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A Proof of Concept, Phase 2, Double-blind, Randomized Trial With d-Methadone Product Versus Placebo (Glu-REST)

Primary Purpose

Restless Legs Syndrome

Status

Recruiting

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

D-methadone

Placebo

About this trial

This is an interventional treatment trial for Restless Legs Syndrome

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Sleep Center, IRCCS San Raffaele
Schlaf-Wach-Epilepsie Zentrum, Inselspital
Sleep Center, Neurocenter of Southern SwitzerlandRecruiting
Epilepsy and Sleep Center, University Hospital Zurich

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

25 mg d-methadone

Placebo

Arm Description

The experimental drug is a tablet formulation of d-methadone HCl in dose strength of 25 mg.

The placebo is an exact match to the active tablets in size, color and marking without the active ingredient d-methadone HCl.

Outcomes

Primary Outcome Measures

Efficacy of d-methadone

The percentage of responders to d-methadone treatment. A responder is defined as patient who has ≥ 50% reduction in the International RLS Rating Scale (IRLS-RS) score from baseline to end of the 30-day treatment period.

Secondary Outcome Measures

Insomnia severity

Change in insomnia severity from baseline to the end of 10-day dosing period and to end of the treatment period assessed by a using the Insomnia Severity Index (ISI)

Change in Quality of life

Change in quality of life from baseline to the end of 10-day dosing period and to end of the treatment period assessed assessed by a using the Restless Legs Syndrome Quality of Life Questionnaire (RLSQoL)

Periodic limb movements of sleep index

Change in Periodic limb movements of sleep (PLMS) index from baseline to end of 10-day dosing period measured by means of polysomnography recording

Actigrafic parameters

Change from baseline to the end of 10-day dosing period and to end of the treatment period on Total Sleep Time, Sleep Latency and Sleep Efficacy acquired assessed by actigraphy with measurements performed one week prior to the start of treatment, during the 10-day dosing period and one week at the end of the treatment.

Full Information

NCT ID

NCT04145674

First Posted

October 29, 2019

Last Updated

February 15, 2023

Sponsor

Mauro Manconi

Collaborators

Clinical Trial Unit Ente Ospedaliero Cantonale

1. Study Identification

Unique Protocol Identification Number

NCT04145674

Brief Title

A Proof of Concept, Phase 2, Double-blind, Randomized Trial With d-Methadone Product Versus Placebo

Acronym

Glu-REST

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

2. Study Status

Record Verification Date

February 2023

Overall Recruitment Status

Recruiting

Study Start Date

October 22, 2022 (Actual)

Primary Completion Date

July 30, 2024 (Anticipated)

Study Completion Date

July 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Mauro Manconi

Collaborators

Clinical Trial Unit Ente Ospedaliero Cantonale

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Restless Legs Syndrome

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

25 mg d-methadone

Arm Type

Experimental

Arm Description

The experimental drug is a tablet formulation of d-methadone HCl in dose strength of 25 mg.

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

The placebo is an exact match to the active tablets in size, color and marking without the active ingredient d-methadone HCl.

Intervention Type

Drug

Intervention Name(s)

D-methadone

Other Intervention Name(s)

esmethadone, dextromethadone, REL-1017

Intervention Description

Patients will take one tablet of 25 mg d-methadone once daily at 6 pm over a period of 30 days

Intervention Type

Other

Intervention Name(s)

Placebo

Intervention Description

Patients will take one tablet of placebo once daily at 6 pm over a period of 30 days

Primary Outcome Measure Information:

Title

Efficacy of d-methadone

Description

Time Frame

30 days

Secondary Outcome Measure Information:

Title

Insomnia severity

Description

Change in insomnia severity from baseline to the end of 10-day dosing period and to end of the treatment period assessed by a using the Insomnia Severity Index (ISI)

Time Frame

10 and 30 days

Title

Change in Quality of life

Description

Time Frame

10 and 30 days

Title

Periodic limb movements of sleep index

Description

Change in Periodic limb movements of sleep (PLMS) index from baseline to end of 10-day dosing period measured by means of polysomnography recording

Time Frame

10 days

Title

Actigrafic parameters

Description

Time Frame

10 and 30 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Mauro Manconi, Prof. MD

Phone

+41 91 811 68 25

mauro.manconi@eoc.ch

First Name & Middle Initial & Last Name or Official Title & Degree

Jane Frangi

Phone

+41 91 811 6050

JaneMarit.Frangi-Kultalahti@eoc.ch

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Mauro Manconi, Prof. MD

Organizational Affiliation

Ente Ospedaliero Cantonale, Neurocenter of Southern Switzerland

Official's Role

Principal Investigator

Facility Information:

Facility Name

Sleep Center, IRCCS San Raffaele

City

Milan

Country

Italy

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Luigi Ferini-Strambi, Prof. MD

ferinistrambi.luigi@hsr.it

First Name & Middle Initial & Last Name & Degree

Sara Marelli, MD

marelli.sara@hsr.it

First Name & Middle Initial & Last Name & Degree

Luigi Ferini-Strambi, Prof. MD

Facility Name

Schlaf-Wach-Epilepsie Zentrum, Inselspital

City

Bern

Country

Switzerland

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Markus Schmidt, MD

markus.schmidt@insel.ch

First Name & Middle Initial & Last Name & Degree

Markus Schmidt, MD

Facility Name

Sleep Center, Neurocenter of Southern Switzerland

City

Lugano

ZIP/Postal Code

6900

Country

Switzerland

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Mauro Manconi, Prof. MD

Phone

+41 91 811 68 25

mauro.manconi@eoc.ch

First Name & Middle Initial & Last Name & Degree

Jane frangi

Phone

+41 91 811 60 50

JaneMarit.Frangi-Kultalahti@eoc.ch

First Name & Middle Initial & Last Name & Degree

Mauro Manconi, Prof. MD

Facility Name

Epilepsy and Sleep Center, University Hospital Zurich

City

Zürich

ZIP/Postal Code

8091

Country

Switzerland

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Philipp Valko, MD

philipp.valko@usz.ch

First Name & Middle Initial & Last Name & Degree

Philipp Valko, MD

12. IPD Sharing Statement

Plan to Share IPD

Undecided

Learn more about this trial

A Proof of Concept, Phase 2, Double-blind, Randomized Trial With d-Methadone Product Versus Placebo

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