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

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ClinicalTrials.gov Identifier: NCT03042637
Recruitment Status : Unknown
Verified February 2017 by James A. Tumlin MD, Southeast Renal Research Institute.
Recruitment status was:  Active, not recruiting
First Posted : February 3, 2017
Last Update Posted : February 3, 2017
Sponsor:
Information provided by (Responsible Party):
James A. Tumlin MD, Southeast Renal Research Institute

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 mechanisms that contribute to these disorders as well as the lack of adequately powered, controlled trials. While glucocorticoids remain the primary therapy for many forms of protein uric glomerular 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 studies have examined the efficacy of combining intravenous cyclophosphamide with corticosteroids 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 CNI-induced nephrotoxicity and progressive renal disease. Acthar gel is a porcine pituitary preparation composed of ACTH and other proopiomelanocortin peptides and is currently approved for treatment of idiopathic nephrotic syndrome. Previous studies, as well as more current studies, have shown that ACTHar gel can effectively reduce proteinuria 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 that activation of this receptor pathway could be involved in the protein lowering effects of ACTHar gel. 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.

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Study Type : Observational
Actual Enrollment : 26 participants
Observational Model: Case-Only
Time Perspective: Prospective
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 2017

Resource links provided by the National Library of Medicine


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




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.



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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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03042637


Locations
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United States, Tennessee
Southeast Renal Research Institute
Chattanooga, Tennessee, United States, 37408
Sponsors and Collaborators
Southeast Renal Research Institute
Investigators
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Principal Investigator: James A Tumlin, MD NephroNet Clinical Research Consortium

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Responsible Party: James A. Tumlin MD, Principal Investigator, Southeast Renal Research Institute
ClinicalTrials.gov Identifier: NCT03042637     History of Changes
Other Study ID Numbers: NephroNet-1
First Posted: February 3, 2017    Key Record Dates
Last Update Posted: February 3, 2017
Last Verified: February 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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

Additional relevant MeSH terms:
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Syndrome
Nephrotic Syndrome
Nephrosis
Disease
Pathologic Processes
Kidney Diseases
Urologic Diseases
Tacrolimus
Adrenocorticotropic Hormone
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Calcineurin Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists