Effectiveness and Safety of Methadone Versus Placebo for the Control of Neuropathic Pain in Different Etiologies

NCT05235191 | Completed Phase 3 DMC

• 1 other identifier: 45397515.2.0000.0068
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

Opioids are currently ranked as third-line agents for neuropathic pain (NP) treatment. The opioids more frequently tested for NP were tramadol, oxycodone and morphine. In the present study test the safety and effectiveness of methadone in patients with NP who remain symptomatic despite the use of first and second line drugs in a placebo-controlled randomized approach.

Conditions

Neuropathic Pain

Keywords

Methadone; Neuropathic Pain; Opioid; Pain

Outcome Measures

Primary Outcomes (3)

• Pain intensity change from baseline, assessed by the visual analogue scale (VAS)

  To evaluate the analgesic effect of methadone (number of patients with ≥ 30% pain intensity change from baseline) compared to placebo in patients with neuropathic pain (NP) of different etiologies. The impact on the average change in the intensity of NP (baseline) will be evaluated, with the main objective being a higher number of responders in the methadone at study completion compared to the placebo group. Responder is defined as pain intensity reduction greater than or equal to 30% compared to the baseline intensity of NP. It will be measured according to a visual analogue scale (VAS), 100 mm long, anchored by two verbal descriptors (0 mm being the total absence of pain and 100 mm being the worst imaginable pain). The measurement of the average change in the intensity of NP (baseline) will be performed by comparing the value on the first visit (day 0) with the value on the final visit (day 56).

  0 and 56 days

• Incidence of Serious Treatment-Emergent Adverse Events assessed by a questionnaire

  The Incidence of Serious Treatment-Emergent Adverse Events will be assessed by measuring the number of participants who experience Serious Adverse Events with the use of methadone or placebo. The search for the adverse events will be done with a questionnaire containing the main adverse events previously described in the medical literature and in the manufacturer's label (methadone). In addition, unexpected adverse events will also be described in detail and reported to the responsible institution. The definition of a serious treatment adverse event will be made in accordance with the rules of the National System of Notifications for Health Surveillance-NOTIVISA. Each serious adverse event will be described in detail and notified to the responsible institution.The comparison between the incidence of Serious Treatment-Emergent Adverse Events will be made between the groups (methadone and placebo) at the end of the study.

  56 days

• Incidence of methadone addiction/misuse or withdrawal syndrome assessed by a prespecified questionnaire

  The incidence of methadone addiction/misuse or withdrawal syndrome will be assessed by a prespecified questionnaire, containing eight clinical characteristics that may be related to the methadone addition/misuse or withdrawal syndromes. If one or more of those 8 characteristics listed in the questionnaire are present, an immediate communication will be made to the assistant physician (for diagnostic confirmation and referral to multidisciplinary treatment), as well as the exclusion of the individual from the study (after discussion with the research coordinators).

  56 days

Secondary Outcomes (1)

• Incidence of drop-outs due to Non-Serious Treatment-Emergent Adverse Events assessed by a questionnaire

  56 days

Other Outcomes (3)

• Improvement in sleep quality, assessed by The Medical Outcomes Study Sleep Problem Index II (SPI II)

  56 days

• Improvement in mood and anxiety symptoms, assessed by The Hospital Anxiety and Depression Scale (HADS)

  56 days

• Improvement in quality of life, assessed by The Short-Form 6 dimensions Questionnaire (SF-6D)

  56 days

Study Arms (2)

methadone

EXPERIMENTAL

In this arm patients will take methadone 5mg

Drug: methadone tablets

placebo

PLACEBO COMPARATOR

In this arm patients will take placebo tablets (the same number, color and physical aspects as the methadone tablets).

Drug: Placebo

Interventions

methadone tablets DRUG

The intervention with the active drug (methadone) will start with the dose of 1 tablet (5 mg) twice a day (every 12 hours) and titrated on subsequent visits up to the maximum dose of 6 tablets a day (totaling 30 mg divided into 2 daily doses to facilitate therapeutic adherence).

Also known as: Mytedom

methadone

Placebo DRUG

In this arm patients will take placebo tablets (the same number, color and physical aspects as the methadone tablets).

placebo

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Presence of an exclusive neuropathic pain (without other main pain syndrome occurring concomitantly at the same body area);
• Pain lasting at least 6 months (chronic) and being present most of the days;
• Pain fulfilling the current IASP (The International Association for the Study of Pain) criteria for defined Neuropathic Pain and with a score on the DN4 questionnaire (Douleur Neuropathique Pain 4 Questions) ≥ 4 (positive);
• The pain must be of at least moderate intensity (score on a visual analogue pain scale ≥ 40/100) despite the use of first and second line drugs in an adequate dosing.

You may not qualify if:

• Patients under the age of 18 or over 85;
• Who has neuropathic pain duration less than 6 months;
• Who do not have an exclusive neuropathic pain (without other main pain syndrome occurring concomitantly at the same body area);
• Patients with neuropathic pain intensity less than 40 out of 100 on a visual analogue pain scale;
• Who scored less than 4 on the DN4 scale;
• Who wishes at any time to abandon the study;
• Patients with a previous allergic reaction to any of the drugs involved in the study (methadone) or placebo components;
• Patients in current use or in the last 14 days of medication (s) inhibitor (s) of monoamine oxidase (MAOI) or other medications with potential drug interaction with methadone;
• Patients in current continuous use of opioids (including methadone);
• Patients with a history of opioid abuse;
• Patients with a history of heavy/abusive alcohol consumption;
• Who is under judicial litigation, police custody or institutionalized for other reasons;
• Pregnant women, lactating women or women of childbearing age (without the use of an adequate contraceptive method);
• Who uses illegal drugs;
• Patients unable to assess the risks and benefits of participating in the present study (eg, language barriers, psychiatric disorders or cognitive impairment);

Sponsors & Collaborators

• University of Sao Paulo: lead

Study Sites (1)

University of São Paulo

São Paulo, 05403-000, Brazil

Location

Related Publications (1)

• Pentiado Junior JAM, Barbosa MM, Kubota GT, Martins PN, Moreira LI, Fernandes AM, da Silva VA, Junior JR, Yeng LT, Teixeira MJ, Ciampi de Andrade D. METHA-NeP: effectiveness and safety of methadone for neuropathic pain: a controlled randomized trial. Pain. 2025 Mar 1;166(3):557-570. doi: 10.1097/j.pain.0000000000003413. Epub 2024 Oct 22.

  PMID: 39432734 DERIVED

MeSH Terms

Conditions

Neuralgia; Pain

Interventions

Methadone

Condition Hierarchy (Ancestors)

Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Ketones; Organic Chemicals

Study Officials

• Daniel C. de Andrade, PhD

  University of Sao Paulo

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: June 18, 2020
• First Posted: February 11, 2022
• Study Start: September 6, 2019
• Primary Completion: January 20, 2023
• Study Completion: January 20, 2023
• Last Updated: February 8, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: The IPD will be available after the estimated study completion time (August/2021) and for five years.
• Access Criteria: The complete IPD will be sent by e-mail after other researchers request it for use in individual patient data (IPD) meta-analysis. Other specific situations will be discussed on a case-by-case basis.

Locations

BR (1)