Valproic Acid for Idiopathic Nephrotic Syndrome

Focal Segmental Glomerulosclerosis Clinical Trial

— VAIN  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02896270
• Other study ID #: UZB_20160728
• Status: Recruiting
• Phase: Phase 2/Phase 3
• First received: September 6, 2016
• Last updated: June 16, 2017
• Start date: October 2016
• Est. completion date: December 2019

Study information

• Verified date: June 2017
• Source: Universitair Ziekenhuis Brussel
• Contact: Peter Janssens, MD
• Phone: +32 2 477 6224
• Email: peter.janssens[@]uzbrussel.be
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 15
• Est. completion date: December 2019
• Est. primary completion date: October 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Focal Segmental Glomerulosclerosis
• Glomerulosclerosis, Focal Segmental
• Idiopathic Nephrotic Syndrome
• Minimal Change Disease
• Nephrosis
• Nephrosis, Lipoid
• Nephrotic Syndrome
• Syndrome

Intervention

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.

Locations

Country	Name	City	State
Belgium	University Hospital Brussels	Brussels
Belgium	UVC Brugmann	Brussels

Sponsors (1)

Lead Sponsor	Collaborator
Universitair Ziekenhuis Brussel

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	Evaluate the evolution of renal function estimated by MDRD-GFR	Evolution of renal function estimated by CKD-EPI	12 months
Secondary	Evaluate the tolerability of VPA in the setting of idiopathic podocytopathies	Evaluation adverse events	12 months