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

• ClinicalTrials.gov Identifier: NCT03042637
• Recruitment Status: Suspended
• First Posted: February 3, 2017
• Last Update Posted: February 17, 2021
• Sponsor: Southeast Renal Research Institute
• Information provided by (Responsible Party): James A. Tumlin MD, Southeast Renal Research Institute

Study Description

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.

Condition or disease	Intervention/treatment
Nephrotic Syndrome	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 Design

• Study Type: Observational
• Observational Model: Case-Only
• Time Perspective: Cross-Sectional
• Official Title: Safety and Efficacy of Combination Acthar Gel and Tacrolimus in the Treatment of Steroid Resistant Nephrotic Syndrome
• Actual Study Start Date: January 2012
• Actual Primary Completion Date: December 2016
• Estimated Study Completion Date: December 2021

Groups and Cohorts

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

Outcome Measures

Primary Outcome Measures :

1. 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 ]
   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.

Secondary Outcome Measures :

1. Partial remission or no response to treatment regiment [ Time Frame: 6 months ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• 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

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

Contacts and Locations

Locations

United States, Tennessee

Nephronet

Chattanooga, Tennessee, United States, 37408

Sponsors and Collaborators

Southeast Renal Research Institute

Investigators

• Principal Investigator: James A Tumlin, MD; NephroNet Clinical Research Consortium

More Information

• Responsible Party: James A. Tumlin MD, Principal Investigator, Southeast Renal Research Institute
• ClinicalTrials.gov Identifier: NCT03042637
• Other Study ID Numbers: 12345
• First Posted: February 3, 2017
• Last Update Posted: February 17, 2021
• Last Verified: February 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Nephrotic Syndrome; Nephrosis; Syndrome; Disease; Pathologic Processes; Kidney Diseases; Urologic Diseases; Tacrolimus; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Calcineurin Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action