<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/NCT02967302</url>
  </required_header>
  <id_info>
    <org_study_id>NEUROIMPA2015</org_study_id>
    <nct_id>NCT02967302</nct_id>
  </id_info>
  <brief_title>NEUROIMPA - Intraarticular Application of Opioids in Chronic Arthritis of the Knee Joint</brief_title>
  <official_title>NEUROIMPA &quot;Intraarticular Application of Opioids in Chronic Arthritis&quot;</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hildrun Haibel</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>DLR German Aerospace Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Charite University, Berlin, Germany</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      To investigate pain and inflammatory parameters (cytokines, immune cells) in knee joint&#xD;
      tissue of chronic arthritis patients following intraarticular (i.a.) injections of morphine,&#xD;
      a standard steroid or placebo.&#xD;
&#xD;
      The primary hypothesis is that i.a. morphine results in significantly lower pain scores and&#xD;
      supplemental analgesic consumption than placebo during the first week after injection, an&#xD;
      efficacy comparable to standard i.a. steroid (triamcinolone) medication.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      3 arm, double blind, placebo controlled, prospective, mo-nocenter study, which will be&#xD;
      conducted in the Department of Rheumatology, Charité University Medicine Berlin, Cam-pus&#xD;
      Benjamin Franklin in collaboration with several rheu-matology and orthopedic practices in the&#xD;
      Berlin area. Ultra-sound guided synovial needle biopsy and interventions will only be&#xD;
      performed at CBF.&#xD;
&#xD;
      Eligible patients will be treated with either morphine 3 mg i.a., NaCl 0.9% i.a. or&#xD;
      triamcinolone 40 mg i.a. at Baseline. The entire study period will be 2 weeks per patient.&#xD;
&#xD;
      Assessment of the primary outcome parameter will be at week 1. The patients will be monitored&#xD;
      closely throughout the entire study period with a total of 4 visits (screening, baseline,&#xD;
      week 1, week 2).&#xD;
&#xD;
      Safety data will be collected in the adverse events form, vital parameters, physical&#xD;
      examination and laboratory tests dur-ing the whole study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">August 2015</start_date>
  <completion_date type="Anticipated">December 2021</completion_date>
  <primary_completion_date type="Anticipated">December 2021</primary_completion_date>
  <phase>Phase 2/Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Reduction of pain intensity (on a 100mm VAS) at 8 a.m. on day 7 compared to baseline</measure>
    <time_frame>1 week</time_frame>
    <description>Reduction of pain intensity (on a 100mm VAS) at 8 a.m. on day 7 compared to baseline</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Area under the VAS curve (AUC) of VAS pain during the first week until 8 p.m. on day 7</measure>
    <time_frame>1 week</time_frame>
    <description>Area under the VAS curve (AUC) of VAS pain during the first week until 8 p.m. on day 7</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pain intensity on McGill pain questionnaire (MPQ) at baseline, week 1 and 2</measure>
    <time_frame>2 weeks</time_frame>
    <description>Pain intensity on McGill pain questionnaire (MPQ) at baseline, week 1 and 2</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>daily activities at baseline, week 1 and 2</measure>
    <time_frame>2 weeks</time_frame>
    <description>daily activities at baseline, week 1 and 2</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>activity and mobility of the knee joint (Lysholm Gilquist-Score) at baseline, week 1 and 2</measure>
    <time_frame>2 weeks</time_frame>
    <description>activity and mobility of the knee joint (Lysholm Gilquist-Score) at baseline, week 1 and 2</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>WOMAC scale (before i.a. injections at baseline, week 1 and 2)</measure>
    <time_frame>2 weeks</time_frame>
    <description>WOMAC scale (before i.a. injections and at the end of each week)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>nflammatory parameters (cellular infiltrate, opioid receptors and peptides, IL-17, TNFα) in synovial biopsies and fluid (before i.a. medication at baseline and week 1),</measure>
    <time_frame>1 weeks</time_frame>
    <description>nflammatory parameters (cellular infiltrate, opioid receptors and peptides, IL-17, TNFα) in synovial biopsies and fluid (before and 7 days af-ter i.a. medication),</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>supplementary analgesic consumption continuously in the patients diary, recorded at week 1 and 2</measure>
    <time_frame>2 weeks</time_frame>
    <description>supplementary analgesic consumption continuously in the patients diary, recorded at week 1 and 2</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Any systemic (e.g. nausea, sedation) and local side effects (infection, tissue injury) will be recorded continuously in the patients diary, recorded at week 1 and week 2.</measure>
    <time_frame>Screening, Baseline, week 1, week 2</time_frame>
    <description>Any systemic (e.g. nausea, sedation) and local side effects (infection, tissue injury) will be recorded continuously in the patients diary, recorded at week 1 and 2.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">112</enrollment>
  <condition>Knee Arthritis</condition>
  <arm_group>
    <arm_group_label>Morphine Sulfate</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Morphine 3 mg intraarticular once at baseline</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Triamcinolone</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Triamcinolone 40 mg intraarticular once at baseline</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>NaCl 0,9% 5 ml intraarticular at baseline</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Morphine Sulfate</intervention_name>
    <description>active intervention</description>
    <arm_group_label>Morphine Sulfate</arm_group_label>
    <other_name>Morphin Hexal</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Triamcinolone</intervention_name>
    <description>active control</description>
    <arm_group_label>Triamcinolone</arm_group_label>
    <other_name>Triamcinolon Liechtenstein</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>placebo</intervention_name>
    <description>placebo control</description>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>NaCl 0.9%</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Clinically detectable and/or ultrasound-visible knee ef-fusion as part of&#xD;
             spondyloarthritis (Assessments in SpondyloArthritis international Society, ASAS&#xD;
             criteria), Rheumatoid Arthritis, RA (according to American Col-lege of Rheumatology,&#xD;
             ACR criteria), undifferentiated mono- or oligoarthritis, Osteoarthritis of the knee,&#xD;
             OA.&#xD;
&#xD;
          2. baseline pain score (on a 100 mm Visual Analogue Scale, VAS) &gt;40 mm;&#xD;
&#xD;
          3. male and female patients, age ≥18 - 80 years,&#xD;
&#xD;
          4. body weight 50 - 90 kg.&#xD;
&#xD;
          5. Able and willing to give a written informed consent and comply with the requirements&#xD;
             of the study protocol. Only patients who give written informed consent will be&#xD;
             in-cluded in the trial.&#xD;
&#xD;
          6. If female: either not of child-bearing potential (meno-pausal since 1 year or&#xD;
             surgically sterile) or is willing and able to practice a reliable method of&#xD;
             contraception throughout the study with a pearl index &lt;1. Reliable methods of&#xD;
             contraception are: condoms plus other methods: implants, injecatbles, combined oral&#xD;
             contracep-tives, intrauterine devices, initiated at least 90 days prior to screening.&#xD;
             Further reliable methods are a vasecto-mised partner (at least 1 year prior to&#xD;
             enrolment), sexual-ly abstinent, surgically sterilized (including hysterecto-my),&#xD;
             postmenopausal defined as at least 1 year of spon-taneous amenorrhea (in questionable&#xD;
             cases a blood sample with simultaneous levels of follicle stimulating hormone (FSH)&#xD;
             above 40 U/l and estradiol below 30 nl/l is confirmatory).&#xD;
&#xD;
          7. If male: either not of child-bearing potential (surgically sterilized, e.g. vasectomy)&#xD;
             or is willing and able to prac-tice a reliable method of contraception with a pearl&#xD;
             index &lt;1 (see inclusion criterium 6) throughout the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Severe cardiovascular, respiratory, metabolic, neurologi-cal, psychiatric disorders;&#xD;
             current bacterial infection es-pecially of the knee&#xD;
&#xD;
          2. abuse of analgesics, benzodiazepines, alcohol; &quot;hard drugs&quot;&#xD;
&#xD;
          3. pregnancy, lactation&#xD;
&#xD;
          4. before biopsy thrombocyte count &lt; 100/nl, Quick &lt;50%&#xD;
&#xD;
          5. intake of anticoagulants, anti-aggregants as monothera-py such as ASS 100 will be&#xD;
             allowed&#xD;
&#xD;
          6. participation in an investigational trial during the last 30 days or 5 HLT whichever&#xD;
             is longer&#xD;
&#xD;
          7. treatment with intraarticular steroids during the past 4 weeks in the selected joint.&#xD;
&#xD;
          8. Patients with a history of a severe psychiatric illness, which might interfere with&#xD;
             the patient's ability to under-stand the requirements of the study and assessment.&#xD;
&#xD;
          9. Patients who are institutionalised due to regulatory or juridical order. Patients who&#xD;
             are an employee of the in-vestigator or study site, with direct involvement in the&#xD;
             proposed study or other studies under the direction of that investigator or study&#xD;
             site, as well as family members of the employees or the investigator.&#xD;
&#xD;
         10. Known hypersensitivity to any component of the study medication to morphine or&#xD;
             triamcinolone, ileus, respira-tory depression, severe chronic obstructive airway&#xD;
             dis-eases, acute abdomen, coagulopathy and/ or infections of the injection site,&#xD;
             instability of the injected joint, psori-atic skin manifestation at the injection&#xD;
             site, periarticular calcification, non-vascularized bone necrosis, tendon rupture,&#xD;
             Charcot-joint.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Hildrun Haibel, PD Dr</last_name>
    <role>Principal Investigator</role>
    <affiliation>Charité CBF, Rheumatology, Berlin, Germany</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Charité CBF Rheumatology</name>
      <address>
        <city>Berlin</city>
        <zip>12203</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>August 2021</verification_date>
  <study_first_submitted>November 10, 2016</study_first_submitted>
  <study_first_submitted_qc>November 15, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 18, 2016</study_first_posted>
  <last_update_submitted>August 2, 2021</last_update_submitted>
  <last_update_submitted_qc>August 2, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">August 3, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Charite University, Berlin, Germany</investigator_affiliation>
    <investigator_full_name>Hildrun Haibel</investigator_full_name>
    <investigator_title>Priv. Doz. Dr. med. Hildrun Haibel</investigator_title>
  </responsible_party>
  <keyword>knee arthritis, morphine, local injection, pain</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Arthritis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Triamcinolone</mesh_term>
    <mesh_term>Morphine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>no plan</ipd_description>
  </patient_data>
  <!-- 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/NCT02967302
org study id: NEUROIMPA2015
nct id: NCT02967302
lead sponsor: 
collaborator: 
has dmc: Yes
To investigate pain and inflammatory parameters (cytokines, immune cells) in knee joint
      tissue of chronic arthritis patients following intraarticular (i.a.) injections of morphine,
      a standard steroid or placebo.

      The primary hypothesis is that i.a. morphine results in significantly lower pain scores and
      supplemental analgesic consumption than placebo during the first week after injection, an
      efficacy comparable to standard i.a. steroid (triamcinolone) medication.
3 arm, double blind, placebo controlled, prospective, mo-nocenter study, which will be
      conducted in the Department of Rheumatology, Charité University Medicine Berlin, Cam-pus
      Benjamin Franklin in collaboration with several rheu-matology and orthopedic practices in the
      Berlin area. Ultra-sound guided synovial needle biopsy and interventions will only be
      performed at CBF.

      Eligible patients will be treated with either morphine 3 mg i.a., NaCl 0.9% i.a. or
      triamcinolone 40 mg i.a. at Baseline. The entire study period will be 2 weeks per patient.

      Assessment of the primary outcome parameter will be at week 1. The patients will be monitored
      closely throughout the entire study period with a total of 4 visits (screening, baseline,
      week 1, week 2).

      Safety data will be collected in the adverse events form, vital parameters, physical
      examination and laboratory tests dur-ing the whole study.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Reduction of pain intensity (on a 100mm VAS) at 8 a.m. on day 7 compared to baseline
time frame: 1 week
description: Reduction of pain intensity (on a 100mm VAS) at 8 a.m. on day 7 compared to baseline
measure: Area under the VAS curve (AUC) of VAS pain during the first week until 8 p.m. on day 7
time frame: 1 week
description: Area under the VAS curve (AUC) of VAS pain during the first week until 8 p.m. on day 7
measure: Pain intensity on McGill pain questionnaire (MPQ) at baseline, week 1 and 2
time frame: 2 weeks
description: Pain intensity on McGill pain questionnaire (MPQ) at baseline, week 1 and 2
measure: daily activities at baseline, week 1 and 2
time frame: 2 weeks
description: daily activities at baseline, week 1 and 2
measure: activity and mobility of the knee joint (Lysholm Gilquist-Score) at baseline, week 1 and 2
time frame: 2 weeks
description: activity and mobility of the knee joint (Lysholm Gilquist-Score) at baseline, week 1 and 2
measure: WOMAC scale (before i.a. injections at baseline, week 1 and 2)
time frame: 2 weeks
description: WOMAC scale (before i.a. injections and at the end of each week)
measure: nflammatory parameters (cellular infiltrate, opioid receptors and peptides, IL-17, TNFα) in synovial biopsies and fluid (before i.a. medication at baseline and week 1),
time frame: 1 weeks
description: nflammatory parameters (cellular infiltrate, opioid receptors and peptides, IL-17, TNFα) in synovial biopsies and fluid (before and 7 days af-ter i.a. medication),
measure: supplementary analgesic consumption continuously in the patients diary, recorded at week 1 and 2
time frame: 2 weeks
description: supplementary analgesic consumption continuously in the patients diary, recorded at week 1 and 2
measure: Any systemic (e.g. nausea, sedation) and local side effects (infection, tissue injury) will be recorded continuously in the patients diary, recorded at week 1 and week 2.
time frame: Screening, Baseline, week 1, week 2
description: Any systemic (e.g. nausea, sedation) and local side effects (infection, tissue injury) will be recorded continuously in the patients diary, recorded at week 1 and 2.
arm group label: Morphine Sulfate
arm group type: Experimental
description: Morphine 3 mg intraarticular once at baseline
arm group label: Triamcinolone
arm group type: Active Comparator
description: Triamcinolone 40 mg intraarticular once at baseline
arm group label: Placebo
arm group type: Placebo Comparator
description: NaCl 0,9% 5 ml intraarticular at baseline
intervention type: Drug
intervention name: Morphine Sulfate
description: active intervention
arm group label: Morphine Sulfate
other name: Morphin Hexal
intervention type: Drug
intervention name: Triamcinolone
description: active control
arm group label: Triamcinolone
other name: Triamcinolon Liechtenstein
intervention type: Drug
intervention name: placebo
description: placebo control
arm group label: Placebo
other name: NaCl 0.9%
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Hildrun Haibel, PD Dr
role: Principal Investigator
affiliation: Charité CBF, Rheumatology, Berlin, Germany
facility: 
country: Germany
responsible party type: Sponsor-Investigator
investigator affiliation: Charite University, Berlin, Germany
investigator full name: Hildrun Haibel
investigator title: Priv. Doz. Dr. med. Hildrun Haibel
mesh term: Arthritis
mesh term: Triamcinolone
mesh term: Morphine
sharing ipd: No
ipd description: no plan