A Prospective Interventional Pilot Study on the Use of Valproic Acid for Treatment of Idiopathic Nephrotic Syndrome
试验速览
- 阶段
- 2 期
- 入组人数
- 15
- 试验地点
- 2
- 主要终点
- In remission maintenance group is the proportion of patients able to reduce maintenance
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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 -
排除标准
- •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
研究组 & 干预措施
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.
干预措施: Valproic Acid (Drug)
结局指标
主要结局
In remission maintenance group is the proportion of patients able to reduce maintenance
时间窗: 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
时间窗: 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.
次要结局
- Determine the extent to which standard immunosuppression can be reduced(6 - 12 months)
- Evaluate the tolerability of VPA in the setting of idiopathic podocytopathies(12 months)
- Determine the disease response by the proportion of subjects with partial remission(6 - 12 months)
- Evaluate the evolution of renal function estimated by MDRD-GFR(12 months)