Valproic Acid for Idiopathic Nephrotic Syndrome (VAIN)

A Prospective Interventional Pilot Study on the Use of Valproic Acid for Treatment of Idiopathic Nephrotic Syndrome

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.

Study Overview

• Status: Unknown
• Conditions: Focal Segmental Glomerulosclerosis; Minimal Change Disease; Idiopathic Nephrotic Syndrome
• Intervention / Treatment: Drug: Valproic Acid

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 Type: Interventional
• Enrollment (Anticipated): 15
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Peter Janssens, MD; Phone Number: +32 2 477 6224; Email: Peter.Janssens@uzbrussel.be
• Study Contact Backup: Name: Nathalie Marmitte, Coordinator; Phone Number: +32 2 477 6224; Email: Nathalie.Marmitte@uzbrussel.be

Study Locations

• Belgium
  • Brussels, Belgium, 1090
    • Recruiting
    • University Hospital Brussels
    • Contact: Peter Janssens, MD; Phone Number: +32 2 477 6224; Email: Peter.Janssens@uzbrussel.be
    • Contact: Nathalie Marmitte, Coordinator; Phone Number: +32 2 477 6224; Email: Nathalie.Marmitte@uzbrussel.be
  • Brussels, Belgium
    • Recruiting
    • UVC Brugmann
    • Contact: Tatiana Besse-Hammer, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: single arm; 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.

Drug: Valproic 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.; Other Names: Depakine Chrono 500©, Sanofi

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
In remission group induction is the proportion of patients in complete remission	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.	6 months
In remission maintenance group is the proportion of patients able to reduce maintenance	The proportion of patients able to reduce maintenance immunosuppression to a monotherapy of 4 mg methylprednisolone or less while remaining in complete remission	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determine the disease response by the proportion of subjects with partial remission	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.	6 - 12 months
Determine the extent to which standard immunosuppression can be reduced	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.	6 - 12 months
Evaluate the evolution of renal function estimated by MDRD-GFR	Evolution of renal function estimated by CKD-EPI	12 months
Evaluate the tolerability of VPA in the setting of idiopathic podocytopathies	Evaluation adverse events	12 months

Collaborators and Investigators

• Sponsor: Universitair Ziekenhuis Brussel
• Investigators: Principal Investigator: Peter Janssens, MD, University Hospital Brussels, Belgium

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2016
• Primary Completion (Anticipated): October 1, 2019
• Study Completion (Anticipated): December 1, 2019

Study Registration Dates

• First Submitted: September 6, 2016
• First Submitted That Met QC Criteria: September 6, 2016
• First Posted (Estimate): September 12, 2016

Study Record Updates

• Last Update Posted (Actual): June 20, 2017
• Last Update Submitted That Met QC Criteria: June 16, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Keywords: idiopathic podocytopathies; Neprology
• Additional Relevant MeSH Terms: Pathologic Processes; Kidney Diseases; Urologic Diseases; Disease; Nephritis; Glomerulonephritis; Syndrome; Glomerulosclerosis, Focal Segmental; Nephrotic Syndrome; Nephrosis; Nephrosis, Lipoid; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Enzyme Inhibitors; Tranquilizing Agents; Psychotropic Drugs; GABA Agents; Anticonvulsants; Antimanic Agents; Valproic Acid
• Other Study ID Numbers: UZB_20160728

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The data of this pilot study will be submitted for publication as soon as the anticipated 15 subjects have completed the study.