<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/NCT03275870</url>
  </required_header>
  <id_info>
    <org_study_id>STUDY19050057</org_study_id>
    <nct_id>NCT03275870</nct_id>
  </id_info>
  <brief_title>Hydroxychloroquine for the Treatment of Hidradenitis Suppurativa</brief_title>
  <official_title>Pilot Study of Hydroxychloroquine for the Treatment of Hidradenitis Suppurativa</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Elena Gonzalez Brant, MD</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Pittsburgh</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Pittsburgh</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Hidradenitis suppurativa (HS) is an under-recognized and debilitating disease. Patients&#xD;
      suffer from recurring painful abscesses and scarring in their armpits, under the breasts,&#xD;
      groin and other areas of the body. The cause of the disease is still unknown and common&#xD;
      treatments are only sometimes effective. Overactivity of the immune system has been&#xD;
      associated with HS and molecules that cause inflammation have been found in the skin from&#xD;
      people with HS. Current therapies have long-term risks including antibiotic resistance and&#xD;
      the investigators aim to find new safe and effective therapies for HS.&#xD;
&#xD;
      Hydroxychloroquine is a medication that has been used safely in other diseases for many&#xD;
      years. The investigators believe that hydroxychloroquine has the potential to improve HS&#xD;
      through multiple mechanisms. Patients enrolled in this study will be treated with&#xD;
      hydroxychloroquine for 6 months. The investigators also aim to look at the blood of patients&#xD;
      with HS to look for inflammatory molecules that we could possibly target for the treatment of&#xD;
      HS. Blood samples will be taken at baseline and following 6 months of treatment.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Hidradenitis suppurativa is a debilitating and mutilating disease and its pathogenesis is&#xD;
      still poorly understood. It involves the development of recurrent, painful nodules in&#xD;
      intertriginous areas that become inflamed, form abscesses that may rupture, and develop&#xD;
      chronic fistula tracts. The cause of hidradenitis suppurativa (HS) is thought to be&#xD;
      multifactorial and may begin with follicular occlusion and rupture, leading to a cascade of&#xD;
      inflammatory responses in susceptible individuals. The disease has been associated with high&#xD;
      body mass index, smoking and genetic predisposition. There is a known association between HS&#xD;
      and the metabolic syndrome, an association that remains after controlling for body mass&#xD;
      index. HS predominantly affects women and ethnic minorities and the prevalence is thought to&#xD;
      be as high as 2%, although embarrassment and lack of awareness may lead to an underestimate&#xD;
      of the true burden of disease.&#xD;
&#xD;
      Although HS is a fairly common disease, relatively little is understood about its&#xD;
      pathogenesis. Immune dysregulation is thought to play a role in disease development.&#xD;
      Increased levels of interleukin (IL)-12, IL-17, IL-23, tumor necrosis factor α, IL-10 and&#xD;
      IL-1β were found to be expressed in lesional skin of HS patients. Recent studies have also&#xD;
      identified elevated levels of IL-17 in the serum of patients with HS.&#xD;
&#xD;
      HS is associated with a significant impact on patient quality of life. Patients suffer from&#xD;
      both the physical and psychological impact of disease. Many therapies have been used to treat&#xD;
      HS, from topical antibiotics to oral retinoids to radical surgeries, but all have limited&#xD;
      efficacy. Despite efforts to control disease, many patients live with chronic wounds and&#xD;
      disability. The decision about appropriate therapy for HS, especially in the early stages, is&#xD;
      mainly based on expert opinion, anecdotal evidence, and small studies. Topical and systemic&#xD;
      antimicrobial treatments are often used as first line therapies, although studies have&#xD;
      repeatedly shown that the abscesses of HS are sterile or contain only normal flora. The&#xD;
      mechanism of improvement with antimicrobials may be through alterations in the local&#xD;
      microbiome. Significant improvement in disease has been seen with dual therapy with twice&#xD;
      daily use of 300mg rifampicin and 300mg clindamycin, neither of which have an FDA indication&#xD;
      for use in HS. Doxycycline is used frequently in HS, but little evidence supports this.&#xD;
      Despite success with the above therapies, the risk of antimicrobial resistance is real, and&#xD;
      is increased with frequent and prolonged use of these medications in HS. Teratogenic effects,&#xD;
      gastrointestinal upset, and photosensitivity with use of tetracyclines, risk for clostridium&#xD;
      difficile colitis with clindamycin, and antimicrobial resistance with rifampicin highlight a&#xD;
      need for safer and effective therapeutic options for the treatment of early HS.&#xD;
&#xD;
      For more advanced disease (Hurley stage II and III), the tumor necrosis factor inhibitor&#xD;
      adalimumab is the only FDA approved biologic treatment for HS. It has shown promise in severe&#xD;
      disease, but only ~50% of patients achieved a clinical response at 12 weeks, and this&#xD;
      clinical response declined over time. Additionally, newer biologic therapies have been used&#xD;
      in small numbers of patients with HS with variable results. Importantly, the cost of these&#xD;
      medications is considerable.&#xD;
&#xD;
      Hydroxychloroquine, initially developed as an antimalarial, has been used successfully for&#xD;
      over 70 years in the treatment of autoimmune disease. Its mechanism of action is still poorly&#xD;
      understood, but it has been shown to have many varied immunomodulatory properties. Evidence&#xD;
      suggests that hydroxychloroquine has an effect on inflammatory disease through decreasing&#xD;
      levels of TNFα and Th-17 cytokines (including IL-6, IL-17, and IL-22). Additionally, studies&#xD;
      have shown a beneficial effect of hydroxychloroquine on lipid metabolism and glucose.&#xD;
      Patients with rheumatoid arthritis (which similarly to HS has an independent association with&#xD;
      cardiovascular disease) who were treated with hydroxychloroquine had an overall decreased&#xD;
      incidence of cardiovascular events. Hydroxychloroquine has a relatively benign safety&#xD;
      profile, with retinopathy being the most concerning long term side effect. The retinopathy&#xD;
      caused by hydroxychloroquine is reversible if identified early, and standard protocols for&#xD;
      the use of this medication include yearly ophthalmologic examination.&#xD;
&#xD;
      Patients with HS suffer daily from the physical and psychological effects of their disease.&#xD;
      Despite insufficient data about disease progression and prognosis, early intervention with&#xD;
      safe and effective therapies is our goal. Hydroxychloroquine has never been used to treat HS,&#xD;
      but the good safety profile, based on many years of usage in other autoimmune diseases, and&#xD;
      known ability to modify many of the aberrant metabolic and inflammatory components of HS make&#xD;
      it an ideal candidate therapy for this debilitating disease.&#xD;
&#xD;
      Research activities:&#xD;
&#xD;
        1. Treatment with hydroxychloroquine 200mg twice daily. Treatment length will be 6 months.&#xD;
           Patients will be allowed to continue or initiate use of topical therapies during the&#xD;
           study.&#xD;
&#xD;
        2. Telephone call to assess toxicity after 1 month of treatment&#xD;
&#xD;
        3. Assessment of hidradenitis suppurativa disease activity using Sartorius scoring at&#xD;
           baseline, and after 3 and 6 months of treatment&#xD;
&#xD;
        4. Collection of patient serum at baseline and after 6 months of treatment&#xD;
&#xD;
        5. Quality of life questionnaire at baseline, 3 and 6 months&#xD;
&#xD;
        6. Follow up telephone call at ~9 and 12 months (3 and 6 months after therapy completion)&#xD;
           to assess for toxicity&#xD;
&#xD;
        7. Baseline ophthalmologic exam for patients on hydroxychloroquine will be conducted within&#xD;
           the first year of treatment&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 28, 2017</start_date>
  <completion_date type="Actual">June 30, 2019</completion_date>
  <primary_completion_date type="Actual">June 30, 2019</primary_completion_date>
  <phase>Phase 1/Phase 2</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 Disease Severity</measure>
    <time_frame>6 months</time_frame>
    <description>Comparison of baseline and post-treatment Sartorius severity scoring Sartorius scoring: minimum 0, no maximum, higher scores mean a worse outcome</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Quality of Life</measure>
    <time_frame>6 months</time_frame>
    <description>Comparison of baseline and post-treatment self-reported quality of life Dermatology Life Quality Index score: minimum 0, maximum 30. higher scores mean worse outcome.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">17</enrollment>
  <condition>Hidradenitis Suppurativa</condition>
  <condition>Hidradenitis</condition>
  <condition>Acne Inversa</condition>
  <condition>Boils</condition>
  <condition>Follicular Occlusion Triad</condition>
  <condition>Follicular Occlusion Tetrad</condition>
  <arm_group>
    <arm_group_label>Hydroxychloroquine treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Hydroxychloroquine 200mg BID for 6 months</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Hydroxychloroquine</intervention_name>
    <description>Treatment of patients with hidradenitis suppurativa with hydroxychloroquine 200mg BID for 6 months</description>
    <arm_group_label>Hydroxychloroquine treatment</arm_group_label>
    <other_name>Plaquenil</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with hidradenitis suppurativa Hurley stage I or II&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Current systemic immunosuppression, current use of biologic medication or use of these&#xD;
             medications in the prior 3 months, patients with known retinal disease, hepatic&#xD;
             disease (HCV, cirrhosis, aspartate aminotransferase or alanine aminotransferase &gt; 2&#xD;
             times the upper limit of normal), psoriasis, porphyria cutanea tarda, platelets &lt;&#xD;
             50,000/ul, leukocytes &lt;4000/ul, or Hb&lt;8g/dl), pregnant patients or women trying to&#xD;
             conceive&#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>Elena M Gonzalez Brant, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Pittsburgh</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Pittsburgh</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15213</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Gonzalez-Lopez MA, Hernandez JL, Lacalle M, Mata C, Lopez-Escobar M, Lopez-Mejias R, Portilla V, Fuentevilla P, Corrales A, Gonzalez-Vela MC, Gonzalez-Gay MA, Blanco R. Increased prevalence of subclinical atherosclerosis in patients with hidradenitis suppurativa (HS). J Am Acad Dermatol. 2016 Aug;75(2):329-35. doi: 10.1016/j.jaad.2016.03.025. Epub 2016 Jun 8.</citation>
    <PMID>27287248</PMID>
  </reference>
  <reference>
    <citation>Nicola WG, Khayria MI, Osfor MM. Plasma testosterone level and the male genital system after chloroquine therapy. Boll Chim Farm. 1997 Jan;136(1):39-43.</citation>
    <PMID>9080720</PMID>
  </reference>
  <reference>
    <citation>Garg A, Lavian J, Lin G, Strunk A, Alloo A. Incidence of hidradenitis suppurativa in the United States: A sex- and age-adjusted population analysis. J Am Acad Dermatol. 2017 Jul;77(1):118-122. doi: 10.1016/j.jaad.2017.02.005. Epub 2017 Mar 9.</citation>
    <PMID>28285782</PMID>
  </reference>
  <reference>
    <citation>Schlapbach C, Hanni T, Yawalkar N, Hunger RE. Expression of the IL-23/Th17 pathway in lesions of hidradenitis suppurativa. J Am Acad Dermatol. 2011 Oct;65(4):790-798. doi: 10.1016/j.jaad.2010.07.010.</citation>
    <PMID>21641076</PMID>
  </reference>
  <reference>
    <citation>van der Zee HH, de Ruiter L, van den Broecke DG, Dik WA, Laman JD, Prens EP. Elevated levels of tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-10 in hidradenitis suppurativa skin: a rationale for targeting TNF-alpha and IL-1beta. Br J Dermatol. 2011 Jun;164(6):1292-8. doi: 10.1111/j.1365-2133.2011.10254.x. Epub 2011 May 17.</citation>
    <PMID>21332464</PMID>
  </reference>
  <reference>
    <citation>Matusiak L, Szczech J, Bieniek A, Nowicka-Suszko D, Szepietowski JC. Increased interleukin (IL)-17 serum levels in patients with hidradenitis suppurativa: Implications for treatment with anti-IL-17 agents. J Am Acad Dermatol. 2017 Apr;76(4):670-675. doi: 10.1016/j.jaad.2016.10.042. Epub 2016 Dec 29.</citation>
    <PMID>28041632</PMID>
  </reference>
  <reference>
    <citation>von der Werth JM, Jemec GB. Morbidity in patients with hidradenitis suppurativa. Br J Dermatol. 2001 Apr;144(4):809-13. doi: 10.1046/j.1365-2133.2001.04137.x.</citation>
    <PMID>11298541</PMID>
  </reference>
  <reference>
    <citation>Andersen RK, Jemec GB. Treatments for hidradenitis suppurativa. Clin Dermatol. 2017 Mar-Apr;35(2):218-224. doi: 10.1016/j.clindermatol.2016.10.018. Epub 2016 Oct 27.</citation>
    <PMID>28274363</PMID>
  </reference>
  <reference>
    <citation>Fischer AH, Haskin A, Okoye GA. Patterns of antimicrobial resistance in lesions of hidradenitis suppurativa. J Am Acad Dermatol. 2017 Feb;76(2):309-313.e2. doi: 10.1016/j.jaad.2016.08.001. Epub 2016 Oct 11.</citation>
    <PMID>27742173</PMID>
  </reference>
  <reference>
    <citation>Kimball AB, Okun MM, Williams DA, Gottlieb AB, Papp KA, Zouboulis CC, Armstrong AW, Kerdel F, Gold MH, Forman SB, Korman NJ, Giamarellos-Bourboulis EJ, Crowley JJ, Lynde C, Reguiai Z, Prens EP, Alwawi E, Mostafa NM, Pinsky B, Sundaram M, Gu Y, Carlson DM, Jemec GB. Two Phase 3 Trials of Adalimumab for Hidradenitis Suppurativa. N Engl J Med. 2016 Aug 4;375(5):422-34. doi: 10.1056/NEJMoa1504370.</citation>
    <PMID>27518661</PMID>
  </reference>
  <reference>
    <citation>Rainsford KD, Parke AL, Clifford-Rashotte M, Kean WF. Therapy and pharmacological properties of hydroxychloroquine and chloroquine in treatment of systemic lupus erythematosus, rheumatoid arthritis and related diseases. Inflammopharmacology. 2015 Oct;23(5):231-69. doi: 10.1007/s10787-015-0239-y. Epub 2015 Aug 6.</citation>
    <PMID>26246395</PMID>
  </reference>
  <reference>
    <citation>van den Borne BE, Dijkmans BA, de Rooij HH, le Cessie S, Verweij CL. Chloroquine and hydroxychloroquine equally affect tumor necrosis factor-alpha, interleukin 6, and interferon-gamma production by peripheral blood mononuclear cells. J Rheumatol. 1997 Jan;24(1):55-60.</citation>
    <PMID>9002011</PMID>
  </reference>
  <reference>
    <citation>Silva JC, Mariz HA, Rocha LF Jr, Oliveira PS, Dantas AT, Duarte AL, Pitta Ida R, Galdino SL, Pitta MG. Hydroxychloroquine decreases Th17-related cytokines in systemic lupus erythematosus and rheumatoid arthritis patients. Clinics (Sao Paulo). 2013 Jun;68(6):766-71. doi: 10.6061/clinics/2013(06)07.</citation>
    <PMID>23778483</PMID>
  </reference>
  <reference>
    <citation>Hage MP, Al-Badri MR, Azar ST. A favorable effect of hydroxychloroquine on glucose and lipid metabolism beyond its anti-inflammatory role. Ther Adv Endocrinol Metab. 2014 Aug;5(4):77-85. doi: 10.1177/2042018814547204.</citation>
    <PMID>25343023</PMID>
  </reference>
  <reference>
    <citation>Sharma TS, Wasko MC, Tang X, Vedamurthy D, Yan X, Cote J, Bili A. Hydroxychloroquine Use Is Associated With Decreased Incident Cardiovascular Events in Rheumatoid Arthritis Patients. J Am Heart Assoc. 2016 Jan 4;5(1):e002867. doi: 10.1161/JAHA.115.002867.</citation>
    <PMID>26727968</PMID>
  </reference>
  <verification_date>March 2020</verification_date>
  <study_first_submitted>August 31, 2017</study_first_submitted>
  <study_first_submitted_qc>September 5, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 8, 2017</study_first_posted>
  <results_first_submitted>January 23, 2020</results_first_submitted>
  <results_first_submitted_qc>March 9, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">March 24, 2020</results_first_posted>
  <last_update_submitted>March 23, 2020</last_update_submitted>
  <last_update_submitted_qc>March 23, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">April 2, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of Pittsburgh</investigator_affiliation>
    <investigator_full_name>Elena Gonzalez Brant, MD</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hidradenitis Suppurativa</mesh_term>
    <mesh_term>Hidradenitis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hydroxychloroquine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>June 3, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/70/NCT03275870/ICF_002.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>June 3, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/70/NCT03275870/Prot_SAP_003.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Hydroxychloroquine Treatment</title>
          <description>Hydroxychloroquine 200mg BID for 6 months&#xD;
Hydroxychloroquine: Treatment of patients with hidradenitis suppurativa with hydroxychloroquine 200mg BID for 6 months</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="17"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Hydroxychloroquine Treatment</title>
          <description>Hydroxychloroquine 200mg BID for 6 months&#xD;
Hydroxychloroquine: Treatment of patients with hidradenitis suppurativa with hydroxychloroquine 200mg BID for 6 months</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="17"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="38.9" lower_limit="19" upper_limit="64"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Caucasian</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Black</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in Disease Severity</title>
        <description>Comparison of baseline and post-treatment Sartorius severity scoring Sartorius scoring: minimum 0, no maximum, higher scores mean a worse outcome</description>
        <time_frame>6 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Hydroxychloroquine Treatment</title>
            <description>Hydroxychloroquine 200mg BID for 6 months&#xD;
Hydroxychloroquine: Treatment of patients with hidradenitis suppurativa with hydroxychloroquine 200mg BID for 6 months</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Disease Severity</title>
          <description>Comparison of baseline and post-treatment Sartorius severity scoring Sartorius scoring: minimum 0, no maximum, higher scores mean a worse outcome</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline sartorius score</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23.3" spread="16.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>6 month sartorius score</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17.7" spread="14.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.042</p_value>
            <p_value_desc>p value &lt;0.05 used as threshold for significance</p_value_desc>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Quality of Life</title>
        <description>Comparison of baseline and post-treatment self-reported quality of life Dermatology Life Quality Index score: minimum 0, maximum 30. higher scores mean worse outcome.</description>
        <time_frame>6 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Hydroxychloroquine Treatment</title>
            <description>Hydroxychloroquine 200mg BID for 6 months&#xD;
Hydroxychloroquine: Treatment of patients with hidradenitis suppurativa with hydroxychloroquine 200mg BID for 6 months</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Quality of Life</title>
          <description>Comparison of baseline and post-treatment self-reported quality of life Dermatology Life Quality Index score: minimum 0, maximum 30. higher scores mean worse outcome.</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline DLQI score</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14.7" spread="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>6 month DLQI score</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6" spread="7.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.213</p_value>
            <p_value_desc>P value of &lt;0.05 used as threshold for significance</p_value_desc>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>13 months</time_frame>
      <desc>Patients were periodically asked about side effects by a telephone call 1 month after starting treatment, at the 3 and 6 month follow up visit.&#xD;
They were evaluated for blurred vision, changes in vision, diarrhea, nausea, vomiting, headache, pruritus, anorexia and abdominal pain</desc>
      <group_list>
        <group group_id="E1">
          <title>Hydroxychloroquine Treatment</title>
          <description>Hydroxychloroquine 200mg BID for 6 months&#xD;
Hydroxychloroquine: Treatment of patients with hidradenitis suppurativa with hydroxychloroquine 200mg BID for 6 months</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>blurred vision</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>headache</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>urticaria</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>We did not reach the target number of participants needed to achieve target power and statistically reliable results leading to unreliable or uninterpretable data.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Dr. Elena Gonzalez Brant, PI</name_or_title>
      <organization>Beth Israel Lahey Health</organization>
      <phone>6173191221</phone>
      <email>emgbrant@gmail.com</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03275870
org study id: STUDY19050057
nct id: NCT03275870
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
Hidradenitis suppurativa (HS) is an under-recognized and debilitating disease. Patients
      suffer from recurring painful abscesses and scarring in their armpits, under the breasts,
      groin and other areas of the body. The cause of the disease is still unknown and common
      treatments are only sometimes effective. Overactivity of the immune system has been
      associated with HS and molecules that cause inflammation have been found in the skin from
      people with HS. Current therapies have long-term risks including antibiotic resistance and
      the investigators aim to find new safe and effective therapies for HS.

      Hydroxychloroquine is a medication that has been used safely in other diseases for many
      years. The investigators believe that hydroxychloroquine has the potential to improve HS
      through multiple mechanisms. Patients enrolled in this study will be treated with
      hydroxychloroquine for 6 months. The investigators also aim to look at the blood of patients
      with HS to look for inflammatory molecules that we could possibly target for the treatment of
      HS. Blood samples will be taken at baseline and following 6 months of treatment.
Hidradenitis suppurativa is a debilitating and mutilating disease and its pathogenesis is
      still poorly understood. It involves the development of recurrent, painful nodules in
      intertriginous areas that become inflamed, form abscesses that may rupture, and develop
      chronic fistula tracts. The cause of hidradenitis suppurativa (HS) is thought to be
      multifactorial and may begin with follicular occlusion and rupture, leading to a cascade of
      inflammatory responses in susceptible individuals. The disease has been associated with high
      body mass index, smoking and genetic predisposition. There is a known association between HS
      and the metabolic syndrome, an association that remains after controlling for body mass
      index. HS predominantly affects women and ethnic minorities and the prevalence is thought to
      be as high as 2%, although embarrassment and lack of awareness may lead to an underestimate
      of the true burden of disease.

      Although HS is a fairly common disease, relatively little is understood about its
      pathogenesis. Immune dysregulation is thought to play a role in disease development.
      Increased levels of interleukin (IL)-12, IL-17, IL-23, tumor necrosis factor α, IL-10 and
      IL-1β were found to be expressed in lesional skin of HS patients. Recent studies have also
      identified elevated levels of IL-17 in the serum of patients with HS.

      HS is associated with a significant impact on patient quality of life. Patients suffer from
      both the physical and psychological impact of disease. Many therapies have been used to treat
      HS, from topical antibiotics to oral retinoids to radical surgeries, but all have limited
      efficacy. Despite efforts to control disease, many patients live with chronic wounds and
      disability. The decision about appropriate therapy for HS, especially in the early stages, is
      mainly based on expert opinion, anecdotal evidence, and small studies. Topical and systemic
      antimicrobial treatments are often used as first line therapies, although studies have
      repeatedly shown that the abscesses of HS are sterile or contain only normal flora. The
      mechanism of improvement with antimicrobials may be through alterations in the local
      microbiome. Significant improvement in disease has been seen with dual therapy with twice
      daily use of 300mg rifampicin and 300mg clindamycin, neither of which have an FDA indication
      for use in HS. Doxycycline is used frequently in HS, but little evidence supports this.
      Despite success with the above therapies, the risk of antimicrobial resistance is real, and
      is increased with frequent and prolonged use of these medications in HS. Teratogenic effects,
      gastrointestinal upset, and photosensitivity with use of tetracyclines, risk for clostridium
      difficile colitis with clindamycin, and antimicrobial resistance with rifampicin highlight a
      need for safer and effective therapeutic options for the treatment of early HS.

      For more advanced disease (Hurley stage II and III), the tumor necrosis factor inhibitor
      adalimumab is the only FDA approved biologic treatment for HS. It has shown promise in severe
      disease, but only ~50% of patients achieved a clinical response at 12 weeks, and this
      clinical response declined over time. Additionally, newer biologic therapies have been used
      in small numbers of patients with HS with variable results. Importantly, the cost of these
      medications is considerable.

      Hydroxychloroquine, initially developed as an antimalarial, has been used successfully for
      over 70 years in the treatment of autoimmune disease. Its mechanism of action is still poorly
      understood, but it has been shown to have many varied immunomodulatory properties. Evidence
      suggests that hydroxychloroquine has an effect on inflammatory disease through decreasing
      levels of TNFα and Th-17 cytokines (including IL-6, IL-17, and IL-22). Additionally, studies
      have shown a beneficial effect of hydroxychloroquine on lipid metabolism and glucose.
      Patients with rheumatoid arthritis (which similarly to HS has an independent association with
      cardiovascular disease) who were treated with hydroxychloroquine had an overall decreased
      incidence of cardiovascular events. Hydroxychloroquine has a relatively benign safety
      profile, with retinopathy being the most concerning long term side effect. The retinopathy
      caused by hydroxychloroquine is reversible if identified early, and standard protocols for
      the use of this medication include yearly ophthalmologic examination.

      Patients with HS suffer daily from the physical and psychological effects of their disease.
      Despite insufficient data about disease progression and prognosis, early intervention with
      safe and effective therapies is our goal. Hydroxychloroquine has never been used to treat HS,
      but the good safety profile, based on many years of usage in other autoimmune diseases, and
      known ability to modify many of the aberrant metabolic and inflammatory components of HS make
      it an ideal candidate therapy for this debilitating disease.

      Research activities:

        1. Treatment with hydroxychloroquine 200mg twice daily. Treatment length will be 6 months.
           Patients will be allowed to continue or initiate use of topical therapies during the
           study.

        2. Telephone call to assess toxicity after 1 month of treatment

        3. Assessment of hidradenitis suppurativa disease activity using Sartorius scoring at
           baseline, and after 3 and 6 months of treatment

        4. Collection of patient serum at baseline and after 6 months of treatment

        5. Quality of life questionnaire at baseline, 3 and 6 months

        6. Follow up telephone call at ~9 and 12 months (3 and 6 months after therapy completion)
           to assess for toxicity

        7. Baseline ophthalmologic exam for patients on hydroxychloroquine will be conducted within
           the first year of treatment
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Change in Disease Severity
time frame: 6 months
description: Comparison of baseline and post-treatment Sartorius severity scoring Sartorius scoring: minimum 0, no maximum, higher scores mean a worse outcome
measure: Change in Quality of Life
time frame: 6 months
description: Comparison of baseline and post-treatment self-reported quality of life Dermatology Life Quality Index score: minimum 0, maximum 30. higher scores mean worse outcome.
arm group label: Hydroxychloroquine treatment
arm group type: Experimental
description: Hydroxychloroquine 200mg BID for 6 months
intervention type: Drug
intervention name: Hydroxychloroquine
description: Treatment of patients with hidradenitis suppurativa with hydroxychloroquine 200mg BID for 6 months
arm group label: Hydroxychloroquine treatment
other name: Plaquenil
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Elena M Gonzalez Brant, MD
role: Principal Investigator
affiliation: University of Pittsburgh
facility: 
country: United States
citation: Gonzalez-Lopez MA, Hernandez JL, Lacalle M, Mata C, Lopez-Escobar M, Lopez-Mejias R, Portilla V, Fuentevilla P, Corrales A, Gonzalez-Vela MC, Gonzalez-Gay MA, Blanco R. Increased prevalence of subclinical atherosclerosis in patients with hidradenitis suppurativa (HS). J Am Acad Dermatol. 2016 Aug;75(2):329-35. doi: 10.1016/j.jaad.2016.03.025. Epub 2016 Jun 8.
PMID: 27287248
citation: Nicola WG, Khayria MI, Osfor MM. Plasma testosterone level and the male genital system after chloroquine therapy. Boll Chim Farm. 1997 Jan;136(1):39-43.
PMID: 9080720
citation: Garg A, Lavian J, Lin G, Strunk A, Alloo A. Incidence of hidradenitis suppurativa in the United States: A sex- and age-adjusted population analysis. J Am Acad Dermatol. 2017 Jul;77(1):118-122. doi: 10.1016/j.jaad.2017.02.005. Epub 2017 Mar 9.
PMID: 28285782
citation: Schlapbach C, Hanni T, Yawalkar N, Hunger RE. Expression of the IL-23/Th17 pathway in lesions of hidradenitis suppurativa. J Am Acad Dermatol. 2011 Oct;65(4):790-798. doi: 10.1016/j.jaad.2010.07.010.
PMID: 21641076
citation: van der Zee HH, de Ruiter L, van den Broecke DG, Dik WA, Laman JD, Prens EP. Elevated levels of tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-10 in hidradenitis suppurativa skin: a rationale for targeting TNF-alpha and IL-1beta. Br J Dermatol. 2011 Jun;164(6):1292-8. doi: 10.1111/j.1365-2133.2011.10254.x. Epub 2011 May 17.
PMID: 21332464
citation: Matusiak L, Szczech J, Bieniek A, Nowicka-Suszko D, Szepietowski JC. Increased interleukin (IL)-17 serum levels in patients with hidradenitis suppurativa: Implications for treatment with anti-IL-17 agents. J Am Acad Dermatol. 2017 Apr;76(4):670-675. doi: 10.1016/j.jaad.2016.10.042. Epub 2016 Dec 29.
PMID: 28041632
citation: von der Werth JM, Jemec GB. Morbidity in patients with hidradenitis suppurativa. Br J Dermatol. 2001 Apr;144(4):809-13. doi: 10.1046/j.1365-2133.2001.04137.x.
PMID: 11298541
citation: Andersen RK, Jemec GB. Treatments for hidradenitis suppurativa. Clin Dermatol. 2017 Mar-Apr;35(2):218-224. doi: 10.1016/j.clindermatol.2016.10.018. Epub 2016 Oct 27.
PMID: 28274363
citation: Fischer AH, Haskin A, Okoye GA. Patterns of antimicrobial resistance in lesions of hidradenitis suppurativa. J Am Acad Dermatol. 2017 Feb;76(2):309-313.e2. doi: 10.1016/j.jaad.2016.08.001. Epub 2016 Oct 11.
PMID: 27742173
citation: Kimball AB, Okun MM, Williams DA, Gottlieb AB, Papp KA, Zouboulis CC, Armstrong AW, Kerdel F, Gold MH, Forman SB, Korman NJ, Giamarellos-Bourboulis EJ, Crowley JJ, Lynde C, Reguiai Z, Prens EP, Alwawi E, Mostafa NM, Pinsky B, Sundaram M, Gu Y, Carlson DM, Jemec GB. Two Phase 3 Trials of Adalimumab for Hidradenitis Suppurativa. N Engl J Med. 2016 Aug 4;375(5):422-34. doi: 10.1056/NEJMoa1504370.
PMID: 27518661
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PMID: 26246395
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PMID: 26727968
responsible party type: Sponsor-Investigator
investigator affiliation: University of Pittsburgh
investigator full name: Elena Gonzalez Brant, MD
investigator title: Principal Investigator
mesh term: Hidradenitis Suppurativa
mesh term: Hidradenitis
mesh term: Hydroxychloroquine
sharing ipd: Undecided
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: We did not reach the target number of participants needed to achieve target power and statistically reliable results leading to unreliable or uninterpretable data.
point of contact: 