Sustained-release oral morphine to alleviate persistent dyspnea in patients with chronic respiratory insufficiency due to amyotrophic lateral sclerosis outside the administration of ventilatory assistance: prospective multicenter randomized, placebo-controlled study, parallel arms (OPIDYS-ALS).

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Paris

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08], Diseases [C] - Musculoskeletal Diseases [C05]

Decision date (initial)

2026-02-13

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

The primary objective is to show that oral sustained-release morphine reduces the unpleasantness of the worst episode of dyspnea experienced during a given day, four weeks after inclusion in the study.

Secondary objectives 2

1. 1) to show that oral sustained-release morphine: a) reduces: • the intensity of dyspnea unpleasantness measured at a fixed point in the day (after 1 hour of unassisted breathing), four weeks after inclusion; • the time dynamics of dyspnea unpleasantness (mean, worst, fixed points...) over the duration of the study, as determined from daily measures, according to the principle of ecological momentary assessment [62]; • the intensity of dyspnea-related anxiety at various time points ; • the ratings of dyspnea sensory and affective dimensions as assessed from a reference multidimensional questionnaire (Multidimensional Dyspnea Profile); • the intensity of pain; • the intensity of dyspnea-related anxiety in the patients' closest relatives; • the burden of care on the patients' closest relatives. b) improves: • health-related quality of life; • the general sense of well-being; • the quality of sleep; • the quality of life of the patients' closest relatives.
2. 2) and to assess: • treatment respiratory tolerance; • treatment general tolerance.

Conditions and MedDRA coding

patients with chronic respiratory insufficiency due to amyotrophic lateral sclerosis.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. age over 18 ;
2. known diagnosis of amyotrophic lateral sclerosis irrespective of the clinical form of the disease, its severity and its progression;
3. chronic respiratory insufficiency with home nocturnal non-invasive mask ventilation established for at least 6 hours per night since 3 months or more (no upper limit);
4. self-report of dyspnea while breathing unassisted during the day (i.e outside nocturnal ventilation), either at rest or for minimal efforts, with a rating of 2 or more on a dyspnea unpleasantness numerical rating scale;
5. affiliation to a social security regime (patients on "aide médicale d'état" will not be included);
6. ability to understand participants' information;
7. prior signing of informed consent .

Exclusion criteria 23

1. Woman of childbearing potential, unless they are using reliable methods of contraception stable for a minimum of 2 months prior to first administration and willing to use it for the entire duration of the study and for one month after the last dosing.
2. known severe hepatocellular insufficiency (with encephalopathy)
3. known uncontrolled epilepsy
4. swallowing difficulties severe enough to prevent the oral administration of drugs
5. participation in another interventional clinical trial evaluating a health product or any randomized clinical trial
6. under legal protection measure (tutorship or curatorship) and patient deprived of freedom
7. prior diagnosis of concurrent chronic respiratory disease, such as asthma, chronic obstructive pulmonary disease or restrictive lung disease; this criterion will be appreciated by the investigator from the participants medical charts and no further diagnostic procedure will be required;
8. episode of acute respiratory deterioration resolved less than 3 weeks before inclusion;
9. Hypercapnia associated with an arterial blood pH below 7.38
10. Conditions with increased potential for gastrointestinal perforation
11. Clinically important disruptions of the blood-brain barrier
12. permanent dependency on ventilatory assistance (more than 20 hours a day);
13. Myocardial infarction within the past 6 months
14. Patients treated with strong CYP3A4 inducers (e.g. carbamazepine, rifampin, St. John’s Wort)
15. History of opioid abuse
16. presence of a tracheostomy;
17. inability to read and understand the rating scales and questionnaires correctly; the inability to personally fill scoring forms in not a non-inclusion criterion if a caregiver is identified and can provide for this action;
18. known contraindications to the administration of morphine or other opioids (Acute or severe respiratory depression, acute bronchial asthma, paralytic ileus, gastrointestinal obstruction, coma, severe central nervous system depression, known hypersensitivity to morphine or other opioids, acute alcohol intoxication, concomitant use of monoamine oxidase inhibitors or within 14 days of their discontinuation, head injury, raised intracranial pressure, acute abdomen, severe hepatic impairment, severe renal impairment, uncontrolled seizures, delirium tremens, severe hypotension, shock, biliary colic, pancreatitis, pregnancy at or near term, breastfeeding, inability to swallow or risk of aspiration, use in opioid-naïve patients at high doses)
19. another indication for the administration of morphine
20. known contraindications to the administration of naloxegol ((Known or suspected gastrointestinal obstruction, risk of recurrent gastrointestinal obstruction, hypersensitivity to naloxegol or excipients, concomitant use of strong CYP3A4 inhibitors (Ketoconazole, itraconazole, posaconazole, voriconazole, clarithromycin, telithromycin, ritonavir, cobicistat, indinavir, nelfinavir, saquinavir, atazanavir, nefazodone, boceprevir, telaprevir, grapefruit juice) severe hepatic impairment (Child–Pugh class C)
21. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption.
22. known renal insufficiency at inclusion time (confirmed by the last biology by a creatinine clearance < 30 ml/min calculated with the Cockcroft-Gault formula)
23. Women who are pregnant, breastfeeding, or plan to become pregnant while in the trial.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint of the study will be the change in intensity of dyspnea unpleasantness during the worst dyspneic episode experienced in the previous 24 hours, assessed at Day 7 and four weeks after inclusion in the study

Secondary endpoints 4

1. Endpoints evaluating the efficacy of the treatment on dyspnea: The change in the intensity of dyspnea unpleasantness NRS evaluation, The evolution of dyspnea unpleasantness, The description of dyspnea according to the "Dyspnea ALS-15, The multidimensional description of dyspnea according to the Multidimensional Dyspnea Profile (MDP), The intensity of dyspnea-related anxiety evaluated on a 0-10 NRS, The time spent daily under mechanical ventilation (mechanical ventilator recordings),
2. Endpoints evaluating the efficacy of the treatment on outcomes other than dyspnea and on quality of life, The intensity of pain evaluated on a 0-10 NRS, Health-related quality of life (HRQoL), evaluated,in a general manner, using the 12-Item Short-Form Health Survey (SF12) , Sleep quality evaluated using the Pittsburgh Sleep Quality Index (PSQI)
3. Endpoints evaluating the impact of the treatment on the patients' closest informal caregiver: The intensity of general anxiety evaluated on a 0-10 NRS, The intensity of dyspnea-related anxiety evaluated on a 0-10 NRS, The intensity of the burden of care weighing on the patients' designated closest relatives, if any, using the revised 22-item Zarit Burden Interview (ZBI), The quality of life of the patients' designated closest relatives, if any, using the questionnaire (WHOQOL-BREF).
4. Endpoints evaluating the tolerance of the treatment : The incidence of adverse events will be evaluated during each interaction with the graded according to CTCAE, . respiratory frequency during unassisted breathing, transcutaneous pulsed oxygen saturation during unassisted breathing, and arterial blood gases during unassisted breathing, Opioid-induced constipation. Opioid-induced constipation will be assessed as a predefined secondary endpoint related to treatment tolerance

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

Sponsor organisation

Assistance Publique Hopitaux De Paris

Address

Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux

City

Paris Cedex 10

Postcode

75475

Country

France

Scientific contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

thomas SIMILOWSKI

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

thomas SIMILOWSKI

Locations

1 EU/EEA country · 6 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 25 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications