Focal Segmental Glomerulosclerosis, Idiopathic Nephrotic Syndrome, Minimal Change Disease
Conditions
Keywords
idiopathic podocytopathies, Neprology
Brief summary
The trial investigates the use of VPA (Valproic Acid) for the treatment of adult patients with biopsy proven idiopathic focal segmentel glomerulosclerosis (FSGS) or minimal change disease (MCD). VPA used as an add-on to steroids might induce clinical remission in a first category of patients and potentially reduce the dose of maintenance immunosuppression required to maintain remission thereafter. In a second category of patients VPA might allow the reduction or even cessation of immunosuppression while clinical remission is maintained.
Detailed description
Idiopathic MCD to treat diseases with a considerable associated morbidity and mortality. Current treatment options are limited, have limited efficacy and a considerable side effect profile. Recent findings in a murine model suggest that VPA treatment in an early phase of renal disease could halt or even prevent the development of proteinuria and the progression of kidney damage. VPA is a commonly used and easy available oral antiepileptic agent with a favorable side effect profile compared to the current standard of care agents for podocytopathies. This trial investigates wether 1. VPA on top of or in substitution of standard of care agents is effective in remission induction in patients with FSGS or MCD with proteinuria resistant to first line therapy with corticosteroids. 2. VPA is effective in remission maintenance allowing reduction and cessation of chronic immunosuppression without relapse in patients with frequently relapsing FSGS or MCD.
Interventions
DRUGValproic Acid
The concomitant immunosuppressive regimen is to be reduced at the discretion of the investigators. It is suggested to lower immunosuppressive therapy only in valproic acid target trough levels have been attained.
Sponsors
Universitair Ziekenhuis Brussel
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Able to give informed consent * Biopsy proven idiopathic FSGS or MCD * Organ function: * Bilirubin/AST/ALT\< 2 ULN * PLT\>100.000 10\*6/L * INR 1.5 except if on anti-vitamin K treatment * Lipase \<1.5 ULN * Creatinine clearance \>30ml/min -
Exclusion criteria
* Contraindication for VPA * Secondary etiologies for FSGS or MCD * Multiple organ transplantation * Currently participating in another clinical trial * Pregnant or lactating women * Women unwilling to take efficient contraceptive measures for the duration of the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| In remission group induction is the proportion of patients in complete remission | 6 months | Complete remission is defined as a reduction of proteinuria to \<300mg/g creatinine or \< 0.3g/d and normal serum creatinine (or stable creatinine if baseline creatinine before disease onset is well documented) and serum albumin \> 3.5g/dL. |
| In remission maintenance group is the proportion of patients able to reduce maintenance | 6 months | The proportion of patients able to reduce maintenance immunosuppression to a monotherapy of 4 mg methylprednisolone or less while remaining in complete remission |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Determine the disease response by the proportion of subjects with partial remission | 6 - 12 months | Remission induction patients with partial remission defined as a reduction in proteinuria to 0.3-3.5g/d or 300-3500mg/g creatinine and a decrease of at least 50% from baseline proteinuria and stable serum creatinine (change in creatinine \< 25%) 6 months after inclusion into the study for FSGS. Remission maintenance patients remaining in remission for at least 6 months after reduction of maintenance immunosuppression to monotherapy with 4 mg of methylprednisolone or less. |
| Determine the extent to which standard immunosuppression can be reduced | 6 - 12 months | The proportion of remission induction patients attaining full or partial remission with 4mg methylprednisolone or less 6 months and 12 months after inclusion; The proportion of remission maintenance patients remaining in remission for at least 6 months after reduction of maintenance immunosuppression to monotherapy with 4 mg of methylprednisolone or less. |
| Evaluate the evolution of renal function estimated by MDRD-GFR | 12 months | Evolution of renal function estimated by CKD-EPI |
| Evaluate the tolerability of VPA in the setting of idiopathic podocytopathies | 12 months | Evaluation adverse events |
Countries
Belgium
Contacts
Primary ContactPeter Janssens, MD
Backup ContactNathalie Marmitte, Coordinator
Outcome results
None listed