Ignite Creation Date:
2025-12-25 @ 4:18 AM
Ignite Modification Date:
2025-12-26 @ 3:19 AM
Study NCT ID:
NCT00098020
Status:
COMPLETED
Last Update Posted:
2017-12-13
First Post:
2004-12-01
Is NOT Gene Therapy:
False
Has Adverse Events:
True
Brief Title:
Podocyte Retinoids
Sponsor:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Organization:
Study Overview
Official Title:
Retinoids for Podocyte Disease
Status:
COMPLETED
Status Verified Date:
2017-10-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This is a pilot study of retinoids for patients with unsatisfactory response to conventional treatment of nephrotic syndrome due to focal segmental glomerulosclerosis or minimal change disease, two renal disorders associated with putatively pathogenic malfunctioning of glomerular podocytes. The hypothesis that retinoids may have reparative effects on these cells is based on previous research showing that retinoids promote the differentiation or redifferentiation of aberrant epithelial cells. Results obtained by 6 months of treatment with retinoids (that have been approved for non-renal indications) will be used as preliminary information upon which to base further testing of these agents in formal clinical trials in refractory cases of these nephrotic syndromes.
Detailed Description:
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 investigational new drug (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, in order to evaluate the extent of glomerular injury and interstitial fibrosis, unless they have had a kidney biopsy within the preceding 24 months that is available for review. Laboratory endpoints will include serum and urine cytokine levels and urine levels of podocyte proteins, including nephrin. Toxicity screening will include serum and urine chemistries, psychological profiles, radiographic films of cervical, thoracic spines and calcanei, and bone mass assessment with dual photon excitation absorptiometry (DEXA) at spine and hip.
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, in order to evaluate the extent of glomerular injury and interstitial fibrosis, unless they have had a kidney biopsy within the preceding 24 months that is available for review. Laboratory endpoints will include serum and urine cytokine levels and urine levels of podocyte proteins, including nephrin. Toxicity screening will include serum and urine chemistries, psychological profiles, radiographic films of cervical, thoracic spines and calcanei, and bone mass assessment with dual photon excitation absorptiometry (DEXA) at spine and hip.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| 05-DK-0015 | OTHER | NIH | View |