Idiopathic Focal Segmental Glomerulosclerosis (FSGS) and Treatment With ACTH
Condition: Kidney Diseases
MeSH terms: Kidney Diseases; Glomerulosclerosis, Focal Segmental
Study type: Interventional
Phase: Phase 4

Summary: 
      FSGS is an immunologic disorder wherein circulating immune proteins cause damage to the
      kidneys and progressive injury and scarring. Corticosteroid therapy is occasionally, but not
      nearly universally, successful in reducing proteinuria, and when patients respond, they have
      a favorable prognosis. The investigators believe that ACTH therapy (H.P. Acthar Gel) can
      provide a more rapid, well tolerated reduction in glomerular injury.
    

Detailed description: 
      EXPERIMENTAL TREATMENT: Patients with biopsy proven FSGS will be treated with ACTH in an
      open-label pilot study of tolerability and efficacy. The investigators will recruit 18-20
      patients to complete this study, over 2 years.

      ACTH therapy: Patients will receive H.P. Acthar gel IM or SQ, initially at 40 IU SQ every
      week for 16 weeks of therapy. All patients will be treated to goal BP of <140/90mmHg with all
      patients treated with ACEi or ARB therapy as tolerated. H2 receptor blockade or proton pump
      inhibitor therapy will also be offered all patients. Dose will be titrated up to 160 IU SQ
      every week, if at 1 month the patient has had no substantial reduction in proteinuria, no
      deterioration of blood pressure and no development of hyperglycemia as well as no serious
      adverse events felt to be related to the medication.

      CLINICAL OUTCOME: Patients will be followed for the primary outcome of remission of
      proteinuria. This will be defined as partial remission when the proteinuria is reduced below
      50% of the initial, pre treatment value and as complete remission when the proteinuria is
      reduced to < 0.5 g/g or <500 mg/day on a 24 hour urine sample. Secondary outcomes will
      include effects on eGFR, effects on glucose levels, effects on blood pressure (total doses of
      antihypertensive medications and absolute changes in blood pressure) and on immune status.
      Outcomes will be determined by looking at 3 month and 6 month values of urine protein and
      eGFR following initiation of treatment.

      IMMUNOLOGIC TESTING: In order to further assess the role of immunologic perturations on FSGS
      and the effect of ACTH on the immune system, all patients will bank blood and urine before
      the start of the study for cytokine analysis, RNA, DNA, protein and protoarray testing.

      MONITORING AND SAFETY: All patients will undergo full informed consent per the Stanford
      Institutional Review Board. Contact numbers will be provided and study staff will be
      available at all times in case of any medical emergencies. All patients will continue with
      routine health monitoring with a minimal of monthly assessments. A comprehensive interview
      will be undertaken to assess for side effects, complete physical exams will be accomplished
      including vital signs, CBC, clinical chemistries (including electrolytes, creatinine, glucose
      and liver function tests), urine for protein and creatinine and fasting lipid profiles every
      3 months. Also at screening and baseline.

      PATIENT WITHDRAWAL/TERMINATION OF STUDY: Patients will be closely monitored, as detailed
      above. Patients may voluntarily leave the study at any time, although every effort will be
      made to follow their clinical course and monitor for safety issues and possible benefits of
      therapy. Patient will be monitored for adverse events. Patients with severe adverse events
      will be evaluated for the relatedness of their event to the study medication. If the event is
      considered severe and possibly or probably related to the study medication, the medication
      will be discontinued and the patient will continue to be monitored. In the case the adverse
      event is possibly related, the medication may be restarted, if the investigator and subject
      agree. For patients with probably related severe adverse events, study treatment will be
      discontinued however, the investigators will still follow the patient to see if the course of
      their underlying disease was modified by treatment. As this is an open label, pilot study, no
      data safety monitoring board is felt to be necessary. If drug related SAEs develop in more
      than 20% of patients, the study will be submitted back to the IRB to determine if it should
      continue.
    

Intervention name(s): H.P. Acthar Gel
Intervention type(s): Drug
Intervention description(s): Patients were treated with 40 units subcutaneously (SC) weekly for 2 weeks, then dose increased to 80 units SC weekly for 2 weeks followed by 80 units SC twice weekly to complete 16 weeks of therapy.
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment