<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/NCT02967640</url>
  </required_header>
  <id_info>
    <org_study_id>2012/1199</org_study_id>
    <secondary_id>2012-002782-35</secondary_id>
    <nct_id>NCT02967640</nct_id>
  </id_info>
  <brief_title>Does Subacromial Injection With Glutamate Receptor Antagonist, Ketamine, Attenuate Pain in Rotator Cuff Tendinopathy?</brief_title>
  <official_title>Does Subacromial Injection With Glutamate Receptor (NMDAR) Antagonist, Ketamine, Attenuate Pain in Rotator Cuff Tendinopathy?</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Helse Møre og Romsdal HF</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Helse Møre og Romsdal HF</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The hypothesis of the present study is that in patients with rotator cuff tendinopathy a&#xD;
      specific pharmacological blocking of peripheral glutamate-receptor N-methyl-d-aspartate&#xD;
      receptor type1 (NMDAR) glutamate receptors will result in pain alleviation. Activated NMDAR1&#xD;
      has been demonstrated to be crucial for pain regulation in various pain disorders, and in&#xD;
      biopsies from patients with tendinopathy, NMDAR1 was found to be activated.&#xD;
&#xD;
      To test this hypothesis a specific NMDA receptor antagonist, ketalar (ketamine), will be&#xD;
      injected guided by ultrasound into the subacromial space in patients with rotator cuff&#xD;
      tendinopathy, and subsequently the pain response will be assessed.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">May 1, 2018</start_date>
  <completion_date type="Anticipated">December 2023</completion_date>
  <primary_completion_date type="Anticipated">December 2023</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>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Supraspinatus pressure pain threshold</measure>
    <time_frame>30 minutes</time_frame>
    <description>Comparison of supraspinatus pressure pain threshold measured in Lbs/cm3, after selective N-methyl-d-aspartate receptor type 1 blocking by ketalar injection subacromially controlled against ringer acetate injection</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Western Ontario Rotator Cuff Index</measure>
    <time_frame>30 minutes</time_frame>
    <description>Comparisons of shoulder function assessed by Western Ontario Rotator Cuff index in the same patient group after selective N-methyl-d-aspartate receptor type 1 blocking by ketalar injection subacromially controlled against Ringer acetate injection.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Oxford Shoulder Score</measure>
    <time_frame>30 minutes</time_frame>
    <description>Comparison of shoulder function assessed by Oxford Shoulder Score after selective N-methyl-d-aspartate receptor type 1 blocking by ketalar injection subacromially controlled against Ringer acetate injection.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pain</measure>
    <time_frame>30 minutes</time_frame>
    <description>Comparison of pain assessed by a visual analogue scale both at rest and abduction, after selective N-methyl-d-aspartate receptor type 1 blocking by ketalar injection subacromially controlled against Ringer acetate injection.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pressure pain tolerance</measure>
    <time_frame>30 minutes</time_frame>
    <description>Comparison of pressure pain tolerance measured in Lbs/cm3, both at rest and abduction, after selective N-methyl-d-aspartate receptor type 1 blocking by ketalar injection subacromially controlled against Ringer acetate injection.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Rotator Cuff Tendinitis</condition>
  <condition>Chronic Pain</condition>
  <arm_group>
    <arm_group_label>Ketalar</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>ketalar injection, subacromial</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>physiological sodium chloride (NaCl 9%) injection, subacromial</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ketalar</intervention_name>
    <description>2,5 ml - if well tolerated immediately followed by another 2,5 ml - of an approximately 1 mg/ml ketalar solution (1 ml of ketalar 10 mg/ml + 9 ml of NaCl 9%) injected 2 times with 1-12 weeks between each injection</description>
    <arm_group_label>Ketalar</arm_group_label>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>Ketamine</other_name>
    <other_name>Ketanest</other_name>
    <other_name>Ketaset</other_name>
    <other_name>Calipsol</other_name>
    <other_name>Kalipsol</other_name>
    <other_name>Calypsol</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>NaCl 9%</intervention_name>
    <description>2,5 ml - if well tolerated immediately followed by another 2,5 ml - of a 9% NaCl solution injected 2 times with 1-12 weeks between each injection</description>
    <arm_group_label>Ketalar</arm_group_label>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  diagnosis of rotator cuff tendinopathy by exercise-related shoulder pain with positive&#xD;
             impingement tests as described by Hawkins and Neers, and MRI findings consistent with&#xD;
             tendinopathy.&#xD;
&#xD;
          -  Symptom duration at least 1 year to ensure neuronal ingrowth and NMDAR expression&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  previous surgery in any shoulder.&#xD;
&#xD;
          -  previous cortisone use, either as injections or orally&#xD;
&#xD;
          -  symptoms or signs of cervicobrachialgia or polyneuropathy&#xD;
&#xD;
          -  full thickness rotator cuff ruptures verified by MRI&#xD;
&#xD;
          -  primary inflammatory mediated pain, hence, patients with glenohumeral arthrosis,&#xD;
             glenohumeral arthritis or systemic disorders predisposing for arthritis&#xD;
&#xD;
          -  a central component of pain perception manifested by radiating pain in the involved&#xD;
             limb; implying worse outcome after subacromial decompression.&#xD;
&#xD;
          -  pregnancy&#xD;
&#xD;
          -  breastfeeding&#xD;
&#xD;
          -  reduced liver function (Increased serum bilirubin, ASAT or ALAT), decompensated heart&#xD;
             failure (NYHA class 3-4)&#xD;
&#xD;
          -  increased intracranial pressure or disease of the central nervous system (CNS)&#xD;
&#xD;
          -  chronic alcoholism&#xD;
&#xD;
          -  epilepsy&#xD;
&#xD;
          -  psychiatric disease, increased intraocular pressure&#xD;
&#xD;
          -  acute intermittent porphyria&#xD;
&#xD;
          -  hyperthyroidism&#xD;
&#xD;
          -  use of thyroid hormones&#xD;
&#xD;
          -  upper respiratory tract infections&#xD;
&#xD;
          -  pneumonia&#xD;
&#xD;
          -  intracranial lesions&#xD;
&#xD;
          -  acute head injuries&#xD;
&#xD;
          -  ocular injuries&#xD;
&#xD;
          -  hydrocephalus&#xD;
&#xD;
          -  risk factors predisposing for intra-articular bleeding&#xD;
&#xD;
          -  increased risk of infection&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Oystein B Lian, md phd</last_name>
    <role>Study Chair</role>
    <affiliation>Helse Nord-Trøndelag HF</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Ola M Lian, md</last_name>
    <phone>+47 272847</phone>
    <email>Ola.Midtsether.Lian@helse-mr.no</email>
  </overall_contact>
  <location>
    <facility>
      <name>Department of Orthopedic Surgery, Kristiansund Hospital</name>
      <address>
        <city>Kristiansund</city>
        <country>Norway</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ola M Lian, MD</last_name>
      <email>Ola.Midtsether.Lian@helse-mr.no</email>
    </contact>
  </location>
  <location_countries>
    <country>Norway</country>
  </location_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>November 16, 2016</study_first_submitted>
  <study_first_submitted_qc>November 16, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 18, 2016</study_first_posted>
  <last_update_submitted>February 14, 2023</last_update_submitted>
  <last_update_submitted_qc>February 14, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 15, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Ketamine</keyword>
  <keyword>Analgesics</keyword>
  <keyword>Excitatory Amino Acid Antagonists</keyword>
  <keyword>Receptors, Glutamate</keyword>
  <keyword>Shoulder</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tendinopathy</mesh_term>
    <mesh_term>Chronic Pain</mesh_term>
    <mesh_term>Rotator Cuff Injuries</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ketamine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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/NCT02967640
org study id: 2012/1199
secondary id: 2012-002782-35
nct id: NCT02967640
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The hypothesis of the present study is that in patients with rotator cuff tendinopathy a
      specific pharmacological blocking of peripheral glutamate-receptor N-methyl-d-aspartate
      receptor type1 (NMDAR) glutamate receptors will result in pain alleviation. Activated NMDAR1
      has been demonstrated to be crucial for pain regulation in various pain disorders, and in
      biopsies from patients with tendinopathy, NMDAR1 was found to be activated.

      To test this hypothesis a specific NMDA receptor antagonist, ketalar (ketamine), will be
      injected guided by ultrasound into the subacromial space in patients with rotator cuff
      tendinopathy, and subsequently the pain response will be assessed.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Double (Participant, Outcomes Assessor)
measure: Supraspinatus pressure pain threshold
time frame: 30 minutes
description: Comparison of supraspinatus pressure pain threshold measured in Lbs/cm3, after selective N-methyl-d-aspartate receptor type 1 blocking by ketalar injection subacromially controlled against ringer acetate injection
measure: Western Ontario Rotator Cuff Index
time frame: 30 minutes
description: Comparisons of shoulder function assessed by Western Ontario Rotator Cuff index in the same patient group after selective N-methyl-d-aspartate receptor type 1 blocking by ketalar injection subacromially controlled against Ringer acetate injection.
measure: Oxford Shoulder Score
time frame: 30 minutes
description: Comparison of shoulder function assessed by Oxford Shoulder Score after selective N-methyl-d-aspartate receptor type 1 blocking by ketalar injection subacromially controlled against Ringer acetate injection.
measure: Pain
time frame: 30 minutes
description: Comparison of pain assessed by a visual analogue scale both at rest and abduction, after selective N-methyl-d-aspartate receptor type 1 blocking by ketalar injection subacromially controlled against Ringer acetate injection.
measure: Pressure pain tolerance
time frame: 30 minutes
description: Comparison of pressure pain tolerance measured in Lbs/cm3, both at rest and abduction, after selective N-methyl-d-aspartate receptor type 1 blocking by ketalar injection subacromially controlled against Ringer acetate injection.
arm group label: Ketalar
arm group type: Experimental
description: ketalar injection, subacromial
arm group label: Placebo
arm group type: Placebo Comparator
description: physiological sodium chloride (NaCl 9%) injection, subacromial
intervention type: Drug
intervention name: Ketalar
description: 2,5 ml - if well tolerated immediately followed by another 2,5 ml - of an approximately 1 mg/ml ketalar solution (1 ml of ketalar 10 mg/ml + 9 ml of NaCl 9%) injected 2 times with 1-12 weeks between each injection
arm group label: Ketalar
arm group label: Placebo
other name: Ketamine
other name: Ketanest
other name: Ketaset
other name: Calipsol
other name: Kalipsol
other name: Calypsol
intervention type: Drug
intervention name: NaCl 9%
description: 2,5 ml - if well tolerated immediately followed by another 2,5 ml - of a 9% NaCl solution injected 2 times with 1-12 weeks between each injection
arm group label: Ketalar
arm group label: Placebo
criteria: 
gender: All
minimum age: 40 Years
maximum age: N/A
healthy volunteers: No
last name: Oystein B Lian, md phd
role: Study Chair
affiliation: Helse Nord-Trøndelag HF
last name: Ola M Lian, md
phone: +47 272847
email: Ola.Midtsether.Lian@helse-mr.no
facility: 
status: Recruiting
contact: 
country: Norway
responsible party type: Sponsor
mesh term: Tendinopathy
mesh term: Chronic Pain
mesh term: Rotator Cuff Injuries
mesh term: Ketamine
sharing ipd: No