<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/NCT03042637</url>
  </required_header>
  <id_info>
    <org_study_id>12345</org_study_id>
    <nct_id>NCT03042637</nct_id>
  </id_info>
  <brief_title>Safety and Efficacy of Combination Acthar Gel and Tacrolimus in the Treatment of Steroid Resistant Nephrotic Syndrome</brief_title>
  <official_title>Safety and Efficacy of Combination Acthar Gel and Tacrolimus in the Treatment of Steroid Resistant Nephrotic Syndrome</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Southeast Renal Research Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Southeast Renal Research Institute</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The management of steroid-resistant nephrotic syndrome (SRNS) remains a persistent problem&#xD;
      for investigators in part because of the wide array of pathogenic cccccccccc mechanisms that&#xD;
      contribute to these disorders as well as the lack ofs. While glucocorticoids remain the&#xD;
      primary therapy for many forms of protein uric glomerularxxxxxxxxx diseases, prolonged use is&#xD;
      associated with significant morbidities including steroid induced diabetes, metabolic bone&#xD;
      disease, and excessive weight gain.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Multiple agents have been investigated in the treatment of patients with SRNS, but there is&#xD;
      no consensus on what constitutes optimal therapy. Previous studiesoids and have shown&#xD;
      complete and partial response rates between 40% and 60%. More recently, calcineurin&#xD;
      inhibitors (CNI) have become an effective second line therapy with similar response rates&#xD;
      between 50%-70%. However, both treatment regiments are limited by the risk for infection as&#xD;
      well as the development of vvvvvvv CNI-induced nephrotoxicity and progressive renal disease.&#xD;
      Acthar gel is a porcine pituitary preparation composed of ACTH and for treatment of&#xD;
      idiopathic nephrotic syndrome. Previous studies, as well as more current studies, have shown&#xD;
      that ACTHar gel can effectively reduce proteinuriammmmmmmm in idiopathic membranous&#xD;
      glomerulonephritis and other forms of glomerulopathy including focal segmental&#xD;
      glomerulosclerosis (FSGS) and advanced diabetic nephropathy. While the mechanism is unknown,&#xD;
      previous studies have shown that melanocortin 1-receptors are expressed in glomerular&#xD;
      podocytes and thatpathway could be involved in the protein lowering effects of ACTHar&#xD;
      bbbbbbbbgel. Incubation of cultured podocytes with ACTH leads to activation of MCR-1&#xD;
      receptors and the subsequent stimulation of protein kinase A (PKA) through a&#xD;
      G-protein-dependent pathway. The downstream phosphorylation and stabilization of Rho GTPases,&#xD;
      synaptopodin and other cell-cytoskeletal associated proteins may stabilize podocyte function&#xD;
      and density.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Suspended</overall_status>
  <why_stopped>
    Bb&#xD;
  </why_stopped>
  <start_date type="Actual">January 2012</start_date>
  <completion_date type="Anticipated">December 2021</completion_date>
  <primary_completion_date type="Actual">December 2016</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Only</observational_model>
    <time_perspective>Cross-Sectional</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Reduction of proteinuria in idiopathic membranous glomerulonephritis (MGN) and other forms of glomerulopathy including focal segmental glomerulosclerosis (FSGS) and advanced diabetic nephropathy</measure>
    <time_frame>6 months</time_frame>
    <description>Subjects with steroid resistant nephrotic syndrome were treated with sub-cutaneous (SQ) ACTHar gel, (40-80 units) SQ 2X-3X/week. After 6 months of ACTHar gel therapy subjects achieving complete remission were weaned off therapy over a 3-12 month period.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Partial remission or no response to treatment regiment</measure>
    <time_frame>6 months</time_frame>
    <description>Subjects exhibiting no response or partial remission were maintained on existing ACTHar gel doses and started on oral Tacrolimus (0.03 to 0.06 mg/kg/day) titrating to a trough level of 5-10 ng/ml for an additional 6 months.</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <condition>Nephrotic Syndrome</condition>
  <arm_group>
    <arm_group_label>Acthar Gel and Tacrolimus</arm_group_label>
    <description>Combination therapy with Acthar Gel and Tacrolimus</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Acthar Gel and Tacrolimus</intervention_name>
    <description>Combination therapy with Acthar Gel and Tacrolimus (0.5-3.0 mg BID) following 6 months of ACTH therapy only</description>
    <arm_group_label>Acthar Gel and Tacrolimus</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        patients between the ages of 18 and 80 with refractory nephrotic syndrome secondary to Type&#xD;
        I or Type II diabetes&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  refractory nephrotic syndrome secondary, defined as subjects having a urine protein/Cr&#xD;
             ratio over 3.0 while actively receiving ACE inhibitors and hyperglycemic therapy&#xD;
             (i.e., insulin or oral hyperglycemic agents).&#xD;
&#xD;
          -  Type I or Type II diabetes&#xD;
&#xD;
          -  receiving combination therapy with an ACE inhibitor and a second protein lowering&#xD;
             agent (e.g., ARB, non dihydropyridine CCB, or spironolactone).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  known primary or secondary membranous glomerulonephritis (GN)&#xD;
&#xD;
          -  primary or secondary focal segmental glomerulosclerosis&#xD;
&#xD;
          -  other nondiabetic forms of glomerulopathy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>James A Tumlin, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>NephroNet Clinical Research Consortium</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Nephronet</name>
      <address>
        <city>Chattanooga</city>
        <state>Tennessee</state>
        <zip>37408</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2021</verification_date>
  <study_first_submitted>March 30, 2016</study_first_submitted>
  <study_first_submitted_qc>February 1, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">February 3, 2017</study_first_posted>
  <last_update_submitted>February 15, 2021</last_update_submitted>
  <last_update_submitted_qc>February 15, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">February 17, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Southeast Renal Research Institute</investigator_affiliation>
    <investigator_full_name>James A. Tumlin 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>Nephrotic Syndrome</mesh_term>
    <mesh_term>Nephrosis</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tacrolimus</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03042637
org study id: 12345
nct id: NCT03042637
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The management of steroid-resistant nephrotic syndrome (SRNS) remains a persistent problem
      for investigators in part because of the wide array of pathogenic cccccccccc mechanisms that
      contribute to these disorders as well as the lack ofs. While glucocorticoids remain the
      primary therapy for many forms of protein uric glomerularxxxxxxxxx diseases, prolonged use is
      associated with significant morbidities including steroid induced diabetes, metabolic bone
      disease, and excessive weight gain.
Multiple agents have been investigated in the treatment of patients with SRNS, but there is
      no consensus on what constitutes optimal therapy. Previous studiesoids and have shown
      complete and partial response rates between 40% and 60%. More recently, calcineurin
      inhibitors (CNI) have become an effective second line therapy with similar response rates
      between 50%-70%. However, both treatment regiments are limited by the risk for infection as
      well as the development of vvvvvvv CNI-induced nephrotoxicity and progressive renal disease.
      Acthar gel is a porcine pituitary preparation composed of ACTH and for treatment of
      idiopathic nephrotic syndrome. Previous studies, as well as more current studies, have shown
      that ACTHar gel can effectively reduce proteinuriammmmmmmm in idiopathic membranous
      glomerulonephritis and other forms of glomerulopathy including focal segmental
      glomerulosclerosis (FSGS) and advanced diabetic nephropathy. While the mechanism is unknown,
      previous studies have shown that melanocortin 1-receptors are expressed in glomerular
      podocytes and thatpathway could be involved in the protein lowering effects of ACTHar
      bbbbbbbbgel. Incubation of cultured podocytes with ACTH leads to activation of MCR-1
      receptors and the subsequent stimulation of protein kinase A (PKA) through a
      G-protein-dependent pathway. The downstream phosphorylation and stabilization of Rho GTPases,
      synaptopodin and other cell-cytoskeletal associated proteins may stabilize podocyte function
      and density.
observational model: Case-Only
time perspective: Cross-Sectional
measure: Reduction of proteinuria in idiopathic membranous glomerulonephritis (MGN) and other forms of glomerulopathy including focal segmental glomerulosclerosis (FSGS) and advanced diabetic nephropathy
time frame: 6 months
description: Subjects with steroid resistant nephrotic syndrome were treated with sub-cutaneous (SQ) ACTHar gel, (40-80 units) SQ 2X-3X/week. After 6 months of ACTHar gel therapy subjects achieving complete remission were weaned off therapy over a 3-12 month period.
measure: Partial remission or no response to treatment regiment
time frame: 6 months
description: Subjects exhibiting no response or partial remission were maintained on existing ACTHar gel doses and started on oral Tacrolimus (0.03 to 0.06 mg/kg/day) titrating to a trough level of 5-10 ng/ml for an additional 6 months.
arm group label: Acthar Gel and Tacrolimus
description: Combination therapy with Acthar Gel and Tacrolimus
intervention type: Drug
intervention name: Acthar Gel and Tacrolimus
description: Combination therapy with Acthar Gel and Tacrolimus (0.5-3.0 mg BID) following 6 months of ACTH therapy only
arm group label: Acthar Gel and Tacrolimus
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: James A Tumlin, MD
role: Principal Investigator
affiliation: NephroNet Clinical Research Consortium
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Southeast Renal Research Institute
investigator full name: James A. Tumlin MD
investigator title: Principal Investigator
mesh term: Nephrotic Syndrome
mesh term: Nephrosis
mesh term: Syndrome
mesh term: Tacrolimus
sharing ipd: No