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

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.

Study Overview

• Status: Suspended
• Conditions: Nephrotic Syndrome
• Intervention / Treatment: Drug: Acthar Gel and Tacrolimus

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.

• Study Type: Observational

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Chattanooga, Tennessee, United States, 37408
      • Nephronet

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

patients between the ages of 18 and 80 with refractory nephrotic syndrome secondary to Type I or Type II diabetes

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Acthar Gel and Tacrolimus; Combination therapy with Acthar Gel and Tacrolimus	Drug: Acthar Gel and Tacrolimus; Combination therapy with Acthar Gel and Tacrolimus (0.5-3.0 mg BID) following 6 months of ACTH therapy only

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

Collaborators and Investigators

• Sponsor: Southeast Renal Research Institute
• Investigators: Principal Investigator: James A Tumlin, MD, NephroNet Clinical Research Consortium

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 1, 2012
• Primary Completion (ACTUAL): December 1, 2016
• Study Completion (ANTICIPATED): December 1, 2021

Study Registration Dates

• First Submitted: March 30, 2016
• First Submitted That Met QC Criteria: February 1, 2017
• First Posted (ESTIMATE): February 3, 2017

Study Record Updates

• Last Update Posted (ACTUAL): February 17, 2021
• Last Update Submitted That Met QC Criteria: February 15, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Kidney Diseases; Urologic Diseases; Disease; Syndrome; Nephrotic Syndrome; Nephrosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Calcineurin Inhibitors; Tacrolimus
• Other Study ID Numbers: 12345 (Danish Center for Healthcare Improvements)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No