<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/NCT03267277</url>
  </required_header>
  <id_info>
    <org_study_id>170161</org_study_id>
    <secondary_id>17-E-0161</secondary_id>
    <nct_id>NCT03267277</nct_id>
  </id_info>
  <brief_title>Sodium Thiosulfate for Treatment of Calcinosis Associated With Juvenile and Adult Dermatomyositis</brief_title>
  <official_title>An Open-label Study of Sodium Thiosulfate for Treatment of Calcinosis Associated With Juvenile and Adult Dermatomyositis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Institute of Environmental Health Sciences (NIEHS)</agency>
      <agency_class>NIH</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Institutes of Health Clinical Center (CC)</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Background:&#xD;
&#xD;
      Dermatomyositis (DM) and juvenile dermatomyositis (JDM) cause inflammation in the muscles.&#xD;
      People with DM and JDM can develop calcium deposits in places they should not, known as&#xD;
      calcinosis. Calcinosis can be painful and cause disabilities and other problems. Researchers&#xD;
      want to learn more about calcinosis to find treatments for it.&#xD;
&#xD;
      Objective:&#xD;
&#xD;
      To test if sodium thiosulfate (STS) can treat people with DM with calcinosis.&#xD;
&#xD;
      Eligibility:&#xD;
&#xD;
      People ages 7 and older who have moderate or severe calcinosis. They must have stable DM and&#xD;
      calcium deposits in the torso or at least 2 limbs.&#xD;
&#xD;
      Design:&#xD;
&#xD;
      Participants will be screened with:&#xD;
&#xD;
        -  Medical history&#xD;
&#xD;
        -  Physical exam&#xD;
&#xD;
        -  Muscle strength and function tests&#xD;
&#xD;
        -  Blood and urine tests&#xD;
&#xD;
      Participants will have several visits:&#xD;
&#xD;
        -  7-day pre-treatment visit about 10 weeks before starting STS&#xD;
&#xD;
        -  Treatment visits over 10 weeks. They will get STS 3 times a week through IV infusion.&#xD;
           They may be hospitalized the whole time. If they tolerate the drug, they may be&#xD;
           discharged at certain times. During these times, they will return for the infusions.&#xD;
&#xD;
        -  3- to 5-day post-treatment visits 24 weeks and 62 weeks after starting STS.&#xD;
&#xD;
      Visits may include repeats of screening tests and:&#xD;
&#xD;
        -  Questionnaires&#xD;
&#xD;
        -  Scans: They lie in a machine that takes pictures of the body. They may be injected with&#xD;
           a radioactive agent.&#xD;
&#xD;
        -  Durometry: A small instrument applies pressure on the skin or exposed calcinosis.&#xD;
&#xD;
        -  Measurements of blood flow in the arms and fingernail blood vessels&#xD;
&#xD;
        -  Photographs of the skin&#xD;
&#xD;
        -  Kidney ultrasound&#xD;
&#xD;
        -  Tests of kidney function&#xD;
&#xD;
        -  Calcinosis aspiration: A needle placed into areas of calcinosis removes liquid.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Calcinosis, a serious complication of dermatomyositis, involves deposition of calcium&#xD;
      (carbonate apatite) in soft tissue, and can result in negative impacts on quality of life and&#xD;
      physical function. To date, there are no known effective therapies that are approved for the&#xD;
      treatment of dermatomyositis-associated calcinosis, and there is no consensus within the&#xD;
      medical community on the optimum treatment strategy for this often-debilitating condition.&#xD;
&#xD;
      A few reports in the literature describe treatment successes with a variety of therapeutics;&#xD;
      however, these data are from anecdotal reports or case series and thus provide limited&#xD;
      scientific evidence of effectiveness. Recently published reports as well as personal&#xD;
      observations within our group have suggested that intravenous sodium thiosulfate treatment&#xD;
      may benefit calcinosis patients. In order to gather more robust data on the utility of this&#xD;
      medication in the treatment of calcinosis associated with adult and juvenile dermatomyositis,&#xD;
      we propose to evaluate its effects in the context of a prospective clinical trial.&#xD;
&#xD;
      We plan to enroll participants at a single center into a single-arm, open-label study, with&#xD;
      the overall objective of evaluating the efficacy and safety of intravenous sodium thiosulfate&#xD;
      use in patients with moderate to severe extensive calcinosis associated with juvenile and&#xD;
      adult dermatomyositis.&#xD;
&#xD;
      The study will enroll a maximum of 18 participants over 4 years into the full study, but up&#xD;
      to 250 patients may screen for study entry. Eligible patients will be age 7 or older, and&#xD;
      will have extensive calcinosis (defined as calcinosis involving the torso or 2 extremities)&#xD;
      and moderate to severe calcinosis (indicated by a calcinosis activity visual analogue scale&#xD;
      score of greater than or equal to 3.5 cm out of 10 cm).&#xD;
&#xD;
      Two separate evaluations performed at the NIH prior to initiation of therapy will be used as&#xD;
      baseline data to compare in a pairwise manner to the change in assessments following&#xD;
      treatment with sodium thiosulfate, with all other medications remaining stable. Study&#xD;
      treatment will be 16 g/m2 sodium thiosulfate administered 3 times weekly over a period of 10&#xD;
      weeks at the NIH. Subjects who complete 10 weeks of treatment or reach the primary end point&#xD;
      by week 6 will be considered completers. Following the treatment period, all participants&#xD;
      will return to the NIH for evaluations at weeks 24 and 62.&#xD;
&#xD;
      The primary outcome will be change in calcinosis activity visual analogue scale score from&#xD;
      week 0 to week 10 on therapy, compared to the baseline change in calcinosis activity visual&#xD;
      analogue scale score from week -10 to week 0 pre-treatment. Secondary measures will evaluate&#xD;
      safety and changes in components of the Calcinosis Assessment Tool, clinical assessments of&#xD;
      calcinosis, Mawdsley Calcinosis Questionnaire, quality of life, functional disability, muscle&#xD;
      testing (manual and quantitative), laboratory parameters (muscle enzymes, inflammatory&#xD;
      markers, and endothelial activation markers), gene expression, calcification pathogenesis,&#xD;
      time to improvement, and imaging. Myositis disease activity and damage will also be assessed&#xD;
      by validated measures.&#xD;
&#xD;
      A number of research studies will be incorporated into this clinical trial in an attempt to&#xD;
      understand the immunologic markers associated with calcification in dermatomyositis as well&#xD;
      as the immunologic effects of sodium thiosulfate treatment.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">October 5, 2017</start_date>
  <completion_date type="Anticipated">November 30, 2023</completion_date>
  <primary_completion_date type="Actual">November 4, 2022</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>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in calcinosis severity visual analogue scale score from week 0 to week 10 on therapy, compared to the baseline change in calcinosis severity visual analogue scale score from week -10 to week 0 pre-treatment.</measure>
    <time_frame>Week 6, week 10, week 24, week 62</time_frame>
    <description>Our primary hypothesis is that participants treated with sodium thiosulfate will experience greater improvement in calcinosis activity as assessed by a change in the calcinosis visual analogue scale (VAS) score after treatment, compared with any change in calcinosis activity VAS score during the observation period prior to treatment with sodium thiosulfate.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Validation of the Calcinosis Assessment Tool</measure>
    <time_frame>week -10, Week 6, week 10, week 24, week 62</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence and severity of adverse events, including laboratory abnormalities, over time</measure>
    <time_frame>Week 6, week 10, week 24, week 62</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Improvement of calcinosis lesions, assessed by Calcinosis Assessment Tool, durometry measurements, photography, and imaging studies</measure>
    <time_frame>week -10, Week 6, week 10, week 24, week 62</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Improvement in or stabilization of myositis activity and damage, as assessed by the IMACS core set measures</measure>
    <time_frame>week -10, Week 6, week 10, week 24, week 62</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Greater improvement in quality of life score (CHQ-PF50 for children, SF-36 for adults) from Week 0 to Week 10, compared with any change in quality of life score observed during the pre-treatment period (from Week -10 to Week 0).</measure>
    <time_frame>week -10, Week 6, week 10, week 24, week 62</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in gene expression, measured by RNA and protein analyses (e.g., to evaluate changes due to therapy, or differences between responders and non-responders to therapy)</measure>
    <time_frame>week -10, Week 6, week 10, week 24, week 62</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in functional disability over time, measured by CHAQ/HAQ, CMAS/AMAT/Myositis Functional Index, and physical therapy-related assessments (e.g., range of motion, 6-minute walk, timed up and go, sit to stand, Motor Functional Measure (MFM))</measure>
    <time_frame>week -10, Week 6, week 10, week 24, week 62</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in components of quality of life over time, as measured by quality of life questionnaires (e.g., SF-36, CHQ-PF50, PROMIS, Skindex-29)</measure>
    <time_frame>week -10, Week 6, week 10, week 24, week 62</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in muscle strength over time, measured by manual and quantitative muscle testing</measure>
    <time_frame>week -10, Week 6, week 10, week 24, week 62</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of imaging modalities to assess change in calcinosis (CT, DEXA, MRI, PET)</measure>
    <time_frame>week -10, Week 6, week 10, week 24, week 62</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">14</enrollment>
  <condition>Dermatomyositis</condition>
  <condition>Idiopathic Inflammatory Myopathies</condition>
  <arm_group>
    <arm_group_label>Treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patient will be assessed for 10 weeks off treatment and then will receive 10 weeks of treatment. They will return at weeks 24 and 52 for safety and sustainability of efficacy assessments.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sodium Thiosulfate</intervention_name>
    <description>Sodium thiosulfate is a calcium chelator</description>
    <arm_group_label>Treatment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        -  INCLUSION CRITERIA:&#xD;
&#xD;
               1. At least 7 years of age&#xD;
&#xD;
               2. Meets Bohan and Peter criteria, as modified by the International Myositis&#xD;
                  Assessment and Clinical Studies Group (IMACS), for probable or definite DM or JDM&#xD;
&#xD;
               3. Has extensive calcinosis, defined as calcinosis involving at least 2 extremities&#xD;
                  or the torso&#xD;
&#xD;
               4. Has moderate to severe calcinosis, defined as having a calcinosis activity visual&#xD;
                  analogue scale score of greater than or equal to 3.5 cm out of 10 cm&#xD;
&#xD;
               5. Is willing and able to comply with the requirements of the protocol and to&#xD;
                  undergo all testing&#xD;
&#xD;
               6. Can have IV access established to receive study infusions&#xD;
&#xD;
               7. Myositis disease activity is stable*&#xD;
&#xD;
               8. Medications for myositis are stable for at least 6 weeks prior to study entry**&#xD;
&#xD;
               9. Men and women of reproductive potential must agree to use a reliable form of&#xD;
                  birth control during the 62-week duration of the study&#xD;
&#xD;
              10. Subjects or their legal guardian must sign a written informed consent&#xD;
&#xD;
                    -  Stable myositis disease activity will be defined by physician global and&#xD;
                       patient/parent global VAS that are &lt;4 cm, as well as creatine kinase (CK),&#xD;
                       lactate dehydrogenase (LDH), aldolase, aspartate aminotransferase (AST), and&#xD;
                       alanine aminotransferase (ALT) that are less than or equal to 2X upper limit&#xD;
                       of normal (ULN).&#xD;
&#xD;
                         -  If a patient has a medication for myositis changed in this window for&#xD;
                            reasons besides&#xD;
&#xD;
        their myositis activity and has returned to their baseline medication use prior to&#xD;
&#xD;
        enrollment they will still be eligible.&#xD;
&#xD;
        EXCLUSION CRITERIA:&#xD;
&#xD;
          1. Is pregnant or breastfeeding&#xD;
&#xD;
          2. Has known allergies to sodium thiosulfate, any of its components, or dextrose&#xD;
&#xD;
          3. Has severe myositis disease activity as defined by patient/parent or physician global&#xD;
             activity visual analogue scale score &gt;4 cm out of 10 cm&#xD;
&#xD;
          4. Has had an escalation of immunosuppressive therapy in the 2 months prior to enrollment&#xD;
             for the purpose of treating active myositis disease activity, including the addition&#xD;
             of a new agent to treat the patients underlying disease or an increase in dose of an&#xD;
             existing medication used to treat the patient s disease (other than an adjustment for&#xD;
             weight or body surface area in children)&#xD;
&#xD;
          5. Has a malignancy or had a malignancy within 5 years of diagnosis of their DM (except&#xD;
             for benign skin lesions or basal cell carcinoma)&#xD;
&#xD;
          6. Known or suspected history of alcohol or drug abuse in the 6 months prior to study&#xD;
             enrollment&#xD;
&#xD;
          7. Has systemic lupus erythematosus, scleroderma, or a condition other than DM that is&#xD;
             associated with calcinosis as a complication&#xD;
&#xD;
          8. Has had a change in medications used specifically for calcinosis in the 2 months prior&#xD;
             to enrollment, including but not limited to alendronate, etidronate, pamidronate,&#xD;
             probenecid, colchicine, diltiazem, thalidomide, and aluminum hydroxide&#xD;
&#xD;
          9. Has used probenecid, diltiazem, aluminum hydroxide, or hydrochlorothiazide in the 2&#xD;
             months prior to enrollment&#xD;
&#xD;
         10. Has currently or has a history of any of the following: heart failure, renal&#xD;
             impairment (GFR less than 30 representing severe renal disease), liver disease&#xD;
             (Child-Pugh class C), arrhythmias (that are symptomatic or are concerning for&#xD;
             progression to symptomatic arrhythmias), or recurrent kidney stones (more than one&#xD;
             episode of symptomatic kidney stones separated by at least 1 month), or QT&#xD;
             prolongation, or hypocalcemia, or metabolic acidosis, or hypotension&#xD;
&#xD;
         11. Has severe osteoporosis or has had a bone fracture within a year prior to enrollment.&#xD;
             For adults, severe osteoporosis as defined by the World Health Organization (WHO) as&#xD;
             bone mineral density (BMD) 2.5 standard deviations below that of a young, normal adult&#xD;
             (T-score at or below -2.5 and one or more fractures). For individuals, less than age&#xD;
             18, severe osteoporosis as defined by the First Pediatric Consensus Development&#xD;
             Conference as a Z-score below -2 and one or more fractures.&#xD;
&#xD;
         12. Has a psychiatric illness or medical non-compliance that the study team feels will&#xD;
             make the patient unlikely to complete the study&#xD;
&#xD;
         13. Has dysphagia where non-oral feeding alternatives are needed.&#xD;
&#xD;
         14. Requires supplemental oxygen therapy&#xD;
&#xD;
         15. Has &gt;3 episodes of cellulitis requiring IV antibiotics related to calcinosis within a&#xD;
             year prior to enrollment or cellulitis within 1 month of enrollment&#xD;
&#xD;
         16. Previously received or currently receiving sodium thiosulfate by any route&#xD;
&#xD;
         17. Is on an oral prednisone dose of more than 1mg/kg/day or other oral corticosteroid&#xD;
             equivalent.&#xD;
&#xD;
         18. Is taking any concomitant medications that are thought to alter sodium thiosulfate s&#xD;
             effects or pharmacokinetics. Once patients have met all other inclusion criteria and&#xD;
             no other exclusion criteria this criteria will be checked. A PharmD will evaluate the&#xD;
             patient's current medication list for medications with the potential for interaction&#xD;
             with sodium thiosulfate. Methodology is as follows: He or she will perform a search in&#xD;
             two individual validated medication interaction software programs. He or she will also&#xD;
             perform a literature search via PubMed for case reports of interactions with sodium&#xD;
             thiosulfate. As an additional safeguard, the PharmD will evaluate the medication list&#xD;
             utilizing principles of pharmacology and pharmacokinetics to attempt to identify any&#xD;
             potential interactions not yet documented in the literature.&#xD;
&#xD;
         19. Has any health conditions that, in the opinion of the investigator, significantly&#xD;
             increase the risk of taking sodium thiosulfate or participating in any of the study&#xD;
             procedures&#xD;
&#xD;
         20. Weighs less than 26 kilograms.**&#xD;
&#xD;
         21. Has a regimen of pulse steroids or IVIG that is at an interval besides every 1, 2, or&#xD;
             5 weeks.&#xD;
&#xD;
         22. Has a chronic infection that makes assessment of muscle disease difficult including,&#xD;
             but not limited to, hepatitis, HIV, HTLV 1, and HTLV 2.&#xD;
&#xD;
         23. Has had a severe complication of diabetes in the past year prior to enrollment.&#xD;
&#xD;
         24. Anemia with a HgB less than 10 at time of screening or deemed to be too low to safely&#xD;
             complete study by hematology consult team.&#xD;
&#xD;
               -  We will attempt to enroll patients at a weight greater than 28 kg as these&#xD;
                  patients will be able to obtain all lab work for the study. Patients weighing 26&#xD;
                  to 28 kg will only be able to obtain some of the research blood work. Patients&#xD;
                  less than 26 kg of body weight will be unable to obtain all safety labs, so will&#xD;
                  not be able to enroll.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>7 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Adam I Schiffenbauer, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Institute of Environmental Health Sciences (NIEHS)</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>National Institutes of Health Clinical Center</name>
      <address>
        <city>Bethesda</city>
        <state>Maryland</state>
        <zip>20892</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_2017-E-0161.html</url>
    <description>NIH Clinical Center Detailed Web Page</description>
  </link>
  <verification_date>October 11, 2022</verification_date>
  <study_first_submitted>August 29, 2017</study_first_submitted>
  <study_first_submitted_qc>August 29, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 30, 2017</study_first_posted>
  <last_update_submitted>November 8, 2022</last_update_submitted>
  <last_update_submitted_qc>November 8, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 9, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Calcinosis</keyword>
  <keyword>Dermatomyositis</keyword>
  <keyword>Juvenile Dermatomyositis</keyword>
  <keyword>Idiopathic Inflammatory Myopathies</keyword>
  <keyword>Sodium Thiosulfate</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Muscular Diseases</mesh_term>
    <mesh_term>Dermatomyositis</mesh_term>
    <mesh_term>Myositis</mesh_term>
    <mesh_term>Calcinosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sodium thiosulfate</mesh_term>
  </intervention_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/NCT03267277
org study id: 170161
secondary id: 17-E-0161
nct id: NCT03267277
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
Background:

      Dermatomyositis (DM) and juvenile dermatomyositis (JDM) cause inflammation in the muscles.
      People with DM and JDM can develop calcium deposits in places they should not, known as
      calcinosis. Calcinosis can be painful and cause disabilities and other problems. Researchers
      want to learn more about calcinosis to find treatments for it.

      Objective:

      To test if sodium thiosulfate (STS) can treat people with DM with calcinosis.

      Eligibility:

      People ages 7 and older who have moderate or severe calcinosis. They must have stable DM and
      calcium deposits in the torso or at least 2 limbs.

      Design:

      Participants will be screened with:

        -  Medical history

        -  Physical exam

        -  Muscle strength and function tests

        -  Blood and urine tests

      Participants will have several visits:

        -  7-day pre-treatment visit about 10 weeks before starting STS

        -  Treatment visits over 10 weeks. They will get STS 3 times a week through IV infusion.
           They may be hospitalized the whole time. If they tolerate the drug, they may be
           discharged at certain times. During these times, they will return for the infusions.

        -  3- to 5-day post-treatment visits 24 weeks and 62 weeks after starting STS.

      Visits may include repeats of screening tests and:

        -  Questionnaires

        -  Scans: They lie in a machine that takes pictures of the body. They may be injected with
           a radioactive agent.

        -  Durometry: A small instrument applies pressure on the skin or exposed calcinosis.

        -  Measurements of blood flow in the arms and fingernail blood vessels

        -  Photographs of the skin

        -  Kidney ultrasound

        -  Tests of kidney function

        -  Calcinosis aspiration: A needle placed into areas of calcinosis removes liquid.
Calcinosis, a serious complication of dermatomyositis, involves deposition of calcium
      (carbonate apatite) in soft tissue, and can result in negative impacts on quality of life and
      physical function. To date, there are no known effective therapies that are approved for the
      treatment of dermatomyositis-associated calcinosis, and there is no consensus within the
      medical community on the optimum treatment strategy for this often-debilitating condition.

      A few reports in the literature describe treatment successes with a variety of therapeutics;
      however, these data are from anecdotal reports or case series and thus provide limited
      scientific evidence of effectiveness. Recently published reports as well as personal
      observations within our group have suggested that intravenous sodium thiosulfate treatment
      may benefit calcinosis patients. In order to gather more robust data on the utility of this
      medication in the treatment of calcinosis associated with adult and juvenile dermatomyositis,
      we propose to evaluate its effects in the context of a prospective clinical trial.

      We plan to enroll participants at a single center into a single-arm, open-label study, with
      the overall objective of evaluating the efficacy and safety of intravenous sodium thiosulfate
      use in patients with moderate to severe extensive calcinosis associated with juvenile and
      adult dermatomyositis.

      The study will enroll a maximum of 18 participants over 4 years into the full study, but up
      to 250 patients may screen for study entry. Eligible patients will be age 7 or older, and
      will have extensive calcinosis (defined as calcinosis involving the torso or 2 extremities)
      and moderate to severe calcinosis (indicated by a calcinosis activity visual analogue scale
      score of greater than or equal to 3.5 cm out of 10 cm).

      Two separate evaluations performed at the NIH prior to initiation of therapy will be used as
      baseline data to compare in a pairwise manner to the change in assessments following
      treatment with sodium thiosulfate, with all other medications remaining stable. Study
      treatment will be 16 g/m2 sodium thiosulfate administered 3 times weekly over a period of 10
      weeks at the NIH. Subjects who complete 10 weeks of treatment or reach the primary end point
      by week 6 will be considered completers. Following the treatment period, all participants
      will return to the NIH for evaluations at weeks 24 and 62.

      The primary outcome will be change in calcinosis activity visual analogue scale score from
      week 0 to week 10 on therapy, compared to the baseline change in calcinosis activity visual
      analogue scale score from week -10 to week 0 pre-treatment. Secondary measures will evaluate
      safety and changes in components of the Calcinosis Assessment Tool, clinical assessments of
      calcinosis, Mawdsley Calcinosis Questionnaire, quality of life, functional disability, muscle
      testing (manual and quantitative), laboratory parameters (muscle enzymes, inflammatory
      markers, and endothelial activation markers), gene expression, calcification pathogenesis,
      time to improvement, and imaging. Myositis disease activity and damage will also be assessed
      by validated measures.

      A number of research studies will be incorporated into this clinical trial in an attempt to
      understand the immunologic markers associated with calcification in dermatomyositis as well
      as the immunologic effects of sodium thiosulfate treatment.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Change in calcinosis severity visual analogue scale score from week 0 to week 10 on therapy, compared to the baseline change in calcinosis severity visual analogue scale score from week -10 to week 0 pre-treatment.
time frame: Week 6, week 10, week 24, week 62
description: Our primary hypothesis is that participants treated with sodium thiosulfate will experience greater improvement in calcinosis activity as assessed by a change in the calcinosis visual analogue scale (VAS) score after treatment, compared with any change in calcinosis activity VAS score during the observation period prior to treatment with sodium thiosulfate.
measure: Validation of the Calcinosis Assessment Tool
time frame: week -10, Week 6, week 10, week 24, week 62
measure: Incidence and severity of adverse events, including laboratory abnormalities, over time
time frame: Week 6, week 10, week 24, week 62
measure: Improvement of calcinosis lesions, assessed by Calcinosis Assessment Tool, durometry measurements, photography, and imaging studies
time frame: week -10, Week 6, week 10, week 24, week 62
measure: Improvement in or stabilization of myositis activity and damage, as assessed by the IMACS core set measures
time frame: week -10, Week 6, week 10, week 24, week 62
measure: Greater improvement in quality of life score (CHQ-PF50 for children, SF-36 for adults) from Week 0 to Week 10, compared with any change in quality of life score observed during the pre-treatment period (from Week -10 to Week 0).
time frame: week -10, Week 6, week 10, week 24, week 62
measure: Changes in gene expression, measured by RNA and protein analyses (e.g., to evaluate changes due to therapy, or differences between responders and non-responders to therapy)
time frame: week -10, Week 6, week 10, week 24, week 62
measure: Changes in functional disability over time, measured by CHAQ/HAQ, CMAS/AMAT/Myositis Functional Index, and physical therapy-related assessments (e.g., range of motion, 6-minute walk, timed up and go, sit to stand, Motor Functional Measure (MFM))
time frame: week -10, Week 6, week 10, week 24, week 62
measure: Changes in components of quality of life over time, as measured by quality of life questionnaires (e.g., SF-36, CHQ-PF50, PROMIS, Skindex-29)
time frame: week -10, Week 6, week 10, week 24, week 62
measure: Change in muscle strength over time, measured by manual and quantitative muscle testing
time frame: week -10, Week 6, week 10, week 24, week 62
measure: Assessment of imaging modalities to assess change in calcinosis (CT, DEXA, MRI, PET)
time frame: week -10, Week 6, week 10, week 24, week 62
arm group label: Treatment
arm group type: Experimental
description: Patient will be assessed for 10 weeks off treatment and then will receive 10 weeks of treatment. They will return at weeks 24 and 52 for safety and sustainability of efficacy assessments.
intervention type: Drug
intervention name: Sodium Thiosulfate
description: Sodium thiosulfate is a calcium chelator
arm group label: Treatment
criteria: 
gender: All
minimum age: 7 Years
maximum age: N/A
healthy volunteers: No
last name: Adam I Schiffenbauer, M.D.
role: Principal Investigator
affiliation: National Institute of Environmental Health Sciences (NIEHS)
facility: 
country: United States
url: https://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_2017-E-0161.html
description: NIH Clinical Center Detailed Web Page
responsible party type: Sponsor
mesh term: Muscular Diseases
mesh term: Dermatomyositis
mesh term: Myositis
mesh term: Calcinosis
mesh term: Sodium thiosulfate