<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/NCT01717430</url>
  </required_header>
  <id_info>
    <org_study_id>B2012:062</org_study_id>
    <nct_id>NCT01717430</nct_id>
  </id_info>
  <brief_title>Metabolic and Endocrine Effects of Repeated Epidural and Sacroiliac Joint Corticosteroid Injections</brief_title>
  <official_title>Repeated Epidural and Sacroiliac Joint Glucocorticoid Injections and Their Effect on Hypothalamic-Pituitary-Adrenal Axis Suppression and Metabolic Status</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Manitoba</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Manitoba</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Corticosteroid injections into the epidural space or sacroiliac joint are increasingly used&#xD;
      for the treatment of chronic neck, low back, and leg pain. These injections may have several&#xD;
      side effects, including suppression of the body's adrenal glands to produce steroids (adrenal&#xD;
      suppression) and negative effects on metabolism (weight gain, increased blood pressure, and&#xD;
      high blood sugar levels).&#xD;
&#xD;
      The purpose of this study is to determine the time course and predictors of adrenal&#xD;
      suppression and the metabolic effects of corticosteroid injections for chronic pain.&#xD;
&#xD;
      The investigators hypothesize normalization of adrenal function to occur within three weeks&#xD;
      of injection in most individuals. An increased frequency of injections is predicted to lead&#xD;
      to prolonged adrenal suppression. Corticosteroid injections are also hypothesized to lead to&#xD;
      increases in body weight, blood pressure, and blood sugar levels, particularly in diabetic&#xD;
      individuals.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Interventional pain procedures using corticosteroid injections (CIs), such as epidural&#xD;
      steroid injections (ESIs) and sacroiliac joint injections (SIJIs), may have adverse metabolic&#xD;
      and endocrine effects, including suppression of the hypothalamic-pituitary-adrenal axis&#xD;
      (HPAA), hypertension, weight gain, and hyperglycemia. Based on sparse data on these adverse&#xD;
      effects following repeated, long-term CIs, current guidelines suggest a maximum frequency of&#xD;
      four to six injections annually, even though patients may benefit from more frequent&#xD;
      treatments.&#xD;
&#xD;
      This prospective cohort study will follow first-time or repeat ESI or SIJI patients receiving&#xD;
      injections with 0.5 mL bupivacaine 0.25% and 15 mg dexamethasone sodium phosphate at a&#xD;
      maximum frequency of once every six weeks in order to:&#xD;
&#xD;
        -  determine the frequency and duration of HPAA suppression;&#xD;
&#xD;
        -  determine the incidence and predictors of prolonged (≥ 3 weeks) HPAA suppression;&#xD;
&#xD;
        -  determine the baseline incidence and predictors of HPAA suppression in chronic pain&#xD;
           patients presenting for their first CI; and&#xD;
&#xD;
        -  determine the effect of CIs on body weight, resting blood pressure, and glycemic control&#xD;
           over a six-month period.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>October 2012</start_date>
  <completion_date type="Anticipated">December 2016</completion_date>
  <primary_completion_date type="Anticipated">June 2016</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Time to Normalization of Hypothalamic-Pituitary-Adrenal Axis (HPAA) Function Following Epidural or Sacroiliac Joint Corticosteroid Injection</measure>
    <time_frame>From date of enrollment (Baseline) until the date of HPAA normalization assessed every 3 weeks up to 6 months</time_frame>
    <description>The high-dose rapid adrenocorticotropic hormone (ACTH) stimulation test will be performed to determine if HPAA suppression is present. Serum cortisol will be measured by electrochemiluminescence immunoassay immediately prior to and at 30 and 60 min following injection of 250 mcg cosyntropin IV. A serum cortisol level &lt;550 nmol/L (&lt;20 mcg/dL) at either time point following cosyntropin administration will designate HPAA suppression.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of Hypothalamic-Pituitary-Adrenal Axis (HPAA) Suppression in Patients Presenting for Corticosteroid Injection</measure>
    <time_frame>Baseline</time_frame>
    <description>The high-dose rapid ACTH stimulation test will be performed at Baseline to determine if HPAA suppression is present in patients presenting for corticosteroid injection.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Prolonged (≥ 3 weeks) Hypothalamic-Pituitary-Adrenal Axis (HPAA) Suppression Following Corticosteroid Injection</measure>
    <time_frame>From date of injection until the date of HPAA normalization assessed every 3 weeks up to 6 months</time_frame>
    <description>The high-dose rapid ACTH stimulation test will be performed to determine if HPAA suppression is present.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Glycosylated HbA1c (%) from Baseline to 3 months</measure>
    <time_frame>Baseline and 3 months</time_frame>
    <description>Percent glycosylated hemoglobin (HbA1c [%]) will be measured by turbidimetric inhibition immunoassay.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Glycosylated HbA1c (%) from Baseline to 6 months</measure>
    <time_frame>Baseline and 6 months</time_frame>
    <description>Percent glycosylated hemoglobin (HbA1c [%]) will be measured by turbidimetric inhibition immunoassay.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Systolic Blood Pressure from Baseline to 3 weeks</measure>
    <time_frame>Baseline and 3 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Systolic Blood Pressure from Baseline to 6 weeks</measure>
    <time_frame>Baseline and 6 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Systolic Blood Pressure from Baseline to 3 months</measure>
    <time_frame>Baseline and 3 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Systolic Blood Pressure from Baseline to 6 months</measure>
    <time_frame>Baseline and 6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Diastolic Blood Pressure from Baseline to 3 weeks</measure>
    <time_frame>Baseline and 3 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Diastolic Blood Pressure from Baseline to 6 weeks</measure>
    <time_frame>Baseline and 6 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Diastolic Blood Pressure from Baseline to 3 months</measure>
    <time_frame>Baseline and 3 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Diastolic Blood Pressure from Baseline to 6 months</measure>
    <time_frame>Baseline and 6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Body Weight from Baseline to 3 weeks</measure>
    <time_frame>Baseline and 3 weeks</time_frame>
    <description>Percent Change in Body Weight</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Body Weight from Baseline to 6 weeks</measure>
    <time_frame>Baseline and 6 weeks</time_frame>
    <description>Percent Change in Body Weight</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Body Weight from Baseline to 3 months</measure>
    <time_frame>Baseline and 3 months</time_frame>
    <description>Percent Change in Body Weight</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Body Weight from Baseline to 6 months</measure>
    <time_frame>Baseline and 6 months</time_frame>
    <description>Percent Change in Body Weight</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Pain Visual Analogue Scale (PVAS)</measure>
    <time_frame>Baseline and 3, 6, 12, and 24 weeks</time_frame>
    <description>11-point scale for average pain intensity over the preceding week. Completed at Baseline, at 3 weeks following any corticosteroid injection, and at weeks 6, 12, and 24.</description>
  </other_outcome>
  <other_outcome>
    <measure>Functional Capacity Visual Analogue Scale (FVAS)</measure>
    <time_frame>Baseline and 3, 6, 12, and 24 weeks</time_frame>
    <description>11-point scale for average functional impairment over the preceding week. Completed at Baseline, at 3 weeks following any corticosteroid injection, and at weeks 6, 12, and 24.</description>
  </other_outcome>
  <other_outcome>
    <measure>Brief Pain Inventory Short Form (BPI-SF) Pain Severity and Interference Scores</measure>
    <time_frame>Baseline and 3, 6, 12, and 24 weeks</time_frame>
    <description>Completed at Baseline, at 3 weeks following any corticosteroid injection, and at weeks 6, 12, and 24.</description>
  </other_outcome>
  <other_outcome>
    <measure>Medical Outcome Study Short Form 36 (SF-36) Health Survey Scores</measure>
    <time_frame>Baseline and 3, 6, 12, and 24 weeks</time_frame>
    <description>Completed at Baseline, at 3 weeks following any corticosteroid injection, and at weeks 6, 12, and 24.</description>
  </other_outcome>
  <other_outcome>
    <measure>Oswestry Disability Index (ODI) v2.0 Scores</measure>
    <time_frame>Baseline and 3, 6, 12, and 24 weeks</time_frame>
    <description>Completed at Baseline, at 3 weeks following any corticosteroid injection, and at weeks 6, 12, and 24.</description>
  </other_outcome>
  <other_outcome>
    <measure>North American Spine Society Patient Satisfaction Index (PSI)</measure>
    <time_frame>Baseline and 3, 6, 12, and 24 weeks</time_frame>
    <description>Completed at Baseline (for patients with previous corticosteroid injections), at 3 weeks following any corticosteroid injection, and at weeks 6, 12, and 24.</description>
  </other_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">126</enrollment>
  <condition>Neck Pain</condition>
  <condition>Back Pain</condition>
  <arm_group>
    <arm_group_label>Corticosteroid injection</arm_group_label>
    <description>Consecutive patients receiving initial or repeated sacroiliac joint or single or multi-level epidural corticosteroid injections as part of their management plan for SI joint, neck, back, or radicular pain. Injections will be performed using 0.5 mL bupivacaine 0.25% and 15 mg dexamethasone sodium phosphate.</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        Patients receiving initial or repeated sacroiliac (SI) joint injections or single- or&#xD;
        multi-level epidural injections with corticosteroids as part of their management plan for&#xD;
        chronic SI joint, neck, back, or radicular pain.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients receiving SI joint or epidural corticosteroid injections&#xD;
&#xD;
          -  At least 18 years of age&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Contraindication to corticosteroid injection (infection; pregnancy; uncontrolled&#xD;
             diabetes mellitus [per patient's report]; active congestive heart failure;&#xD;
             coagulopathy; medical conditions that prohibit holding anticoagulant or antiplatelet&#xD;
             therapy, with the exception of aspirin, for at least two weeks prior to injection; and&#xD;
             allergy to iodinated contrast dye, corticosteroids, or amide local anesthetics)&#xD;
&#xD;
          -  Known disorder of the hypothalamic-pituitary-adrenal axis&#xD;
&#xD;
          -  Corticosteroid injection within 6 weeks of study enrollment&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ryan J Amadeo, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Manitoba</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Ryan J Amadeo, MD</last_name>
    <phone>204-787-1414</phone>
    <email>ramadeo@shaw.ca</email>
  </overall_contact>
  <location>
    <facility>
      <name>Health Sciences Centre</name>
      <address>
        <city>Winnipeg</city>
        <state>Manitoba</state>
        <zip>R3Y 1X1</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Maria Loureiro</last_name>
      <phone>204-787-2404</phone>
      <email>healthtrials@hsc.mb.ca</email>
    </contact>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>December 2014</verification_date>
  <study_first_submitted>October 8, 2012</study_first_submitted>
  <study_first_submitted_qc>October 25, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 30, 2012</study_first_posted>
  <last_update_submitted>December 10, 2014</last_update_submitted>
  <last_update_submitted_qc>December 10, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">December 12, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Manitoba</investigator_affiliation>
    <investigator_full_name>Dr. Ryan Amadeo</investigator_full_name>
    <investigator_title>Assistant Professor</investigator_title>
  </responsible_party>
  <keyword>Injections, epidural</keyword>
  <keyword>Injections, intra-articular</keyword>
  <keyword>Chronic pain</keyword>
  <keyword>Neck pain</keyword>
  <keyword>Back pain</keyword>
  <keyword>Low back pain</keyword>
  <keyword>Sciatica</keyword>
  <keyword>Sacroiliac joint</keyword>
  <keyword>Corticosteroids</keyword>
  <keyword>Dexamethasone</keyword>
  <keyword>Adrenocorticotropic hormone</keyword>
  <keyword>Adrenal insufficiency</keyword>
  <keyword>Hemoglobin A, glycosylated</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Back Pain</mesh_term>
    <mesh_term>Neck Pain</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/NCT01717430
org study id: B2012:062
nct id: NCT01717430
lead sponsor: 
has dmc: No
Corticosteroid injections into the epidural space or sacroiliac joint are increasingly used
      for the treatment of chronic neck, low back, and leg pain. These injections may have several
      side effects, including suppression of the body's adrenal glands to produce steroids (adrenal
      suppression) and negative effects on metabolism (weight gain, increased blood pressure, and
      high blood sugar levels).

      The purpose of this study is to determine the time course and predictors of adrenal
      suppression and the metabolic effects of corticosteroid injections for chronic pain.

      The investigators hypothesize normalization of adrenal function to occur within three weeks
      of injection in most individuals. An increased frequency of injections is predicted to lead
      to prolonged adrenal suppression. Corticosteroid injections are also hypothesized to lead to
      increases in body weight, blood pressure, and blood sugar levels, particularly in diabetic
      individuals.
Interventional pain procedures using corticosteroid injections (CIs), such as epidural
      steroid injections (ESIs) and sacroiliac joint injections (SIJIs), may have adverse metabolic
      and endocrine effects, including suppression of the hypothalamic-pituitary-adrenal axis
      (HPAA), hypertension, weight gain, and hyperglycemia. Based on sparse data on these adverse
      effects following repeated, long-term CIs, current guidelines suggest a maximum frequency of
      four to six injections annually, even though patients may benefit from more frequent
      treatments.

      This prospective cohort study will follow first-time or repeat ESI or SIJI patients receiving
      injections with 0.5 mL bupivacaine 0.25% and 15 mg dexamethasone sodium phosphate at a
      maximum frequency of once every six weeks in order to:

        -  determine the frequency and duration of HPAA suppression;

        -  determine the incidence and predictors of prolonged (≥ 3 weeks) HPAA suppression;

        -  determine the baseline incidence and predictors of HPAA suppression in chronic pain
           patients presenting for their first CI; and

        -  determine the effect of CIs on body weight, resting blood pressure, and glycemic control
           over a six-month period.
observational model: Cohort
time perspective: Prospective
measure: Time to Normalization of Hypothalamic-Pituitary-Adrenal Axis (HPAA) Function Following Epidural or Sacroiliac Joint Corticosteroid Injection
time frame: From date of enrollment (Baseline) until the date of HPAA normalization assessed every 3 weeks up to 6 months
description: The high-dose rapid adrenocorticotropic hormone (ACTH) stimulation test will be performed to determine if HPAA suppression is present. Serum cortisol will be measured by electrochemiluminescence immunoassay immediately prior to and at 30 and 60 min following injection of 250 mcg cosyntropin IV. A serum cortisol level <550 nmol/L (<20 mcg/dL) at either time point following cosyntropin administration will designate HPAA suppression.
measure: Incidence of Hypothalamic-Pituitary-Adrenal Axis (HPAA) Suppression in Patients Presenting for Corticosteroid Injection
time frame: Baseline
description: The high-dose rapid ACTH stimulation test will be performed at Baseline to determine if HPAA suppression is present in patients presenting for corticosteroid injection.
measure: Incidence of Prolonged (≥ 3 weeks) Hypothalamic-Pituitary-Adrenal Axis (HPAA) Suppression Following Corticosteroid Injection
time frame: From date of injection until the date of HPAA normalization assessed every 3 weeks up to 6 months
description: The high-dose rapid ACTH stimulation test will be performed to determine if HPAA suppression is present.
measure: Change in Glycosylated HbA1c (%) from Baseline to 3 months
time frame: Baseline and 3 months
description: Percent glycosylated hemoglobin (HbA1c [%]) will be measured by turbidimetric inhibition immunoassay.
measure: Change in Glycosylated HbA1c (%) from Baseline to 6 months
time frame: Baseline and 6 months
description: Percent glycosylated hemoglobin (HbA1c [%]) will be measured by turbidimetric inhibition immunoassay.
measure: Change in Systolic Blood Pressure from Baseline to 3 weeks
time frame: Baseline and 3 weeks
measure: Change in Systolic Blood Pressure from Baseline to 6 weeks
time frame: Baseline and 6 weeks
measure: Change in Systolic Blood Pressure from Baseline to 3 months
time frame: Baseline and 3 months
measure: Change in Systolic Blood Pressure from Baseline to 6 months
time frame: Baseline and 6 months
measure: Change in Diastolic Blood Pressure from Baseline to 3 weeks
time frame: Baseline and 3 weeks
measure: Change in Diastolic Blood Pressure from Baseline to 6 weeks
time frame: Baseline and 6 weeks
measure: Change in Diastolic Blood Pressure from Baseline to 3 months
time frame: Baseline and 3 months
measure: Change in Diastolic Blood Pressure from Baseline to 6 months
time frame: Baseline and 6 months
measure: Change in Body Weight from Baseline to 3 weeks
time frame: Baseline and 3 weeks
description: Percent Change in Body Weight
measure: Change in Body Weight from Baseline to 6 weeks
time frame: Baseline and 6 weeks
description: Percent Change in Body Weight
measure: Change in Body Weight from Baseline to 3 months
time frame: Baseline and 3 months
description: Percent Change in Body Weight
measure: Change in Body Weight from Baseline to 6 months
time frame: Baseline and 6 months
description: Percent Change in Body Weight
measure: Pain Visual Analogue Scale (PVAS)
time frame: Baseline and 3, 6, 12, and 24 weeks
description: 11-point scale for average pain intensity over the preceding week. Completed at Baseline, at 3 weeks following any corticosteroid injection, and at weeks 6, 12, and 24.
measure: Functional Capacity Visual Analogue Scale (FVAS)
time frame: Baseline and 3, 6, 12, and 24 weeks
description: 11-point scale for average functional impairment over the preceding week. Completed at Baseline, at 3 weeks following any corticosteroid injection, and at weeks 6, 12, and 24.
measure: Brief Pain Inventory Short Form (BPI-SF) Pain Severity and Interference Scores
time frame: Baseline and 3, 6, 12, and 24 weeks
description: Completed at Baseline, at 3 weeks following any corticosteroid injection, and at weeks 6, 12, and 24.
measure: Medical Outcome Study Short Form 36 (SF-36) Health Survey Scores
time frame: Baseline and 3, 6, 12, and 24 weeks
description: Completed at Baseline, at 3 weeks following any corticosteroid injection, and at weeks 6, 12, and 24.
measure: Oswestry Disability Index (ODI) v2.0 Scores
time frame: Baseline and 3, 6, 12, and 24 weeks
description: Completed at Baseline, at 3 weeks following any corticosteroid injection, and at weeks 6, 12, and 24.
measure: North American Spine Society Patient Satisfaction Index (PSI)
time frame: Baseline and 3, 6, 12, and 24 weeks
description: Completed at Baseline (for patients with previous corticosteroid injections), at 3 weeks following any corticosteroid injection, and at weeks 6, 12, and 24.
arm group label: Corticosteroid injection
description: Consecutive patients receiving initial or repeated sacroiliac joint or single or multi-level epidural corticosteroid injections as part of their management plan for SI joint, neck, back, or radicular pain. Injections will be performed using 0.5 mL bupivacaine 0.25% and 15 mg dexamethasone sodium phosphate.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Ryan J Amadeo, MD
role: Principal Investigator
affiliation: University of Manitoba
last name: Ryan J Amadeo, MD
phone: 204-787-1414
email: ramadeo@shaw.ca
facility: 
status: Recruiting
contact: 
country: Canada
responsible party type: Principal Investigator
investigator affiliation: University of Manitoba
investigator full name: Dr. Ryan Amadeo
investigator title: Assistant Professor
mesh term: Back Pain
mesh term: Neck Pain