Valproic Acid for Idiopathic Nephrotic Syndrome

Phase 2

• Conditions: Focal Segmental Glomerulosclerosis; Minimal Change Disease; Idiopathic Nephrotic Syndrome
• Interventions: Drug: Valproic Acid

• Registration Number: NCT02896270
• Lead Sponsor: Universitair Ziekenhuis Brussel

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.

Study Timeline

• Study First Submitted: 2016-09-06
• Study First Submitted QC: 2016-09-06
• Study First Posted: 2016-09-12
• Study Start: 2016-10
• Status Verified: 2017-06
• Last Update Submitted: 2017-06-16
• Last Update Posted: 2017-06-20
• Primary Completion: 2019-10
• Study Completion: 2019-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 15

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
single arm	Valproic Acid	Patients will start study treatment on Day1 and will be treated with a dose of 250mg twice daily of the valproic acid slow release formulation (Depakine Chrono© - Sanofi Pharma Belgium). Control of valproic acid serum levels after 4 to 7 days. The dose will be progressively increased targeting valproic acid serum levels in the target range for use of the drug as an anti-epileptic (50-100µg/ml). During the study, visits will be performed every month and at the end of treatment. The duration of the study is 12 months. Continuation of valproic acid after completion of the study will be at the investigators discretion.

Primary Outcome Measures

Name	Time	Method
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
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.

Secondary Outcome Measures

Name	Time	Method
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 tolerability of VPA in the setting of idiopathic podocytopathies	12 months	Evaluation adverse events
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.
Evaluate the evolution of renal function estimated by MDRD-GFR	12 months	Evolution of renal function estimated by CKD-EPI

Trial Locations

Locations (2)

UVC Brugmann; 🇧🇪 Brussels, Belgium

University Hospital Brussels; 🇧🇪 Brussels, Belgium