Measure: Change from baseline Life-space Time: During the study for up to 15 weeks.Description: A score of 0 to 100 (in increments of 10) is assigned to participants based on their ability to undertake a range of daily tasks. The score gives an indication of the participant condition in terms of physical ability.
Measure: Change from baseline Australian Karnofsky Performance Status Time: During the study for up to 15 weeks.Description: A 14-item questionnaire used to measure anxiety and/or depression.
Measure: Change from baseline Hospital Anxiety and Depression Scale Time: Week 3Description: Participant-rated seven point scale of the perception of their change, specifically their improvement since the commencement of the study.
Measure: Global Impression of Change Time: During the study for up to 15 weeks.Description: Participants will be asked for their preference to continue at study exit ('Is this a therapy which, on balance, you would continue to take for your breathlessness?')
Measure: Blinded patient preference to continue treatment Time: At study end after up to 15 weeks.Description: Data on all health care contacts including lenght of hospitalizations, emergency department visits, DRG codes, outpatient visits to general practitioner and community nurse, and date of death.
Measure: Health economy composite Time: During the study for up to 15 weeks.Purpose: Treatment
Allocation: Randomized
Factorial Assignment
There is one SNP
SNPs
1 rs7103572
From the baseline sample, the UGT2B7*2 and *28 polymorphisms, P-glycoprotein (ABCB1 5SNPs in a haplotype block), the 5-hydroxytryptamine type 3B (HTR3B) gene rs7103572, and mu opioid receptor (A118G) polymorphisms will be measured.