Adrenocorticotropic Hormone (ACTH) for Frequently Relapsing and Steroid Dependent Nephrotic Syndrome
Condition: Nephrotic Syndrome
MeSH terms: Nephrotic Syndrome; Nephrosis; Syndrome
Intervention: ACTH
Intervention description: Patients will receive ACTH twice weekly for 6 months, with a 50% dose reduction allowed for side effects. The dose will be reduce by 50% at 6 months and continued for an additional 6 months.
Intervention MeSH terms: Adrenocorticotropic Hormone; Melanocyte-Stimulating Hormones; beta-Endorphin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 31.0
Sex: All
Minimum age: 2 Years
Maximum age: 20 Years
Healthy volunteers: No

Summary:

      In childhood nephrotic syndrome, the kidneys leak protein, causing body swelling and a
      variety of possible complications such as infection, blood clots, and kidney failure. The
      first-line treatment for nephrotic syndrome is corticosteroids. Many children respond to
      prednisone treatment, but the disease comes back (relapses) when the prednisone is stopped or
      the dose is reduced. Children with frequently relapsing or steroid dependent nephrotic
      syndrome are at risk for toxicity from frequent exposure to corticosteroids.

      Currently, the standard treatment for frequently relapsing and steroid dependent nephrotic
      syndrome involves a variety of medications that suppress the immune system, which can produce
      serious side effects. We propose a study to examine the effects of a different medication,
      ACTH, on nephrotic syndrome. ACTH is a hormone naturally found in the body. Recently, in
      adult studies, ACTH has been shown to be effective for the treatment of nephrotic syndrome.
      It has also been shown to have mild and reversible side effects. ACTH is potentially an
      attractive therapeutic alternative for the treatment of frequently relapsing and steroid
      dependent nephrotic syndrome in children. Our study will randomly assign patients with
      frequently relapsing or steroid dependent nephrotic syndrome to either ACTH treatment or no
      treatment. This will allow us to study the effects of ACTH on this disease and its side
      effects, by comparing how patients do on ACTH treatment versus no treatment. We hypothesize
      that ACTH gel is superior to no treatment in maintaining remission in children with
      frequently relapsing or steroid dependent nephrotic syndrome.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Age >1 year at onset of nephrotic syndrome

          2. Age 2-20 years at time of randomization

          3. Estimated glomerular filtration rate (GFR) > 50 ml/min/1.73 m2 at most recent measure
             prior to randomization (Schwartz formula)

          4. Steroid responsive nephrotic syndrome throughout clinical course (never required a
             second agent to attain remission of a relapse of nephrotic syndrome)

          5. History of frequently relapsing or steroid dependent nephrotic syndrome (defined as 2
             or more relapses within 6 months after initial therapy or 4 or more relapses in any 12
             month period OR relapse during taper or within 2 weeks of discontinuing prednisone).

          6. Patient is currently in relapse of nephrotic syndrome or had a relapse within the last
             4 months (defined as an increase in the first morning urine protein to creatinine
             ratio ≥2 or Albustix reading of ≥2 for 3 or 5 consecutive days).

        Exclusion Criteria:

          1. Prior treatment with ACTH.

          2. Cyclophosphamide or rituximab within the last 4 months.

          3. Lactation, pregnancy, or refusal of birth control in females with child-bearing
             potential

          4. Planned treatment with live or live-attenuated vaccines once enrolled in the study.

          5. Participation in another therapeutic trial concurrently or 30 days prior to
             randomization

          6. Active/serious infection (including, but not limited to Hepatitis B or C, HIV)

          7. Malignancy concurrently or within the last 2 years.

          8. Blood pressure >95% for age/height while receiving maximal doses of 3 or more
             medications.

          9. Prior diagnosis of diabetes mellitus (Type I or II) or fasting glucose >200mg/dL

         10. Organ transplantation

         11. Contraindications to Acthar: scleroderma, osteoporosis, systemic fungal infections,
             ocular herpes simplex, recent surgery, history of or the presence of peptic ulcer,
             congestive heart failure, uncontrolled hypertension, primary adrenocortical
             insufficiency, or adrenal cortical hyperfunction

         12. Secondary cause of nephrotic syndrome (e.g., SLE)

         13. Biopsy demonstrating a diagnosis other than minimal change, focal segmental
             glomerulosclerosis (FSGS) or a variant (mesangial proliferation, Immunoglobulin M
             nephropathy)

         14. Inability to consent/assent -