Safety and Efficacy of Combination Acthar Gel and Tacrolimus in the Treatment of Steroid Resistant Nephrotic Syndrome

Study Overview
=================
Brief Summary
-----------------
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.

Detailed Description
-----------------
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.

Official Title
-----------------
Safety and Efficacy of Combination Acthar Gel and Tacrolimus in the Treatment of Steroid Resistant Nephrotic Syndrome

Conditions
-----------------
Nephrotic Syndrome

Intervention / Treatment
-----------------
* Drug: Acthar Gel and Tacrolimus


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: refractory nephrotic syndrome secondary, defined as subjects having a urine protein/Cr ratio over 3.0 while actively receiving ACE inhibitors and hyperglycemic therapy (i.e., insulin or oral hyperglycemic agents). Type I or Type II diabetes receiving combination therapy with an ACE inhibitor and a second protein lowering agent (e.g., ARB, non dihydropyridine CCB, or spironolactone). Exclusion Criteria: known primary or secondary membranous glomerulonephritis (GN) primary or secondary focal segmental glomerulosclerosis other nondiabetic forms of glomerulopathy

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Acthar Gel and Tacrolimus<br>Combination therapy with Acthar Gel and Tacrolimus | Drug: Acthar Gel and Tacrolimus<br>* Combination therapy with Acthar Gel and Tacrolimus (0.5-3.0 mg BID) following 6 months of ACTH therapy only<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction of proteinuria in idiopathic membranous glomerulonephritis (MGN) and other forms of glomerulopathy including focal segmental glomerulosclerosis (FSGS) and advanced diabetic nephropathy | 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. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Partial remission or no response to treatment regiment | 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. | 6 months |