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).

Trial details

Who runs it

Assistance Publique Hopitaux De Paris

Trial code

EU 2025-522546-52-00

Record updated

2026. február 13.

Original description

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.Read full original descriptionShow less

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).

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.

Inclusion: age over 18 ; known diagnosis of amyotrophic lateral sclerosis irrespective of the clinical form of the disease, its severity and its progression; 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); 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; affiliation to a social security regime (patients on "aide médicale d'état" will not be included); ability to understand participants' information; prior signing of informed consent .

Exclusion: 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; Patients treated with strong CYP3A4 inducers (e.g. carbamazepine, rifampin, St. John’s Wort); 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); 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); swallowing difficulties severe enough to prevent the oral administration of drugs; 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; episode of acute respiratory deterioration resolved less than 3 weeks before inclusion; Conditions with increased potential for gastrointestinal perforation; Myocardial infarction within the past 6 months; History of opioid abuse; known severe hepatocellular insufficiency (with encephalopathy); known uncontrolled epilepsy; Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption; known renal insufficiency at inclusion time (confirmed by the last biology by a creatinine clearance < 30 ml/min calculated with the Cockcroft-Gault formula); Clinically important disruptions of the blood-brain barrier; permanent dependency on ventilatory assistance (more than 20 hours a day); presence of a tracheostomy; 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; another indication for the administration of morphine; Women who are pregnant, breastfeeding, or plan to become pregnant while in the trial; participation in another interventional clinical trial evaluating a health product or any randomized clinical trial; under legal protection measure (tutorship or curatorship) and patient deprived of freedom; Hypercapnia associated with an arterial blood pH below 7.38.

EU CTIS 2025-522546-52-00