<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/NCT01700634</url>
  </required_header>
  <id_info>
    <org_study_id>MON-SC-2012-01</org_study_id>
    <nct_id>NCT01700634</nct_id>
  </id_info>
  <brief_title>fMRI Evaluation of Pain Central Sensitization Phenomena in Subjects With Knee Osteoarthritis</brief_title>
  <official_title>fMRI Evaluation of Pain Central Sensitization Phenomena in Subjects With Knee Osteoarthritis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Parc de Salut Mar</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Parc de Salut Mar</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The aim of this project is to investigate fMRI ability to identify pain central sensitization&#xD;
      in chronic knee OA. Patients with high and low central sensitization and healthy control&#xD;
      subjects will be included. Central sensitization will be clinically defined based on the&#xD;
      evidence of regional spread of pain (spreading sensitization) and increased pain response to&#xD;
      repeated stimulation (temporal summation). Operatively, a patient will be assigned to high&#xD;
      sensitization group when showing (i) clinical evidence of pain or altered sensations spread&#xD;
      beyond the knee joint by manual palpation, (ii) a minimum of 3 anatomical sites around the&#xD;
      knee showing a pressure pain threshold below 4 kg/cm2 (tender points), (iii) pain score of 4&#xD;
      points or more in a 11-point scale during 4 kg/cm2 pressure stimulation on the&#xD;
      anterior/medial surface of the tibial bone (the site selected for the fMRI experiment) and&#xD;
      (iv) increase of at least 1 point in a 11-point scale after 10 repeated pressure stimulation&#xD;
      on the tenderest point around the knee.&#xD;
&#xD;
      A three-step strategy is proposed to characterize the phenomenon by assessing (i) brain&#xD;
      response to direct pressure stimulation on the painful knee, which will reflect the&#xD;
      combination of peripheral and central sensitization; (ii) brain response to pressure&#xD;
      stimulation on a non-arthritic hyperalgesic area (i.e., the anterior surface of the tibia),&#xD;
      which will mostly reflect central sensitization mediated at the spinal cord level, and (iii)&#xD;
      brain response to moderately painful heat stimulation on a healthy skin area (i.e., volar&#xD;
      forearm), which will reflect central sensitization occurring in the brain and involving the&#xD;
      highest-level pain modulatory mechanisms. An additional evaluation is proposed using&#xD;
      resting-state fMRI to assess potential alterations in baseline brain functional organization.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>September 2012</start_date>
  <completion_date type="Actual">October 2016</completion_date>
  <primary_completion_date type="Actual">July 2014</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Crossover</observational_model>
    <time_perspective>Cross-Sectional</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Blood oxygenation level dependent (BOLD) in response to pressure stimuli applied to the knee using fMRI</measure>
    <time_frame>Baseline</time_frame>
    <description>BOLD in response to pressure stimuli applied to the knee assessed using fMRI, that measures endogenous haemodynamic signal reflecting blood oxygenation changes linked to neuronal activity.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>BOLD in response to painful contact heat stimuli applied to healthy forearm skin assessed using fMRI</measure>
    <time_frame>Baseline</time_frame>
    <description>BOLD in response to painful contact heat stimuli applied to healthy forearm skin assessed using fMRI, that measures endogenous haemodynamic signal reflecting blood oxygenation changes linked to neuronal activity.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>BOLD during resting-state using fMRI</measure>
    <time_frame>Baseline</time_frame>
    <description>BOLD during resting-state using fMRI, that measures endogenous haemodynamic signal reflecting blood oxygenation changes linked to neuronal activity.</description>
  </secondary_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Actual">90</enrollment>
  <condition>Osteoarthritis</condition>
  <arm_group>
    <arm_group_label>OA patients with HIGH central sensitization</arm_group_label>
    <description>Central sensitization will be defined by the presence of both spreading sensitization and temporal summation to repeated pressure pain stimulation (Arendt-Nielsen et al. 2010, Graven-Nielsen et al. 2010, Woolf 2010, Imamura et al. 2008, Nijs et al. 2010).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>OA patients with LOW central sensitization</arm_group_label>
  </arm_group>
  <arm_group>
    <arm_group_label>Control subjects</arm_group_label>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        Patients with HIGH / LOW central sensitation, and control subjects.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients:&#xD;
&#xD;
               1. A diagnosis of knee OA and suitable for the study as determined by a responsible&#xD;
                  physician, based on a medical evaluation including medical history, physical&#xD;
                  examination, laboratory tests and cardiac monitoring.&#xD;
&#xD;
               2. Have a radiological and clinical diagnosis of knee OA based upon American College&#xD;
                  of Rheumatology (ACR) criteria (1986) affecting at least one knee of a minimum of&#xD;
                  3 months in symptom duration prior to screening.&#xD;
&#xD;
               3. Subject is either male or female and at least 45 years of age.&#xD;
&#xD;
               4. A minimum of 4 out of 10 on the numerical rating scale (Brief Pain Inventory- BPI&#xD;
                  item 5) at screening and/ or a requirement for the use of an analgesic for the&#xD;
                  pain in the OA knee. In addition, baseline pain must be stable for at least 72&#xD;
                  hours prior to fMRI assessment or fMRI assessment may be delayed.&#xD;
&#xD;
               5. A maximum of 8 out of 10 on the NRS at screening. Enrolment may be delayed if, in&#xD;
                  the opinion of the investigator, the severity of pain represents an isolated&#xD;
                  incident.&#xD;
&#xD;
               6. A female subject is eligible to participate if she is of non-childbearing&#xD;
                  potential.&#xD;
&#xD;
               7. Body weight &lt;120kg.&#xD;
&#xD;
               8. Capable of giving written informed consent, which includes compliance with the&#xD;
                  requirements and restrictions listed in the consent form.&#xD;
&#xD;
               9. Subject demonstrates an understanding of the study and a willingness to&#xD;
                  participate as evidenced by voluntary written informed consent.&#xD;
&#xD;
          -  Controls:&#xD;
&#xD;
               1. Subject is either male or female and at least 45 years of age.&#xD;
&#xD;
               2. Absence of clinically relevant neurologic and psychiatric disease and history of&#xD;
                  head trauma with loss of consciousness.&#xD;
&#xD;
               3. Absence of non-compensated medical diseases and pain disorders that may&#xD;
                  relevantly affect brain function and pain perception.&#xD;
&#xD;
               4. No clinical evidence of knee OA.&#xD;
&#xD;
               5. A female subject is eligible to participate if she is of non-childbearing&#xD;
                  potential.&#xD;
&#xD;
               6. Body weight &lt;120kg.&#xD;
&#xD;
               7. Capable of giving written informed consent, which includes compliance with the&#xD;
                  requirements and restrictions listed in the consent form.&#xD;
&#xD;
               8. Subject demonstrates an understanding of the study and a willingness to&#xD;
                  participate as evidenced by voluntary written informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. - Subjects will not be permitted to heavily exercise for 12 hours prior to fMRI&#xD;
             assessment&#xD;
&#xD;
          2. - Subjects will be required to refrain from the following treatments: I.- Analgesic&#xD;
             and anti-inflammatory drugs for 3 days prior to fMRI assessment except for rescue&#xD;
             medication. Rescue medication will be based on paracetamol (dosed 1g/8h), which in any&#xD;
             case must be withdrawn for a minimum of 24 h prior to fMRI assessment or the fMRI&#xD;
             assessment may be delayed.&#xD;
&#xD;
        II.- Steroid injections into the joint or muscle for three months prior to fMRI assessment&#xD;
        III.- Hyaluronan injections into index knee within the previous 6 months prior fMRI&#xD;
        assessment IV.- Non-pharmacological treatments, such as heat wraps or massage for 24 hours&#xD;
        prior to fMRI assessment.&#xD;
&#xD;
        V.- Antidepressants not allowed: MAOIs, Tricyclic antidepressants, mixed 5HT &amp; NE reuptake&#xD;
        inhibitors (eg. Duloxetine). SISR are not allowed as a recent prescription, moreover they&#xD;
        are allowed in case of chronic use (more than 6 weeks). If those drugs are used for less&#xD;
        than 6 weeks, patients could participate in the study after a washout period.&#xD;
&#xD;
        VI.- Anticonvulsant indicated as a pain killer are not allowed, but patients could&#xD;
        participate in the study after a washout period.&#xD;
&#xD;
        VII.- Patients can take low doses of hypnotic drugs (eg. Lorazepam 1mg/OD or Diazepam&#xD;
        5mg/OD) if they are used as a chronic prescription (more than 6 weeks). If they are used&#xD;
        for less than 6 weeks, patients could participate in the study after a washout period.&#xD;
&#xD;
        Subjects will be allowed to take their chronic (non-analgesic and non-anti-inflammatory)&#xD;
        medications if the treatments have been used continuously for at least six weeks prior to&#xD;
        assessment.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>45 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Jordi Monfort Faure</name>
      <address>
        <city>Barcelona</city>
        <zip>08003</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
  <verification_date>October 2016</verification_date>
  <study_first_submitted>October 2, 2012</study_first_submitted>
  <study_first_submitted_qc>October 2, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 4, 2012</study_first_posted>
  <last_update_submitted>October 4, 2016</last_update_submitted>
  <last_update_submitted_qc>October 4, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">October 5, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Parc de Salut Mar</investigator_affiliation>
    <investigator_full_name>Jordi Monfort</investigator_full_name>
    <investigator_title>MD</investigator_title>
  </responsible_party>
  <keyword>fMRI, BOLD, pressure stimuli</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Osteoarthritis</mesh_term>
    <mesh_term>Osteoarthritis, Knee</mesh_term>
  </condition_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/NCT01700634
org study id: MON-SC-2012-01
nct id: NCT01700634
lead sponsor: 
has dmc: No
The aim of this project is to investigate fMRI ability to identify pain central sensitization
      in chronic knee OA. Patients with high and low central sensitization and healthy control
      subjects will be included. Central sensitization will be clinically defined based on the
      evidence of regional spread of pain (spreading sensitization) and increased pain response to
      repeated stimulation (temporal summation). Operatively, a patient will be assigned to high
      sensitization group when showing (i) clinical evidence of pain or altered sensations spread
      beyond the knee joint by manual palpation, (ii) a minimum of 3 anatomical sites around the
      knee showing a pressure pain threshold below 4 kg/cm2 (tender points), (iii) pain score of 4
      points or more in a 11-point scale during 4 kg/cm2 pressure stimulation on the
      anterior/medial surface of the tibial bone (the site selected for the fMRI experiment) and
      (iv) increase of at least 1 point in a 11-point scale after 10 repeated pressure stimulation
      on the tenderest point around the knee.

      A three-step strategy is proposed to characterize the phenomenon by assessing (i) brain
      response to direct pressure stimulation on the painful knee, which will reflect the
      combination of peripheral and central sensitization; (ii) brain response to pressure
      stimulation on a non-arthritic hyperalgesic area (i.e., the anterior surface of the tibia),
      which will mostly reflect central sensitization mediated at the spinal cord level, and (iii)
      brain response to moderately painful heat stimulation on a healthy skin area (i.e., volar
      forearm), which will reflect central sensitization occurring in the brain and involving the
      highest-level pain modulatory mechanisms. An additional evaluation is proposed using
      resting-state fMRI to assess potential alterations in baseline brain functional organization.
observational model: Case-Crossover
time perspective: Cross-Sectional
measure: Blood oxygenation level dependent (BOLD) in response to pressure stimuli applied to the knee using fMRI
time frame: Baseline
description: BOLD in response to pressure stimuli applied to the knee assessed using fMRI, that measures endogenous haemodynamic signal reflecting blood oxygenation changes linked to neuronal activity.
measure: BOLD in response to painful contact heat stimuli applied to healthy forearm skin assessed using fMRI
time frame: Baseline
description: BOLD in response to painful contact heat stimuli applied to healthy forearm skin assessed using fMRI, that measures endogenous haemodynamic signal reflecting blood oxygenation changes linked to neuronal activity.
measure: BOLD during resting-state using fMRI
time frame: Baseline
description: BOLD during resting-state using fMRI, that measures endogenous haemodynamic signal reflecting blood oxygenation changes linked to neuronal activity.
arm group label: OA patients with HIGH central sensitization
description: Central sensitization will be defined by the presence of both spreading sensitization and temporal summation to repeated pressure pain stimulation (Arendt-Nielsen et al. 2010, Graven-Nielsen et al. 2010, Woolf 2010, Imamura et al. 2008, Nijs et al. 2010).
arm group label: OA patients with LOW central sensitization
arm group label: Control subjects
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 45 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: Spain
responsible party type: Principal Investigator
investigator affiliation: Parc de Salut Mar
investigator full name: Jordi Monfort
investigator title: MD
mesh term: Osteoarthritis
mesh term: Osteoarthritis, Knee