Clinical Trial: Retinoids for Minimal Change Disease and Focal Segmental Glomerulosclerosis

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Retinoids for Podocyte Disease

Brief Summary:

Retinoids are analogues of vitamin A that regulate cellular differentiation, leading to therapeutic use in skin disease and malignancy. In animal models of kidney disease, retinoids restore podocyte phenotype toward normal and reduce proteinuria. The objective of this phase II trial is to evaluate safety and develop preliminary evidence of efficacy of retinoid treatment in patients with podocyte disease. The study is an open-label trial of isotretinoin (13-cis retinoic acid). The study will be performed under the auspices of an IND from the FDA. We will enroll 10 adult patients with biopsy-proven minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), or collapsing glomerulopathy (CG). Inclusion criteria will include a prior trial of immunosuppressive therapy and proteinuria greater than or equal to 3.5 g/d while on angiotensin antagonist therapy.

The duration of the trial will be 6 months with possible additional 6-month extension for patients who only develop partial response (PR) or limited response (LR). Those who have complete response (CR) will continue the treatment for one additional month, for no more than 7 months total. Non-responders will stop at the end of 6 months. The primary clinical endpoint will be reduction in proteinuria as compared to the baseline value assessed by paired t test. The secondary clinical endpoints will be the fraction of patients who achieve (CR) or (PR) at 6 months and at one year, confirmed on urine collections four weeks apart. Retinoid therapy will be discontinued at the time a CR is confirmed, one month after the first detection of CR. Follow-up will last one year after cessation of drug therapy. Patients who have had CR or PR, but experience a relapse with greater than 3.5 g/d proteinuria during follow-up will be eligible for further retinoid therapy.

All Participa

Detailed Summary:

Retinoids are analogues of vitamin A that regulate cellular differentiation, leading to therapeutic use in skin diseases and malignancy. In animal models of kidney diseases, retinoids restore podocyte phenotype toward normal and reduce proteinuria. The objective of this phase II trial is to evaluate safety and develop preliminary evidence of efficacy of retinoid treatment in patients with podocyte disease. The study design is an open-label trial of isotretinoin (13-cis retinoic acid). The study will be performed under the auspices of an IND from the FDA. We will enroll 10 adult patients with biopsy-proven minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), or collapsing glomerulopathy (CG). Inclusion criteria will include a prior trial of immunosuppressive therapy and proteinuria greater than or equal to 3.5 g/d while on angiotensin antagonist therapy.

The duration of the trial will be 6 months with possible additional 6-month extension for patients who only develop partial response (PR) or limited response (LR). Those who have complete response (CR) will continue the treatment for one additional month, for no more than 7 months total. Non-responders will stop at the end of 6 months. The primary clinical endpoint will be reduction in proteinuria as compared to the baseline value assessed by paired t test. The secondary clinical endpoints will be the fraction of patients who achieve CR or PR at 6 months and at one year, confirmed on urine collections four weeks apart. Retinoid therapy will be discontinued at the time a CR is confirmed, one month after the first detection of CR. Follow-up will last one year after cessation of drug therapy. Patients who have had a CR or PR but experience a relapse with >2.0g/g proteinuria during follow-up will be eligible for further retinoid therapy. Patients will undergo a renal biopsy prior to initiating therapy, i
Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Current Primary Outcome: Reduction in proteinuria [ Time Frame: 01/31/2018 ]

Original Primary Outcome:

Current Secondary Outcome: Fraction of patients who are in CR or PR at 6 months or at the end of 1 year. Fraction of patients who are in CR or PR1 year after stopping therapy. [ Time Frame: After 10 patients have completed the study ]

Original Secondary Outcome:

Information By: National Institutes of Health Clinical Center (CC)

Dates:
Date Received: December 1, 2004
Date Started: November 26, 2004
Date Completion:
Last Updated: January 24, 2017
Last Verified: January 4, 2017