Podocyte Retinoids

Completed · Phase 2

Conditions studied: Collapsing Glomerulopathy, Glomerulosclerosis, Focal Segmental

In brief

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.

Key facts

Study ID

NCT00098020

Run by

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

People needed

12

Starts

2004-11-26

Expected to finish

2016-06-27

Last updated by the study team

2017-12-13

Who can join

Age: 16 and older. Sex: any. Healthy volunteers: not accepted.

You may not qualify if…

• Pregnancy, breastfeeding, or unwillingness to use at least two contraceptive methods (at least one of which must be primary, including tubal ligation, partner vasectomy, oral contraceptives, implanted contraceptives, and intrauterine device). The rationale is that retinoids are teratogenic and are excreted in breast milk.
• Abnormal liver function test, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin, or protime. The rationale is that retinoids can be hepatotoxic. The only exception will be the following: if the cause of abnormality of liver function tests (LFT) is felt to be due to a specific hepatotoxic drug such as a statin and the levels are less than 2 times the upper limit of the normal AND normalize upon holding the offending drug, patients may be considered for study participation after consultation with hepatology service.
• Hypertriglyceridemia greater than 500 mg/dL despite statin/fibrate therapy. The rationale is that retinoids can increase lipids, particularly triglyceride as this can lead to pancreatitis.
• Any medical conditions requiring concurrent immunosuppression, as this pilot study is designed to evaluate the effect of retinoids as a monotherapy.
• Any medical conditions requiring concurrent use of tetracycline, minocycline, or doxycycline, due to enhanced risk of increased intracranial pressure.
• Hypersensitivity to retinoids.
• Presence of any unstable cardiovascular disease, uncontrolled diabetes with hemoglobin A1c greater than 8 percent, chronic inflammatory or infectious conditions except HIV-1 infection. Retinoids have been associated with chest pain of unclear etiology, increased serum glucose, myelosuppression and increased risk of infection. The etiology of infection is not clear but may be related to myelosuppression.
• Those with HIV-1 infection must not have any evidence for opportunistic infectious complications and have cluster of differentiation 4 (CD4) count greater than or equal to 200. Both tretinoin and isotretinoin have been safely studied in HIV-infected patients for other indications.
• glomerular filtration rate (GFR) less than 40 ml/min/1.73m(2) estimated by 5-variable Modification of Diet in Renal Disease (MDRD) equation, as the metabolites of retinoids are excreted in part in urine, and there is a concern for increased toxicity. In participants less than 18 years of age, we will use Schwartz equation.
• Expansion of glomerulus or interstitial formation on the biopsy.
• Untreated depression, as retinoids have been associated with depression, suicidal ideation, and aggressive behavior. If patients manifest significant depressive symptoms, they will be included in the study only if assessed and agreed by a psychiatrist (either at NIH or other) and if they have regular follow-up visits with a psychiatrist.
• Factors that increase the risk of renal biopsy. These include the following: unwillingness to accept blood transfusion, bleeding diathesis, single kidney, small kidneys (less than 9.5 cm).

Where it is running

• National Institutes of Health Clinical Center, 9000 Rockville Pike — Bethesda, Maryland, United States

Full record on ClinicalTrials.gov

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