<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02233452</url>
  </required_header>
  <id_info>
    <org_study_id>Methadone plus ketamine</org_study_id>
    <nct_id>NCT02233452</nct_id>
  </id_info>
  <brief_title>Methadone and Ketamine for Neuropathic Pain Treatment</brief_title>
  <official_title>Management of Neuropathic Chronic Pain With Methadone Combined With Ketamine: Randomized, Double Blind, Active-controlled Clinical Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Universidade Federal de Santa Maria</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Santa Casa de Misericórdia de Belo Horizonte</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Hospital de Clinicas de Porto Alegre</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Universidade Federal de Santa Maria</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Methadone and ketamine are effective for neuropathic pain management. However, the benefits&#xD;
      of the association of both drugs are uncertain. Here, the investigators conducted a&#xD;
      randomized, double-blind, in parallel, active controlled clinical trial to test the&#xD;
      hypothesis that methadone combined ketamine (methadone/ketamine) is more effective than&#xD;
      methadone or ketamine alone in reducing neuropathic pain.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Either oral methadone or ketamine have been used in neuropathic pain management, however, the&#xD;
      benefits of the association of both drugs are uncertain. Here, we conducted a randomized,&#xD;
      double-blind, in parallel, active controlled clinical trial to test the hypothesis that&#xD;
      methadone combined ketamine (methadone/ketamine) is more effective than methadone or ketamine&#xD;
      alone in reducing neuropathic pain.&#xD;
&#xD;
      Methods: Fourthly two patients with neuropathic pain refractory to conventional therapy were&#xD;
      randomly assigned to receive during three months oral methadone (n= 13), ketamine (n=13) or&#xD;
      methadone combined with ketamine (n=13). The primary outcome was pain score on visual&#xD;
      analogical scale (VAS) assessed on baseline, 8, 15, 30, 60 and 90 days throughout the&#xD;
      treatment, and the secondary outcomes were symptoms of neuropathic pain such as allodynia,&#xD;
      burning or shooting pain as well the side effects.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>January 2012</start_date>
  <completion_date type="Actual">August 2012</completion_date>
  <primary_completion_date type="Actual">August 2012</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Factorial Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The primary outcome was pain intensity as assessed by visual analogical scale (VAS) scores</measure>
    <time_frame>90 days</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>The secondary outcomes were the presence of burning and/or shooting pain, allodynia and side effects.</measure>
    <time_frame>90 days</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">37</enrollment>
  <condition>Neuropathic Pain</condition>
  <arm_group>
    <arm_group_label>Methadone</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Group treated with methadone solution.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Ketamine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Group treated with ketamine solution</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Methadone plus ketamine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Group treated with methadone plus ketamine solution</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Methadone</intervention_name>
    <description>The solution of methadone was prepared by mixing 10 ml of methadone (10 mg/ml) and 90 ml of saline 0.9% (Baxter, São Paulo, Brazil)</description>
    <arm_group_label>Methadone</arm_group_label>
    <other_name>Methadone hydrochloride, Cristália® (São Paulo, Brazil)</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ketamine</intervention_name>
    <description>The solution of ketamine was prepared by mixing 20 ml of S(+)-ketamine hydrochloride (50 mg/ml, Cristália®, São Paulo, Brazil) and 80 ml of saline 0.9% (Baxter, São Paulo, Brazil), obtaining a concentration of 10 mg/ml of ketamine.</description>
    <arm_group_label>Ketamine</arm_group_label>
    <other_name>S(+)-ketamine hydrochloride, Cristália®, São Paulo, Brazil</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Methadone plus Ketamine</intervention_name>
    <description>the solution of methadone, ketamine was prepared by mixing 10 ml of methadone hydrochloride (10 mg/ml, Cristália®, São Paulo, Brazil), 20 ml of S(+)-ketamine hydrochloride (50 mg/ml, Cristália®, São Paulo, Brazil) and 70 ml of saline 0.9% (Baxter, São Paulo, Brazil), obtaining a concentration of 1 mg/ml of methadone and 10 mg/ml of ketamine.</description>
    <arm_group_label>Methadone plus ketamine</arm_group_label>
    <other_name>methadone and S(+)-ketamine, Cristália®, São Paulo, Brazil</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  patients complaining of pain for more than 6 months with neuropathic pain poorly&#xD;
             responsive to drugs used to treat neuropathic pain (i.e. opioid, non-opioid,&#xD;
             anticonvulsants, antidepressants), who were 22 to 77 years old&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  patients with a history of severe psychiatric disorder,&#xD;
&#xD;
          -  misuse of illegal drugs or&#xD;
&#xD;
          -  hepatic disease&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>22 Years</minimum_age>
    <maximum_age>77 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Juliano Ferreira, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Federal University of Santa Catarina</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University Hospital in Santa Maria</name>
      <address>
        <city>Santa Maria</city>
        <state>Rio Grande do Sul</state>
        <zip>97105-900</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <verification_date>September 2014</verification_date>
  <study_first_submitted>August 22, 2014</study_first_submitted>
  <study_first_submitted_qc>September 5, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 8, 2014</study_first_posted>
  <last_update_submitted>September 5, 2014</last_update_submitted>
  <last_update_submitted_qc>September 5, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 8, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Universidade Federal de Santa Maria</investigator_affiliation>
    <investigator_full_name>Juliano Ferreira</investigator_full_name>
    <investigator_title>PhD</investigator_title>
  </responsible_party>
  <keyword>Neuropathic pain</keyword>
  <keyword>Methadone</keyword>
  <keyword>Ketamine</keyword>
  <keyword>Multimodal analgesia</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neuralgia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ketamine</mesh_term>
    <mesh_term>Methadone</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02233452
org study id: Methadone plus ketamine
nct id: NCT02233452
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
Methadone and ketamine are effective for neuropathic pain management. However, the benefits
      of the association of both drugs are uncertain. Here, the investigators conducted a
      randomized, double-blind, in parallel, active controlled clinical trial to test the
      hypothesis that methadone combined ketamine (methadone/ketamine) is more effective than
      methadone or ketamine alone in reducing neuropathic pain.
Either oral methadone or ketamine have been used in neuropathic pain management, however, the
      benefits of the association of both drugs are uncertain. Here, we conducted a randomized,
      double-blind, in parallel, active controlled clinical trial to test the hypothesis that
      methadone combined ketamine (methadone/ketamine) is more effective than methadone or ketamine
      alone in reducing neuropathic pain.

      Methods: Fourthly two patients with neuropathic pain refractory to conventional therapy were
      randomly assigned to receive during three months oral methadone (n= 13), ketamine (n=13) or
      methadone combined with ketamine (n=13). The primary outcome was pain score on visual
      analogical scale (VAS) assessed on baseline, 8, 15, 30, 60 and 90 days throughout the
      treatment, and the secondary outcomes were symptoms of neuropathic pain such as allodynia,
      burning or shooting pain as well the side effects.
allocation: Randomized
intervention model: Factorial Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: The primary outcome was pain intensity as assessed by visual analogical scale (VAS) scores
time frame: 90 days
measure: The secondary outcomes were the presence of burning and/or shooting pain, allodynia and side effects.
time frame: 90 days
arm group label: Methadone
arm group type: Active Comparator
description: Group treated with methadone solution.
arm group label: Ketamine
arm group type: Active Comparator
description: Group treated with ketamine solution
arm group label: Methadone plus ketamine
arm group type: Active Comparator
description: Group treated with methadone plus ketamine solution
intervention type: Drug
intervention name: Methadone
description: The solution of methadone was prepared by mixing 10 ml of methadone (10 mg/ml) and 90 ml of saline 0.9% (Baxter, São Paulo, Brazil)
arm group label: Methadone
other name: Methadone hydrochloride, Cristália® (São Paulo, Brazil)
intervention type: Drug
intervention name: Ketamine
description: The solution of ketamine was prepared by mixing 20 ml of S(+)-ketamine hydrochloride (50 mg/ml, Cristália®, São Paulo, Brazil) and 80 ml of saline 0.9% (Baxter, São Paulo, Brazil), obtaining a concentration of 10 mg/ml of ketamine.
arm group label: Ketamine
other name: S(+)-ketamine hydrochloride, Cristália®, São Paulo, Brazil
intervention type: Drug
intervention name: Methadone plus Ketamine
description: the solution of methadone, ketamine was prepared by mixing 10 ml of methadone hydrochloride (10 mg/ml, Cristália®, São Paulo, Brazil), 20 ml of S(+)-ketamine hydrochloride (50 mg/ml, Cristália®, São Paulo, Brazil) and 70 ml of saline 0.9% (Baxter, São Paulo, Brazil), obtaining a concentration of 1 mg/ml of methadone and 10 mg/ml of ketamine.
arm group label: Methadone plus ketamine
other name: methadone and S(+)-ketamine, Cristália®, São Paulo, Brazil
criteria: 
gender: All
minimum age: 22 Years
maximum age: 77 Years
healthy volunteers: No
last name: Juliano Ferreira, PhD
role: Principal Investigator
affiliation: Federal University of Santa Catarina
facility: 
country: Brazil
responsible party type: Principal Investigator
investigator affiliation: Universidade Federal de Santa Maria
investigator full name: Juliano Ferreira
investigator title: PhD
mesh term: Neuralgia
mesh term: Ketamine
mesh term: Methadone