Open-label Pilot Study of Methylprednisolone for the Treatment of Patients With Friedreich Ataxia (FRDA)
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 入组人数
- 11
- 试验地点
- 1
- 主要终点
- Change in the Timed 25 Foot Walk (T25FW) Score
研究概览
简要总结
This study will explore whether methylprednisolone treatment is safe, well-tolerated, and beneficial in patients that are diagnosed with Friedreich Ataxia (FRDA). The study will also explore if methylprednisolone has any effects on biomarkers associated with FRDA. All subjects in the study will receive the same steroid treatment.
详细描述
Context:
Friedreich ataxia (FRDA) is a progressive neurodegenerative disease of children and adults for which there is presently no therapy. One of the hallmarks of FRDA is a deficiency of frataxin protein, causing dysregulation of iron metabolism, lack of detoxification, and increased iron bioavailability. The accumulation of iron in mitochondria leads to increased sensitivity to oxidative stress. A secondary inflammatory response has also been proposed to be present in FRDA, as revealed in autopsy studies and in the alteration of immune pathways in microarray analysis. Inflammation in FRDA raises the possibility of a therapeutic benefit from anti-inflammatory steroid treatment, as inflammation may directly underlie multiple complications of FRDA including cardiomyopathy. In support of this theory are clinical observations and patient self-reports of improvement of ataxia symptoms following the prescription of steroids for indications other than the primary FRDA diagnosis.
Objectives:
Primary: To assess the effect of oral administration of methylprednisolone on the functional performance scores of patients with FRDA using the Timed 25-Foot Walk (T25FW).
Secondary: To assess the effect of methylprednisolone on neurological performance measures (Friedreich Ataxia Rating Scale, 9-Hole Peg Test, 1-minute walk, home-based measures of gait, hand function and speech assessed through smartphone application) and to assess the safety and tolerability of methylprednisolone in the FRDA population.
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
- 5 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects with FRDA confirmed by genetic testing who are able to walk 25 feet (assistive devices allowed).
- •Children between ages 5 and less than 10 years or adults ages 45 years and older at screening.
- •Stable doses of all medications, vitamins and supplements for 30 days prior to study entry and for the duration of the study. Throughout the study, all possible efforts will be made to maintain stable doses of concomitant medications.
- •Females who are not pregnant or breast feeding, and who do not intend to become pregnant. Females of child-bearing potential must use a reliable method of contraception and must provide a negative urine pregnancy test at screening.
- •Informed consent for adult participants, parent/guardian permission (informed consent) and child assent for pediatric participants.
排除标准
- •Patients unable to walk 25 feet.
- •Treatment with methylprednisolone or cyclic methylprednisolone during the 3 previous months before inclusion.
- •Treatment with gamma interferon, immunoglobulin G or other immunomodulating treatment the 3 previous month before inclusion
- •Immunosuppressive treatment within 6 month of inclusion
- •Prior history of a disease associated with immune dysfunction
- •Poorly controlled Diabetes Mellitus (HbA1C > 9.0)
- •History of untreated or uncontrolled hypertension
- •Presence of infectious disease or other active infections which the treating physician finds relevant
- •Active or previous history of liver or renal failure
- •Known history of renal insufficiency or creatinine > 2 x upper limit of normal (ULN)
- •Active infection at time of screening
- •History of known osteoporosis
研究组 & 干预措施
Methylprednisolone
This is an open-label study of methylprednisolone in patients with FRDA. Subjects will begin oral administration of 48 mg methylprednisolone at day 1 and will decrease their administered dose by 8 mg per day. After 6 days, subjects will spend 22 days off medication before repeating the same treatment cycle. Last dosing cycle of methylprednisolone will be administered at 24 weeks after baseline. Visits will occur at weeks 2, 6, 14, 26, and 30 following baseline.
干预措施: Methylprednisolone (Drug)
结局指标
主要结局
Change in the Timed 25 Foot Walk (T25FW) Score
时间窗: This outcome will be measured at baseline and 26 weeks
The T25FW is a quantitative mobility and leg function performance test based on a timed 25-foot walk. The subject is directed to one end of a clearly marked 25-foot course and is instructed to walk 25 feet as quickly as possible. The time is calculated from the initiation of the instruction to start and ends when the subject has reached the 25-foot mark. The task is immediately administered again by having the subject walk back the same distance. Subjects may use assistive devices when doing this task.
次要结局
- Change in the Friedreich Ataxia Rating Scale (FARS) Score(This outcome will be measured at baseline and 26 weeks)
- Change in the Change in the 9-Hole Peg Test (9HPT) Time(This outcome will be measured at baseline and 26 weeks)
- Change in The 1-Minute Walk Distance(This outcome will be measured at baseline and 26 weeks)