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Valproic Acid for Idiopathic Nephrotic Syndrome (VAIN)

Primary Purpose

Idiopathic Nephrotic Syndrome, Focal Segmental Glomerulosclerosis, Minimal Change Disease

Status
Unknown status
Phase
Phase 2
Locations
Belgium
Study Type
Interventional
Intervention
Valproic Acid
Sponsored by
Universitair Ziekenhuis Brussel
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Idiopathic Nephrotic Syndrome focused on measuring idiopathic podocytopathies, Neprology

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University Hospital BrusselsRecruiting
  • UVC BrugmannRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

single arm

Arm Description

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.

Outcomes

Primary Outcome Measures

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.
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

Secondary Outcome Measures

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

Full Information

First Posted
September 6, 2016
Last Updated
June 16, 2017
Sponsor
Universitair Ziekenhuis Brussel
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1. Study Identification

Unique Protocol Identification Number
NCT02896270
Brief Title
Valproic Acid for Idiopathic Nephrotic Syndrome
Acronym
VAIN
Official Title
A Prospective Interventional Pilot Study on the Use of Valproic Acid for Treatment of Idiopathic Nephrotic Syndrome
Study Type
Interventional

2. Study Status

Record Verification Date
June 2017
Overall Recruitment Status
Unknown status
Study Start Date
October 2016 (Actual)
Primary Completion Date
October 2019 (Anticipated)
Study Completion Date
December 2019 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Universitair Ziekenhuis Brussel

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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 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. VPA is effective in remission maintenance allowing reduction and cessation of chronic immunosuppression without relapse in patients with frequently relapsing FSGS or MCD.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Idiopathic Nephrotic Syndrome, Focal Segmental Glomerulosclerosis, Minimal Change Disease
Keywords
idiopathic podocytopathies, Neprology

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
single arm
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Valproic Acid
Other Intervention Name(s)
Depakine Chrono 500©, Sanofi
Intervention Description
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.
Primary Outcome Measure Information:
Title
In remission group induction is the proportion of patients in complete remission
Description
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.
Time Frame
6 months
Title
In remission maintenance group is the proportion of patients able to reduce maintenance
Description
The proportion of patients able to reduce maintenance immunosuppression to a monotherapy of 4 mg methylprednisolone or less while remaining in complete remission
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Determine the disease response by the proportion of subjects with partial remission
Description
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.
Time Frame
6 - 12 months
Title
Determine the extent to which standard immunosuppression can be reduced
Description
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.
Time Frame
6 - 12 months
Title
Evaluate the evolution of renal function estimated by MDRD-GFR
Description
Evolution of renal function estimated by CKD-EPI
Time Frame
12 months
Title
Evaluate the tolerability of VPA in the setting of idiopathic podocytopathies
Description
Evaluation adverse events
Time Frame
12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Peter Janssens, MD
Phone
+32 2 477 6224
Email
peter.janssens@uzbrussel.be
First Name & Middle Initial & Last Name or Official Title & Degree
Nathalie Marmitte, Coordinator
Phone
+32 2 477 6224
Email
nathalie.marmitte@uzbrussel.be
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Peter Janssens, MD
Organizational Affiliation
University Hospital Brussels, Belgium
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Hospital Brussels
City
Brussels
ZIP/Postal Code
1090
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Peter Janssens, MD
Phone
+32 2 477 6224
Email
Peter.Janssens@uzbrussel.be
First Name & Middle Initial & Last Name & Degree
Nathalie Marmitte, Coordinator
Phone
+32 2 477 6224
Email
Nathalie.Marmitte@uzbrussel.be
Facility Name
UVC Brugmann
City
Brussels
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tatiana Besse-Hammer, MD

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
The data of this pilot study will be submitted for publication as soon as the anticipated 15 subjects have completed the study.

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Valproic Acid for Idiopathic Nephrotic Syndrome

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