Morphine to Maximize the Benefits of Exercise Training in COPD or ILD and Persistent Breathlessness

NCT03824834 | Unknown Phase 2

• 1 other identifier: MorEX_2019-5261
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to explore the role of low-dose immediate-release oral morphine as a novel adjunct pharmacotherapy to enable symptomatic adults with advanced chronic obstructive pulmonary disease (COPD) or interstitial lung disease (ILD) to exercise at higher intensities for longer durations and maximize the psycho-physiological benefits of a supervised exercise training program. We hypothesize that, compared to placebo, exercise training with oral morphine will result in relatively greater improvements in exercise endurance time and intensity ratings of perceived breathlessness during constant-load cardiopulmonary cycle exercise testing (CPET) at 75% of peak power output (PPO).

Conditions

Chronic Obstructive Pulmonary Disease; Interstitial Lung Disease

Keywords

Breathlessness; Dyspnea; Exercise; Opioids; Morphine; Exercise tolerance

Outcome Measures

Primary Outcomes (2)

• Cardiopulmonary exercise testing (CPET) endurance time

  Cardiopulmonary exercise testing (constant-load) will be used to assess change in endurance time pre to post intervention. Endurance time will be defined as the total duration of loaded pedalling (minutes).

  Immediately after exercise training program

• Borg modified 0-10 category ratio scale (Borg CR10) for breathlessness intensity

  Borg modified 0-10 category ratio scale (Borg CR10) will be used to assess breathlessness intensity during constant-load CPET at isotime, defined as the highest equivalent 2-min interval of exercise completed by a given participant during each of the constant-load CPETs.

  Immediately after exercise training program

Secondary Outcomes (11)

• Short Form Health Survey (SF-36) for quality of life

  Immediately after exercise training program

• Multidimensional Dyspnoea Profile for 'usual' breathlessness

  Immediately after exercise training program

• Hospital Anxiety and Depression Scale (HADS) for anxiety and depressive symptoms

  Immediately after exercise training program

• DEXA-derived body composition

  Immediately after exercise training program

• CPET physiological response (gas exchange)

  Immediately after exercise training program

Study Arms (2)

Exercise training with morphine

EXPERIMENTAL

Immediate-release oral morphine (syrup, 0.1 mg/kg body mass to a maximum dose of 10 mg) with supervised exercise training.

Drug: Exercise training with morphine

Exercise training with placebo

PLACEBO COMPARATOR

Placebo treatment with supervised exercise training.

Other: Exercise training with placebo

Interventions

Exercise training with morphine DRUG

Immediate-release oral morphine (syrup, 0.1 mg/kg body mass to a maximum dose of 10 mg) prepared in 250 mL of orange juice 30-min prior to each exercise session. Participants will complete exercise training sessions (three times per week for five weeks) on an electronically braked bike, supervised by a trained exercise specialist. Exercise sessions will be individualized based on participants' peak power output (60% PPO) determined from incremental exercise testing, and progressed to ensure the participant is exercising at a breathlessness intensity rating of between 3-5 Borg CR10 scale units and can complete at least 20-min of continuous cycling. Exercise duration will be increased in 5-min intervals up to 40-min. Thereafter, exercise intensity will be increased by 5-15% of baseline PPO.

Exercise training with morphine

Exercise training with placebo OTHER

Diluted simple syrup prepared in 250 mL of orange juice 30-min prior to each exercise session. Participants will complete exercise training sessions as per the experimental group.

Exercise training with placebo

Eligibility Criteria

• Age: 35 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males and females aged 35 years and over
• Clinical diagnosis of COPD or ILD
• Cigarette smoking history ≥20 years (COPD only)
• Post bronchodilator FEV1 \<50% predicted and FEV1/FVC \<0.70 (COPD only)
• Chronic breathlessness syndrome (modified Medical Research Council dyspnea score ≥3; Baseline Dyspnea Index focal score ≤6; and/or an Oxygen Cost Diagram rating ≤50% full scale despite optimal treatment of the underlying pathophysiology according to evidence-based clinical practice guidelines
• Report breathlessness as the main limiting factor to incremental CPET
• Body mass index \>18.5 kg/m2 and \<35 kg/m2

You may not qualify if:

• Changed respiratory medication dosage and/or frequency of administration in preceding two weeks
• Disease exacerbation/hospitalization in preceding six weeks
• Arterialized capillary CO2 tension (PacCO2) \>50 mmHg at rest
• Self-reported history of drug addiction and/or substance abuse assessed with the CAIG-aid and SISAP questionnaires
• Severe excessive daytime sleepiness assessed with the Epworth Sleepiness Scale (score of 16 out of 24)
• Currently use anti-seizure and/or opioid drug(s)
• Use daytime supplemental oxygen
• Exercise-induced oxyhemoglobin desaturation to \<80% on room air
• Participated in a pulmonary rehabilitation program in preceding 6 months
• Allergy/sensitivity to opioid drugs
• Significant extra-pulmonary disease that could impair exercise tolerance
• Contraindication(s) to cardiopulmonary exercise testing (e.g., significant cardiovascular, musculoskeletal, neurological disease)
• Pregnant or currently trying to become pregnant: women of child bearing potential (defined as having a menstrual period within the last 12 months) will be required to take a routine (urine) pregnancy test to rule out the possibility of pregnancy
• Self-report any of the following conditions: anemia or abnormally low blood volume; asthma; hypothyroidism; Addison's disease; renal insufficiency; hypopituitarism; severe malnutrition; digestive disease (any form of colitis disease); prostatic hypertrophy or urethral stricture
• Use of the blood thinning (anti-coagulant) drug Coumadin, Pradaxa, Xarelto and Eliquis in previous 2 weeks

Sponsors & Collaborators

• Dennis Jensen, Ph.D.: lead

Study Sites (1)

Montreal Chest Institute of the McGill University Health Center (MUHC)

Montreal, Quebec, H4A 3J1, Canada

RECRUITING

Related Links

• Clinical Exercise \& Respiratory Physiology Laboratory (CERPL) of McGill University

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Lung Diseases, Interstitial; Dyspnea; Motor Activity

Interventions

Exercise; Morphine

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Respiration Disorders; Signs and Symptoms, Respiratory; Signs and Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Morphine Derivatives; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Study Officials

• Dennis Jensen, Ph.D

  McGill University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Dennis Jensen, Ph.D

CONTACT

514-398-4184; denis.jensen@mcgill.ca

Hayley Lewthwaite, Ph.D

CONTACT

514-398-4184; hayley.lewthwaite@mail.mcgill.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Study medications, both morphine sulphate and placebo, will be dispensed by the research pharmacist according to the patient's randomization assignment. Neither research staff, nor patients, nor the treating physicians will be aware of the treatment assignment before or after randomization.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: January 28, 2019
• First Posted: January 31, 2019
• Study Start: August 6, 2019
• Primary Completion: June 1, 2020
• Study Completion: November 1, 2020
• Last Updated: August 16, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)