<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/NCT04485078</url>
  </required_header>
  <id_info>
    <org_study_id>09.2019.695</org_study_id>
    <nct_id>NCT04485078</nct_id>
  </id_info>
  <brief_title>Investigation of Central Sensitization Frequency and Related Factors in Axial Spondyloarthritis Patients</brief_title>
  <official_title>The Clinical and the Functional Impact of Central Sensitization On Patients With Axial Spondyloarthritis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Marmara University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Marmara University</source>
  <oversight_info>
    <has_dmc>No</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 term axial spondyloarthritis (axSpA) describes a group of chronic inflammatory diseases&#xD;
      that characterized with spinal involvement. AxSpA is one of the most common rheumatic&#xD;
      diseases and chronic pain and morning stiffness are the main complaints of these patients.&#xD;
      Central sensitization is defined as increased response to normal or sub-threshold stimuli of&#xD;
      central nervous system and its close relationship with many rheumatological diseases has been&#xD;
      demonstrated in several studies. Pain in axSpA patients is generally considered as a result&#xD;
      of increased inflammatory burden and structural changes, However, failure to adequate&#xD;
      analgesia in every patient whose inflammation is suppressed with anti-inflammatory treatment&#xD;
      suggests new pain mechanisms. Central sensitization (CS) is one of these mechanisms and its&#xD;
      recognition is only possible by detailed evaluation of the patient. There is no method for&#xD;
      the diagnosis of central sensitization is accepted as a gold standard. clinical scales and&#xD;
      quantitative sensory testing (QST) widely is used for this purpose widely. The most commonly&#xD;
      used QST types include pressure pain threshold (PPT), temporal summation (TS) and conditioned&#xD;
      pain modulation (CPM). The well-known scale used for the evaluation of central sensitization&#xD;
      is the Central Sensitization Inventory , developed by Mayer et.al in 2011 for detect central&#xD;
      sensitization in chronic pain patients. The aim of this study is to evaluate the frequency of&#xD;
      central sensitization (CS) in patients with axSpA by means of clinical scales and&#xD;
      quantitative sensory testing (QST), to examine related comorbidities and the parameters&#xD;
      associated with the development of sensitization in these patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The term axial spondyloarthritis (axSpA) describes a group of chronic inflammatory diseases&#xD;
      that characterized with spinal involvement. AxSpA is one of the most common rheumatic&#xD;
      diseases and chronic pain and morning stiffness are the main complaints of these patients.&#xD;
      Central sensitization (CS) is defined as increased response to normal or sub-threshold&#xD;
      stimuli of central nervous system and its close relationship with many rheumatological&#xD;
      diseases has been demonstrated in several studies. However, data associated with central&#xD;
      sensitization in axSpA patients is very limited. The quantitative sensory testing (QST) is&#xD;
      commonly used for detection hyperalgesia and allodynia those are accepted main findings in&#xD;
      sensitized patients. The most commonly used QST types include pressure pain threshold (PPT),&#xD;
      temporal summation (TS) and conditioned pain modulation (CPM).Pressure pain threshold&#xD;
      measurement is frequently used to show local / generalized sensitivity increase in patients&#xD;
      who develop pain sensitization. For this purpose, the pain response of superficial or deep&#xD;
      tissue can be evaluated through mechanical device called algometer. The algometer probe was&#xD;
      placed vertically in the each selected point and pressure was increased until the participant&#xD;
      reporting pressure became painful. The first pressure value at which pain is felt is&#xD;
      considered the PPT of that point. TS is defined as a progressive increase in pain response&#xD;
      with repetitive painful stimuli. This condition is also known as wind-up phenomenon and play&#xD;
      a role to development CS. CPM, known as one of the main mechanisms of endogenous analgesia,&#xD;
      is based on the principle that pain perception can be reduced with painful stimulus applied&#xD;
      to different areas according to the &quot;pain inhibits pain&quot; model. In the CPM testing, it is&#xD;
      aimed to investigate the modulator effect of two different painful stimuli on each other. The&#xD;
      diagnosis of CS can be made with QST or with Central Sensitization Inventory (CSI). The aim&#xD;
      of this study is to evaluate the frequency of central sensitization (CS) in patients with&#xD;
      axial spondyloarthritis (AxSpA) by means of clinical scales and quantitative sensory testing&#xD;
      (QST), to examine related comorbidities and the parameters associated with the development of&#xD;
      sensitization in these patients. The patients with AxSpa and healthy controls will be&#xD;
      included in this study. QST which consists of pressure pain threshold (PPT), temporal&#xD;
      summation (TS) and conditioned pain modulation (CPM) will be applied to the patient and&#xD;
      control groups. Disease activity (BASDAI), functional status (ASQoL, ILBPDI), sleep quality&#xD;
      (PSQI), pain (VAS pain), depression (BDI) and fatigue (FSS) will be assessed. Fibromyalgia&#xD;
      (FIRST) and other comorbidities will be investigated. Patients will be divided as the ones&#xD;
      with and without CS according to the central sensitization inventory (CSI) and the results&#xD;
      will be compared. After data collection, analysis will be performed with the appropriate&#xD;
      statistical method&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 20, 2019</start_date>
  <completion_date type="Actual">April 18, 2020</completion_date>
  <primary_completion_date type="Actual">February 14, 2020</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Cross-Sectional</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Central Sensitization Inventory (CSI)</measure>
    <time_frame>3 months</time_frame>
    <description>25 somatic and psychosocial symptoms, which are frequently found in patients with central sensitization in part A, are questioned. In part B, the presence of diseases whose relationship with central sensitization is well defined is questioned in the patient without participating in scoring. Central sensitization is assumed in patients who score 40 or more over 100 points.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pressure pain threshold</measure>
    <time_frame>3 months</time_frame>
    <description>The spinal hyperalgesia will be evaluated from C3 and C7 (cervical); T6 and T2 (thoracic); L3 and L5 (lumbar) levels. The PPT assessments of these levels were performed over the spinous process and 2 cm right and left side of the corresponding spinous process. The sacroiliac PPT scores were obtained from four measurement points [1]. Trapezius muscle will be used to evaluate distant control point</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Temporal summation</measure>
    <time_frame>3 months</time_frame>
    <description>TS scores will be evaluated over the trapezius muscle, sacroiliac joints, C7, T6, and L3 spine. TS scores will be calculated for each spine as the sum of three values which measured over the spinous process and 2 cm right and left side of corresponding level. In the evaluation of TS, a pressure as much the PPT value of each point will be applied with pain pressure algometer ten times with a 1-second interstimulus interval. Patients will ve asked to rate their pain using visual analogue scale (VAS) at 0, 5, and 10 seconds. TS will be calculated by subtracting the rating at 0 seconds from the rating at 10 seconds</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Conditioned pain modulation</measure>
    <time_frame>3 months</time_frame>
    <description>For the assessment of conditioned pain modulation (CPM), first stimulus will be applied to trapezius with the pressure that induced a pain intensity of 4 point on a 10 point VAS. After that the right hand of the patient will be immersed in 7 degrees Celcius water for 20 seconds to create a conditioning stimulus. Second stimulus with the same intensity of first one was applied to trapezius after the conditioning stimulus and patients asked to rate their pain. The ratio between the first and second VAS values will be defined as CPM</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>VAS pain</measure>
    <time_frame>3 months</time_frame>
    <description>The patients pain severity will be evaluated with a 10-cm horizontal visual analogue scale (VAS) ranging from &quot;0 cm&quot; (no discomfort) to &quot;10 cm&quot; (worst imaginable)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)</measure>
    <time_frame>3 months</time_frame>
    <description>BASDAI is one of the most frequently used scales for determining disease activity in axSpA patients and includes questions to evaluate the patient's axial and peripheral symptoms, fatigue and morning stiffness. The questionnaire consists of 10 questions in total and is interpreted in favor of disease activity of 4 points or more.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ankylosing Spondylitis Quality of Life Questionnaire (ASQoL)</measure>
    <time_frame>3 months</time_frame>
    <description>This scale was developed by Doward et.al in 2003 and consists of 18 questions in total. Each question is answered as yes or no, and the total score is calculated by evaluating the yes answer as 1 and no as 0. It is frequently used in clinical practice because it helps to evaluate the effects of the disease and determine treatment strategies in patients diagnosed with AxSpa.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Istanbul Low Back Pain Disability Index (ILBPDI)</measure>
    <time_frame>3 months</time_frame>
    <description>This scale was developed for assessing the severity of disability in chronic low back pain patients by Duruöz et.al in 2013. This scale consists of 18 questions in the form of a Likert scale that evaluates the limitation of daily life activities of patients in the last month.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Beck Depression Inventory (BDI)</measure>
    <time_frame>3 months</time_frame>
    <description>This questionnaire consists of 21 questions, each with four options. Scoring is interpreted as 0-9 normal, 10-18 mild depression, 19-29 moderate depression and 30-63 points as severe depression.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fatigue severity scale (FSS)</measure>
    <time_frame>3 months</time_frame>
    <description>The FSS includes 9 questions included in order to determine the negative effects of fatigue intensity and fatigue on daily life activities in the last week. İf the score more than 6.1, this is interpreted in favor of chronic fatigue syndrome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pittsburgh Sleep Quality Index (PSQI)</measure>
    <time_frame>3 months</time_frame>
    <description>This scale is designed for quantitative measurement of sleep quality and consists of 24 questions in total. The questions are divided into 7 sections those included sleep disturbance-related symptoms. High scores are associated with poor sleep quality.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fibromyalgia Rapid Screening Tool</measure>
    <time_frame>3 months</time_frame>
    <description>This questionnaire is consisted of 6 questions in which fibromyalgia-related clinical parameters are investigated. The patient scoring at least 5 points is considered has fibromyalgia.</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">150</enrollment>
  <condition>Axial Spondyloarthritis</condition>
  <condition>Central Sensitisation</condition>
  <arm_group>
    <arm_group_label>Axial spondyloarthritis patients</arm_group_label>
    <description>QST with clinical scales</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Healthy controls</arm_group_label>
    <description>QST</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Pressure pain threshold</intervention_name>
    <description>The PPT assessments of spine will be performed over the spinous process and 2 cm right and left side of the corresponding spinous process. The regional PPT scores will be composed from sum of all PPT values for related segments at spine. The sacroiliac PPT scores will be obtained bilaterally from four measurement points; the first point is located 1 cm medially and caudally from spina iliaca posterior superior (SIPS) and 3 more laterally, medially and cranially.The left trapezius muscle will be used to evaluate distant control point .The 1 cm2 algometer probe will be placed vertically in the each selected point and pressure will be increased with 0.1 kg/sc until the participant reporting pressure became painful. The pressure value at which the pain is first felt will be accepted as the PPT of that point.</description>
    <arm_group_label>Axial spondyloarthritis patients</arm_group_label>
    <arm_group_label>Healthy controls</arm_group_label>
    <other_name>PPT</other_name>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Temporal summation</intervention_name>
    <description>TS will be evaluated over the trapezius muscle, sacroiliac joints, C7, T6, and L3 levels at spine with manuel algometer. TS scores will be calculated for each spine level as the sum of three values which measured over the spinous process and 2 cm right and left side of corresponding level. In the evaluation of TS, a pressure as much the PPT value of each point will be applied with pain pressure algometer ten times with a 1-second interstimulus interval. Patients will be asked to rate their pain using on a 0 to 10 visual analogue scale (VAS) at 0, 5, and 10 seconds. TS will be calculated by subtracting the rating at 0 seconds from the rating at 10 seconds. The point that is located 1 cm medially and caudally from SIPS was used for SI joint TS measurement on both sides.</description>
    <arm_group_label>Axial spondyloarthritis patients</arm_group_label>
    <arm_group_label>Healthy controls</arm_group_label>
    <other_name>TS</other_name>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Conditioned pain modulation</intervention_name>
    <description>First stimulus will be applied to trapezius with the pressure that induced a pain intensity of 4 point on a 10 point VAS as called a test stimulus. After that the right hand of the patient will be immersed in 70C water for 20 seconds to create a conditioning stimulus. Second test stimulus with the same intensity of first one will be applied to trapezius after the conditioning stimulus and patients will be asked to rate their pain. If the patients cannot hold their hand in the water for 20 seconds, the test stimulus will be applied immediately after the patients removed their hands out of water. The ratio between the first and second VAS values multiplied by 100 will be defined as CPM score</description>
    <arm_group_label>Axial spondyloarthritis patients</arm_group_label>
    <other_name>CPM</other_name>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Central Sensitization Inventory</intervention_name>
    <description>Standardized questionnaire to determine the level of central sensitization</description>
    <arm_group_label>Axial spondyloarthritis patients</arm_group_label>
    <other_name>CSI</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Bath Ankylosing Spondylitis Disease Activity Index</intervention_name>
    <description>Standardized questionnaire to determine the level of disease activity in AxSpa patients</description>
    <arm_group_label>Axial spondyloarthritis patients</arm_group_label>
    <other_name>BASDAI</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Ankylosing Spondylitis Quality of Life</intervention_name>
    <description>Standardized questionnaire to investigate the quality of life in AxSpa patients</description>
    <arm_group_label>Axial spondyloarthritis patients</arm_group_label>
    <other_name>ASQoL</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Istanbul Low Back Pain Disability Index</intervention_name>
    <description>Standardized questionnaire to investigate the disability</description>
    <arm_group_label>Axial spondyloarthritis patients</arm_group_label>
    <other_name>ILPBDI</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Beck Depression Inventory</intervention_name>
    <description>Standardized questionnaire to investigate the depression</description>
    <arm_group_label>Axial spondyloarthritis patients</arm_group_label>
    <other_name>BDI</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Fatigue Severity Scale</intervention_name>
    <description>Standardized questionnaire to investigate the fatigue</description>
    <arm_group_label>Axial spondyloarthritis patients</arm_group_label>
    <other_name>FSS</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Pittsburgh Sleep Quality Index</intervention_name>
    <description>Standardized questionnaire to investigate the sleep quality and disturbance</description>
    <arm_group_label>Axial spondyloarthritis patients</arm_group_label>
    <other_name>PSQI</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Fibromyalgia Rapid Screening Tool</intervention_name>
    <description>Standardized questionnaire to detect fibromyalgia</description>
    <arm_group_label>Axial spondyloarthritis patients</arm_group_label>
    <other_name>FIRST</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Visual analogue scale</intervention_name>
    <description>global pain score on a 0 to 10</description>
    <arm_group_label>Axial spondyloarthritis patients</arm_group_label>
    <other_name>VAS</other_name>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        The patients aged 18-65 years diagnosed with axSpA according to the ASAS criteria will be&#xD;
        recruited from a Rheumatology outpatient clinic of a single tertiary care hospital&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Diagnosed with axSpA according to the Assessment of SpondyloArthritis International Society&#xD;
        (ASAS) criteria Aged between 18-65 years&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Had an other rheumatic diseases, peripheral vascular disease, peripheral neuropathy and&#xD;
        spine disease (e.g., symptomatic herniated disc, spinal stenosis), Using centrally acting&#xD;
        pain medications (e.g., pregabaline, duloxetine, opioids) or glucocorticoids (&gt;10 mg&#xD;
        prednisone or its equivalent) within 3 months of study enrollment&#xD;
&#xD;
        The exclusion criteria of the control grup were same as that of the patients.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Mehmet T DURUOZ, Professor</last_name>
    <role>Study Chair</role>
    <affiliation>Marmara University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Feyza Nur YUCEL</name>
      <address>
        <city>Istanbul</city>
        <zip>34100</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Turkey</country>
  </location_countries>
  <link>
    <url>https://www.iasp-pain.org/Education/Content.aspx?ItemNumber=1698#Centralsensitization</url>
    <description>IASP terminology</description>
  </link>
  <results_reference>
    <citation>Strand V, Singh JA. Patient Burden of Axial Spondyloarthritis. J Clin Rheumatol. 2017 Oct;23(7):383-391. doi: 10.1097/RHU.0000000000000589.</citation>
    <PMID>28937474</PMID>
  </results_reference>
  <results_reference>
    <citation>Rolke R, Baron R, Maier C, Tolle TR, Treede -DR, Beyer A, Binder A, Birbaumer N, Birklein F, Botefur IC, Braune S, Flor H, Huge V, Klug R, Landwehrmeyer GB, Magerl W, Maihofner C, Rolko C, Schaub C, Scherens A, Sprenger T, Valet M, Wasserka B. Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): standardized protocol and reference values. Pain. 2006 Aug;123(3):231-243. doi: 10.1016/j.pain.2006.01.041. Epub 2006 May 11. Erratum In: Pain. 2006 Nov;125(1-2):197.</citation>
    <PMID>16697110</PMID>
  </results_reference>
  <results_reference>
    <citation>Arendt-Nielsen L, Graven-Nielsen T, Svensson P, Jensen TS. Temporal summation in muscles and referred pain areas: an experimental human study. Muscle Nerve. 1997 Oct;20(10):1311-3. doi: 10.1002/(sici)1097-4598(199710)20:103.0.co;2-5.</citation>
    <PMID>9324089</PMID>
  </results_reference>
  <results_reference>
    <citation>Yarnitsky D, Bouhassira D, Drewes AM, Fillingim RB, Granot M, Hansson P, Landau R, Marchand S, Matre D, Nilsen KB, Stubhaug A, Treede RD, Wilder-Smith OH. Recommendations on practice of conditioned pain modulation (CPM) testing. Eur J Pain. 2015 Jul;19(6):805-6. doi: 10.1002/ejp.605. Epub 2014 Oct 20.</citation>
    <PMID>25330039</PMID>
  </results_reference>
  <results_reference>
    <citation>Neblett R, Cohen H, Choi Y, Hartzell MM, Williams M, Mayer TG, Gatchel RJ. The Central Sensitization Inventory (CSI): establishing clinically significant values for identifying central sensitivity syndromes in an outpatient chronic pain sample. J Pain. 2013 May;14(5):438-45. doi: 10.1016/j.jpain.2012.11.012. Epub 2013 Mar 13.</citation>
    <PMID>23490634</PMID>
  </results_reference>
  <results_reference>
    <citation>Doward LC, Spoorenberg A, Cook SA, Whalley D, Helliwell PS, Kay LJ, McKenna SP, Tennant A, van der Heijde D, Chamberlain MA. Development of the ASQoL: a quality of life instrument specific to ankylosing spondylitis. Ann Rheum Dis. 2003 Jan;62(1):20-6. doi: 10.1136/ard.62.1.20.</citation>
    <PMID>12480664</PMID>
  </results_reference>
  <results_reference>
    <citation>Duruoz MT, Ozcan E, Ketenci A, Karan A. Development and validation of a functional disability index for chronic low back pain. J Back Musculoskelet Rehabil. 2013;26(1):45-54. doi: 10.3233/BMR-2012-00349.</citation>
    <PMID>23411648</PMID>
  </results_reference>
  <results_reference>
    <citation>van Leeuwen RJ, Szadek K, de Vet H, Zuurmond W, Perez R. Pain Pressure Threshold in the Region of the Sacroiliac Joint in Patients Diagnosed with Sacroiliac Joint Pain. Pain Physician. 2016 Mar;19(3):147-54.</citation>
    <PMID>27008288</PMID>
  </results_reference>
  <results_reference>
    <citation>Middlebrook N, Heneghan NR, Evans DW, Rushton A, Falla D. Reliability of temporal summation, thermal and pressure pain thresholds in a healthy cohort and musculoskeletal trauma population. PLoS One. 2020 May 29;15(5):e0233521. doi: 10.1371/journal.pone.0233521. eCollection 2020.</citation>
    <PMID>32469913</PMID>
  </results_reference>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>July 21, 2020</study_first_submitted>
  <study_first_submitted_qc>July 21, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 24, 2020</study_first_posted>
  <last_update_submitted>August 4, 2020</last_update_submitted>
  <last_update_submitted_qc>August 4, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">August 6, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Axial spondyloarthritis</keyword>
  <keyword>central sensitization</keyword>
  <keyword>quantitative sensory testing</keyword>
  <keyword>central sensitization inventory</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Spondylitis</mesh_term>
    <mesh_term>Spondylarthritis</mesh_term>
    <mesh_term>Axial Spondyloarthritis</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT04485078
org study id: 09.2019.695
nct id: NCT04485078
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The term axial spondyloarthritis (axSpA) describes a group of chronic inflammatory diseases
      that characterized with spinal involvement. AxSpA is one of the most common rheumatic
      diseases and chronic pain and morning stiffness are the main complaints of these patients.
      Central sensitization is defined as increased response to normal or sub-threshold stimuli of
      central nervous system and its close relationship with many rheumatological diseases has been
      demonstrated in several studies. Pain in axSpA patients is generally considered as a result
      of increased inflammatory burden and structural changes, However, failure to adequate
      analgesia in every patient whose inflammation is suppressed with anti-inflammatory treatment
      suggests new pain mechanisms. Central sensitization (CS) is one of these mechanisms and its
      recognition is only possible by detailed evaluation of the patient. There is no method for
      the diagnosis of central sensitization is accepted as a gold standard. clinical scales and
      quantitative sensory testing (QST) widely is used for this purpose widely. The most commonly
      used QST types include pressure pain threshold (PPT), temporal summation (TS) and conditioned
      pain modulation (CPM). The well-known scale used for the evaluation of central sensitization
      is the Central Sensitization Inventory , developed by Mayer et.al in 2011 for detect central
      sensitization in chronic pain patients. The aim of this study is to evaluate the frequency of
      central sensitization (CS) in patients with axSpA by means of clinical scales and
      quantitative sensory testing (QST), to examine related comorbidities and the parameters
      associated with the development of sensitization in these patients.
The term axial spondyloarthritis (axSpA) describes a group of chronic inflammatory diseases
      that characterized with spinal involvement. AxSpA is one of the most common rheumatic
      diseases and chronic pain and morning stiffness are the main complaints of these patients.
      Central sensitization (CS) is defined as increased response to normal or sub-threshold
      stimuli of central nervous system and its close relationship with many rheumatological
      diseases has been demonstrated in several studies. However, data associated with central
      sensitization in axSpA patients is very limited. The quantitative sensory testing (QST) is
      commonly used for detection hyperalgesia and allodynia those are accepted main findings in
      sensitized patients. The most commonly used QST types include pressure pain threshold (PPT),
      temporal summation (TS) and conditioned pain modulation (CPM).Pressure pain threshold
      measurement is frequently used to show local / generalized sensitivity increase in patients
      who develop pain sensitization. For this purpose, the pain response of superficial or deep
      tissue can be evaluated through mechanical device called algometer. The algometer probe was
      placed vertically in the each selected point and pressure was increased until the participant
      reporting pressure became painful. The first pressure value at which pain is felt is
      considered the PPT of that point. TS is defined as a progressive increase in pain response
      with repetitive painful stimuli. This condition is also known as wind-up phenomenon and play
      a role to development CS. CPM, known as one of the main mechanisms of endogenous analgesia,
      is based on the principle that pain perception can be reduced with painful stimulus applied
      to different areas according to the "pain inhibits pain" model. In the CPM testing, it is
      aimed to investigate the modulator effect of two different painful stimuli on each other. The
      diagnosis of CS can be made with QST or with Central Sensitization Inventory (CSI). The aim
      of this study is to evaluate the frequency of central sensitization (CS) in patients with
      axial spondyloarthritis (AxSpA) by means of clinical scales and quantitative sensory testing
      (QST), to examine related comorbidities and the parameters associated with the development of
      sensitization in these patients. The patients with AxSpa and healthy controls will be
      included in this study. QST which consists of pressure pain threshold (PPT), temporal
      summation (TS) and conditioned pain modulation (CPM) will be applied to the patient and
      control groups. Disease activity (BASDAI), functional status (ASQoL, ILBPDI), sleep quality
      (PSQI), pain (VAS pain), depression (BDI) and fatigue (FSS) will be assessed. Fibromyalgia
      (FIRST) and other comorbidities will be investigated. Patients will be divided as the ones
      with and without CS according to the central sensitization inventory (CSI) and the results
      will be compared. After data collection, analysis will be performed with the appropriate
      statistical method
observational model: Case-Control
time perspective: Cross-Sectional
measure: Central Sensitization Inventory (CSI)
time frame: 3 months
description: 25 somatic and psychosocial symptoms, which are frequently found in patients with central sensitization in part A, are questioned. In part B, the presence of diseases whose relationship with central sensitization is well defined is questioned in the patient without participating in scoring. Central sensitization is assumed in patients who score 40 or more over 100 points.
measure: Pressure pain threshold
time frame: 3 months
description: The spinal hyperalgesia will be evaluated from C3 and C7 (cervical); T6 and T2 (thoracic); L3 and L5 (lumbar) levels. The PPT assessments of these levels were performed over the spinous process and 2 cm right and left side of the corresponding spinous process. The sacroiliac PPT scores were obtained from four measurement points [1]. Trapezius muscle will be used to evaluate distant control point
measure: Temporal summation
time frame: 3 months
description: TS scores will be evaluated over the trapezius muscle, sacroiliac joints, C7, T6, and L3 spine. TS scores will be calculated for each spine as the sum of three values which measured over the spinous process and 2 cm right and left side of corresponding level. In the evaluation of TS, a pressure as much the PPT value of each point will be applied with pain pressure algometer ten times with a 1-second interstimulus interval. Patients will ve asked to rate their pain using visual analogue scale (VAS) at 0, 5, and 10 seconds. TS will be calculated by subtracting the rating at 0 seconds from the rating at 10 seconds
measure: Conditioned pain modulation
time frame: 3 months
description: For the assessment of conditioned pain modulation (CPM), first stimulus will be applied to trapezius with the pressure that induced a pain intensity of 4 point on a 10 point VAS. After that the right hand of the patient will be immersed in 7 degrees Celcius water for 20 seconds to create a conditioning stimulus. Second stimulus with the same intensity of first one was applied to trapezius after the conditioning stimulus and patients asked to rate their pain. The ratio between the first and second VAS values will be defined as CPM
measure: VAS pain
time frame: 3 months
description: The patients pain severity will be evaluated with a 10-cm horizontal visual analogue scale (VAS) ranging from "0 cm" (no discomfort) to "10 cm" (worst imaginable)
measure: Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)
time frame: 3 months
description: BASDAI is one of the most frequently used scales for determining disease activity in axSpA patients and includes questions to evaluate the patient's axial and peripheral symptoms, fatigue and morning stiffness. The questionnaire consists of 10 questions in total and is interpreted in favor of disease activity of 4 points or more.
measure: Ankylosing Spondylitis Quality of Life Questionnaire (ASQoL)
time frame: 3 months
description: This scale was developed by Doward et.al in 2003 and consists of 18 questions in total. Each question is answered as yes or no, and the total score is calculated by evaluating the yes answer as 1 and no as 0. It is frequently used in clinical practice because it helps to evaluate the effects of the disease and determine treatment strategies in patients diagnosed with AxSpa.
measure: Istanbul Low Back Pain Disability Index (ILBPDI)
time frame: 3 months
description: This scale was developed for assessing the severity of disability in chronic low back pain patients by Duruöz et.al in 2013. This scale consists of 18 questions in the form of a Likert scale that evaluates the limitation of daily life activities of patients in the last month.
measure: Beck Depression Inventory (BDI)
time frame: 3 months
description: This questionnaire consists of 21 questions, each with four options. Scoring is interpreted as 0-9 normal, 10-18 mild depression, 19-29 moderate depression and 30-63 points as severe depression.
measure: Fatigue severity scale (FSS)
time frame: 3 months
description: The FSS includes 9 questions included in order to determine the negative effects of fatigue intensity and fatigue on daily life activities in the last week. İf the score more than 6.1, this is interpreted in favor of chronic fatigue syndrome.
measure: Pittsburgh Sleep Quality Index (PSQI)
time frame: 3 months
description: This scale is designed for quantitative measurement of sleep quality and consists of 24 questions in total. The questions are divided into 7 sections those included sleep disturbance-related symptoms. High scores are associated with poor sleep quality.
measure: Fibromyalgia Rapid Screening Tool
time frame: 3 months
description: This questionnaire is consisted of 6 questions in which fibromyalgia-related clinical parameters are investigated. The patient scoring at least 5 points is considered has fibromyalgia.
arm group label: Axial spondyloarthritis patients
description: QST with clinical scales
arm group label: Healthy controls
description: QST
intervention type: Diagnostic Test
intervention name: Pressure pain threshold
description: The PPT assessments of spine will be performed over the spinous process and 2 cm right and left side of the corresponding spinous process. The regional PPT scores will be composed from sum of all PPT values for related segments at spine. The sacroiliac PPT scores will be obtained bilaterally from four measurement points; the first point is located 1 cm medially and caudally from spina iliaca posterior superior (SIPS) and 3 more laterally, medially and cranially.The left trapezius muscle will be used to evaluate distant control point .The 1 cm2 algometer probe will be placed vertically in the each selected point and pressure will be increased with 0.1 kg/sc until the participant reporting pressure became painful. The pressure value at which the pain is first felt will be accepted as the PPT of that point.
arm group label: Axial spondyloarthritis patients
arm group label: Healthy controls
other name: PPT
intervention type: Diagnostic Test
intervention name: Temporal summation
description: TS will be evaluated over the trapezius muscle, sacroiliac joints, C7, T6, and L3 levels at spine with manuel algometer. TS scores will be calculated for each spine level as the sum of three values which measured over the spinous process and 2 cm right and left side of corresponding level. In the evaluation of TS, a pressure as much the PPT value of each point will be applied with pain pressure algometer ten times with a 1-second interstimulus interval. Patients will be asked to rate their pain using on a 0 to 10 visual analogue scale (VAS) at 0, 5, and 10 seconds. TS will be calculated by subtracting the rating at 0 seconds from the rating at 10 seconds. The point that is located 1 cm medially and caudally from SIPS was used for SI joint TS measurement on both sides.
arm group label: Axial spondyloarthritis patients
arm group label: Healthy controls
other name: TS
intervention type: Diagnostic Test
intervention name: Conditioned pain modulation
description: First stimulus will be applied to trapezius with the pressure that induced a pain intensity of 4 point on a 10 point VAS as called a test stimulus. After that the right hand of the patient will be immersed in 70C water for 20 seconds to create a conditioning stimulus. Second test stimulus with the same intensity of first one will be applied to trapezius after the conditioning stimulus and patients will be asked to rate their pain. If the patients cannot hold their hand in the water for 20 seconds, the test stimulus will be applied immediately after the patients removed their hands out of water. The ratio between the first and second VAS values multiplied by 100 will be defined as CPM score
arm group label: Axial spondyloarthritis patients
other name: CPM
intervention type: Diagnostic Test
intervention name: Central Sensitization Inventory
description: Standardized questionnaire to determine the level of central sensitization
arm group label: Axial spondyloarthritis patients
other name: CSI
intervention type: Other
intervention name: Bath Ankylosing Spondylitis Disease Activity Index
description: Standardized questionnaire to determine the level of disease activity in AxSpa patients
arm group label: Axial spondyloarthritis patients
other name: BASDAI
intervention type: Other
intervention name: Ankylosing Spondylitis Quality of Life
description: Standardized questionnaire to investigate the quality of life in AxSpa patients
arm group label: Axial spondyloarthritis patients
other name: ASQoL
intervention type: Other
intervention name: Istanbul Low Back Pain Disability Index
description: Standardized questionnaire to investigate the disability
arm group label: Axial spondyloarthritis patients
other name: ILPBDI
intervention type: Other
intervention name: Beck Depression Inventory
description: Standardized questionnaire to investigate the depression
arm group label: Axial spondyloarthritis patients
other name: BDI
intervention type: Other
intervention name: Fatigue Severity Scale
description: Standardized questionnaire to investigate the fatigue
arm group label: Axial spondyloarthritis patients
other name: FSS
intervention type: Other
intervention name: Pittsburgh Sleep Quality Index
description: Standardized questionnaire to investigate the sleep quality and disturbance
arm group label: Axial spondyloarthritis patients
other name: PSQI
intervention type: Other
intervention name: Fibromyalgia Rapid Screening Tool
description: Standardized questionnaire to detect fibromyalgia
arm group label: Axial spondyloarthritis patients
other name: FIRST
intervention type: Other
intervention name: Visual analogue scale
description: global pain score on a 0 to 10
arm group label: Axial spondyloarthritis patients
other name: VAS
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Mehmet T DURUOZ, Professor
role: Study Chair
affiliation: Marmara University
facility: 
country: Turkey
url: https://www.iasp-pain.org/Education/Content.aspx?ItemNumber=1698#Centralsensitization
description: IASP terminology
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PMID: 28937474
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PMID: 16697110
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PMID: 9324089
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PMID: 25330039
citation: Neblett R, Cohen H, Choi Y, Hartzell MM, Williams M, Mayer TG, Gatchel RJ. The Central Sensitization Inventory (CSI): establishing clinically significant values for identifying central sensitivity syndromes in an outpatient chronic pain sample. J Pain. 2013 May;14(5):438-45. doi: 10.1016/j.jpain.2012.11.012. Epub 2013 Mar 13.
PMID: 23490634
citation: Doward LC, Spoorenberg A, Cook SA, Whalley D, Helliwell PS, Kay LJ, McKenna SP, Tennant A, van der Heijde D, Chamberlain MA. Development of the ASQoL: a quality of life instrument specific to ankylosing spondylitis. Ann Rheum Dis. 2003 Jan;62(1):20-6. doi: 10.1136/ard.62.1.20.
PMID: 12480664
citation: Duruoz MT, Ozcan E, Ketenci A, Karan A. Development and validation of a functional disability index for chronic low back pain. J Back Musculoskelet Rehabil. 2013;26(1):45-54. doi: 10.3233/BMR-2012-00349.
PMID: 23411648
citation: van Leeuwen RJ, Szadek K, de Vet H, Zuurmond W, Perez R. Pain Pressure Threshold in the Region of the Sacroiliac Joint in Patients Diagnosed with Sacroiliac Joint Pain. Pain Physician. 2016 Mar;19(3):147-54.
PMID: 27008288
citation: Middlebrook N, Heneghan NR, Evans DW, Rushton A, Falla D. Reliability of temporal summation, thermal and pressure pain thresholds in a healthy cohort and musculoskeletal trauma population. PLoS One. 2020 May 29;15(5):e0233521. doi: 10.1371/journal.pone.0233521. eCollection 2020.
PMID: 32469913
responsible party type: Sponsor
mesh term: Spondylitis
mesh term: Spondylarthritis
mesh term: Axial Spondyloarthritis
sharing ipd: Undecided