Adrenocorticotropic Hormone (ACTH) for Frequently Relapsing and Steroid Dependent Nephrotic Syndrome
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 31
- 试验地点
- 16
- 主要终点
- Number of Participants Experienced a Relapse of Nephrotic Syndrome
研究概览
简要总结
In childhood nephrotic syndrome, the kidneys leak protein, causing body swelling and a variety of possible complications such as infection, blood clots, and kidney failure. The first-line treatment for nephrotic syndrome is corticosteroids. Many children respond to prednisone treatment, but the disease comes back (relapses) when the prednisone is stopped or the dose is reduced. Children with frequently relapsing or steroid dependent nephrotic syndrome are at risk for toxicity from frequent exposure to corticosteroids.
Currently, the standard treatment for frequently relapsing and steroid dependent nephrotic syndrome involves a variety of medications that suppress the immune system, which can produce serious side effects. We propose a study to examine the effects of a different medication, ACTH, on nephrotic syndrome. ACTH is a hormone naturally found in the body. Recently, in adult studies, ACTH has been shown to be effective for the treatment of nephrotic syndrome. It has also been shown to have mild and reversible side effects. ACTH is potentially an attractive therapeutic alternative for the treatment of frequently relapsing and steroid dependent nephrotic syndrome in children. Our study will randomly assign patients with frequently relapsing or steroid dependent nephrotic syndrome to either ACTH treatment or no treatment. This will allow us to study the effects of ACTH on this disease and its side effects, by comparing how patients do on ACTH treatment versus no treatment. We hypothesize that ACTH gel is superior to no treatment in maintaining remission in children with frequently relapsing or steroid dependent nephrotic syndrome.
详细描述
Our hypotheses are the following:
Hypothesis 1: ACTH gel is superior to no treatment in maintaining remission in children with frequently relapsing or steroid dependent nephrotic syndrome (NS).
Hypothesis 2: Relapses in children with frequently relapsing or steroid dependent nephrotic syndrome receiving ACTH gel will increase when the dose of ACTH gel is reduced by 50%.
Hypothesis 3: ACTH gel will increase the percentage of children with frequently relapsing or steroid dependent nephrotic syndrome that remain relapse free off medication.
Primary end-points:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 2 Years 至 20 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age >1 year at onset of nephrotic syndrome
- •Age 2-20 years at time of randomization
- •Estimated glomerular filtration rate (GFR) > 50 ml/min/1.73 m2 at most recent measure prior to randomization (Schwartz formula)
- •Steroid responsive nephrotic syndrome throughout clinical course (never required a second agent to attain remission of a relapse of nephrotic syndrome)
- •History of frequently relapsing or steroid dependent nephrotic syndrome (defined as 2 or more relapses within 6 months after initial therapy or 4 or more relapses in any 12 month period OR relapse during taper or within 2 weeks of discontinuing prednisone).
- •Patient is currently in relapse of nephrotic syndrome or had a relapse within the last 4 months (defined as an increase in the first morning urine protein to creatinine ratio ≥2 or Albustix reading of ≥2 for 3 or 5 consecutive days).
排除标准
- •Prior treatment with ACTH.
- •Cyclophosphamide or rituximab within the last 4 months.
- •Lactation, pregnancy, or refusal of birth control in females with child-bearing potential
- •Planned treatment with live or live-attenuated vaccines once enrolled in the study.
- •Participation in another therapeutic trial concurrently or 30 days prior to randomization
- •Active/serious infection (including, but not limited to Hepatitis B or C, HIV)
- •Malignancy concurrently or within the last 2 years.
- •Blood pressure >95% for age/height while receiving maximal doses of 3 or more medications.
- •Prior diagnosis of diabetes mellitus (Type I or II) or fasting glucose >200mg/dL
- •Organ transplantation
- •Contraindications to Acthar: scleroderma, osteoporosis, systemic fungal infections, ocular herpes simplex, recent surgery, history of or the presence of peptic ulcer, congestive heart failure, uncontrolled hypertension, primary adrenocortical insufficiency, or adrenal cortical hyperfunction
- •Secondary cause of nephrotic syndrome (e.g., SLE)
- •Biopsy demonstrating a diagnosis other than minimal change, focal segmental glomerulosclerosis (FSGS) or a variant (mesangial proliferation, Immunoglobulin M nephropathy)
- •Inability to consent/assent -
研究组 & 干预措施
Adrenocorticotropic hormone (ACTH)
Patients will receive ACTH twice weekly subcutaneously The initial dosing will be based on body surface area (BSA): 80 IU/1.73 m2
The patients will receive the initial dose for 6 months. At 6 months, the dose will be reduced by 50%. Patients who have side effects may have the dose reduced by 50% during the initial 6 months. A second dose reduction would still occur at 6 months (25% of initial dose).
干预措施: ACTH (Drug)
Rescue therapy
There is an option for the patient in no-treatment arm to elect to be placed in the active treatment arm of the trial (rescue therapy).
干预措施: ACTH (Drug)
结局指标
主要结局
Number of Participants Experienced a Relapse of Nephrotic Syndrome
时间窗: 6 months
Number of participants experienced a relapse of nephrotic syndrome during the initial 6 months of the study.
次要结局
- Number of Participants Experiencing Relapses After Dose Reduction of ACTH(6 to 12 months)
- Number of Adverse Events(12 months)
研究者
Larry Greenbaum, MD, PhD
Principal Investigator
Emory University