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Valproic Acid for Idiopathic Nephrotic Syndrome (VAIN)

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ClinicalTrials.gov Identifier: NCT02896270
Recruitment Status : Unknown
Verified June 2017 by Universitair Ziekenhuis Brussel.
Recruitment status was:  Recruiting
First Posted : September 12, 2016
Last Update Posted : June 20, 2017
Sponsor:
Information provided by (Responsible Party):
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.


Condition or disease Intervention/treatment Phase
Idiopathic Nephrotic Syndrome Focal Segmental Glomerulosclerosis Minimal Change Disease Drug: Valproic Acid Phase 2 Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 15 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Prospective Interventional Pilot Study on the Use of Valproic Acid for Treatment of Idiopathic Nephrotic Syndrome
Actual Study Start Date : October 2016
Estimated Primary Completion Date : October 2019
Estimated Study Completion Date : December 2019


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 Name: Depakine Chrono 500©, Sanofi




Primary Outcome Measures :
  1. In remission group induction is the proportion of patients in complete remission [ Time Frame: 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.

  2. In remission maintenance group is the proportion of patients able to reduce maintenance [ Time Frame: 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 Outcome Measures :
  1. Determine the disease response by the proportion of subjects with partial remission [ Time Frame: 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.


  2. Determine the extent to which standard immunosuppression can be reduced [ Time Frame: 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.

  3. Evaluate the evolution of renal function estimated by MDRD-GFR [ Time Frame: 12 months ]
    Evolution of renal function estimated by CKD-EPI

  4. Evaluate the tolerability of VPA in the setting of idiopathic podocytopathies [ Time Frame: 12 months ]
    Evaluation adverse events



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02896270


Contacts
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Contact: Peter Janssens, MD +32 2 477 6224 peter.janssens@uzbrussel.be
Contact: Nathalie Marmitte, Coordinator +32 2 477 6224 nathalie.marmitte@uzbrussel.be

Locations
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Belgium
University Hospital Brussels Recruiting
Brussels, Belgium, 1090
Contact: Peter Janssens, MD    +32 2 477 6224    Peter.Janssens@uzbrussel.be   
Contact: Nathalie Marmitte, Coordinator    +32 2 477 6224    Nathalie.Marmitte@uzbrussel.be   
UVC Brugmann Recruiting
Brussels, Belgium
Contact: Tatiana Besse-Hammer, MD         
Sponsors and Collaborators
Universitair Ziekenhuis Brussel
Investigators
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Principal Investigator: Peter Janssens, MD University Hospital Brussels, Belgium
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Responsible Party: Universitair Ziekenhuis Brussel
ClinicalTrials.gov Identifier: NCT02896270    
Other Study ID Numbers: UZB_20160728
First Posted: September 12, 2016    Key Record Dates
Last Update Posted: June 20, 2017
Last Verified: June 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: The data of this pilot study will be submitted for publication as soon as the anticipated 15 subjects have completed the study.
Keywords provided by Universitair Ziekenhuis Brussel:
idiopathic podocytopathies
Neprology
Additional relevant MeSH terms:
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Nephrotic Syndrome
Nephrosis
Glomerulosclerosis, Focal Segmental
Nephrosis, Lipoid
Syndrome
Disease
Pathologic Processes
Kidney Diseases
Urologic Diseases
Glomerulonephritis
Nephritis
Valproic Acid
Anticonvulsants
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
GABA Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Antimanic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs