Clinical trial NCT04145674: A Proof of Concept, Phase 2, Double-blind, Randomized Trial With d-Methadone Product Versus Placebo
Official title: A Proof of Concept, Multicentre, Phase 2, Double-Blind, Randomized, Placebo-Controlled Study on the Efficacy, Safety and Tolerability of d-Methadone in Moderate to Very Severe Restless Legs Syndrome With Periodic Limb Movements: the Glu-REST Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Restless Legs Syndrome
Lead sponsor: Ente Ospedaliero Cantonale, Bellinzona
Sponsor class: OTHER
Collaborators: name: Clinical Trial Unit Ente Ospedaliero Cantonale
First posted: 2019-10-30
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Proof of concept, double-blind, randomized, placebo-controlled trial with d-methadone proposed for the first time for use in the treatment of patients diagnosed with primary, moderate to very severe Restless Legs Syndrome (RLS). Its glutamatergic mechanism of action might be effective on RLS arousal pattern and sleep disturbance which highly impair the quality of life of RLS's patients.

Patients will take the study drug/placebo once a day for 30 consecutive days.


Eligibility criteria: Inclusion Criteria:

* Diagnosis of primary RLS.
* Moderate to very severe RLS defined as IRLS-RS score \> 10.
* Written informed consent.
* Willingness and ability to participate in the trial

Exclusion Criteria:

* Positive history of known causes of secondary RLS.
* Any other concomitant treatment for RLS (wash-out period: at least 7 days).
* Moderate-severe sleep apnea defined as Apnea Hypopnea Index ≥ 15.
* History or presence of clinically significant abnormality as assessed by neurological examination which in the opinion of the Investigator would jeopardize the safety of the patients or the validity of the study results.
* Evidence of clinically significant hepatic or renal impairment
* History or family history of sudden unexplained death or long QT syndrome.
* Any 12-lead ECG with demonstration of QTc ≥ 450 msec or a QRS interval ≥ 120 msec at Screening.
* Concomitant use of psycho-drugs dopamine agonists and opioids (wash-out period: at least 7 days).
* History or presence of any condition in which an opioid is contraindicated
* History of allergy or hypersensitivity to methadone or related drugs.
* Any clinically significant neurological, sleep, hepatic, renal, metabolic, hematological, immunological, cardiovascular, pulmonary, chronic pain, psychiatric or gastrointestinal disorder.
* Women who are pregnant or breast feeding.
* Inability to follow the procedures of the study, (e.g. due to language problems, psychological disorders, dementia, etc. of the participant).
* Previous enrolment into the current study.
* Enrolment of the investigator, his/her family members, employees and other dependent persons.
* Participation in another study with investigational drug within the 30 days preceding and during the present study.

Primary outcomes:
measure: Efficacy of d-methadone
timeFrame: 30 days
Secondary outcomes:
measure: Insomnia severity
timeFrame: 10 and 30 days
measure: Change in Quality of life
timeFrame: 10 and 30 days
measure: Periodic limb movements of sleep index
timeFrame: 10 days
measure: Actigrafic parameters
timeFrame: 10 and 30 days
Other outcomes:
Locations:
city: Milan
country: Italy
facility: Sleep Center, IRCCS San Raffaele
city: Bern
country: Switzerland
facility: Schlaf-Wach-Epilepsie Zentrum, Inselspital
city: Chur
country: Switzerland
facility: Neurologie / Schlaflabor Kantonsspital Graubünden
city: Lugano
country: Switzerland
facility: Sleep Center, Neurocenter of Southern Switzerland
Study officials:
affiliation: Ente Ospedaliero Cantonale, Neurocenter of Southern Switzerland
name: Mauro Manconi, Prof. MD
role: PRINCIPAL_INVESTIGATOR
References: