Cardiac Output and Fatigue in Friedreich's Ataxia
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Adverse events (Primary outcome for Aim 1)
研究概览
简要总结
This is a clinical trial examining to impact of aerobic training plus omaveloxolone in FRDA. Thirty individuals with FRDA will be recruited; 20 individuals will be on omaveloxolone treatment whereas the other ten individuals will not. Individuals will undergo baseline assessment including cardiopulmonary exercise testing (CPET), mFARS, gait speed, Timed Up and Go (TUG), Fatigue Severity Scale (FSS), Fatigue Impact Scale (FIS), and 6-minute Walk Test (6MWT). Individuals will then perform 3-months of home aerobic training. Repeat assessments will be conducted at 3- and 6-months.
详细描述
In February 2023, omaveloxolone became the first Food and Drug Administration (FDA) approved medication for Friedreich's Ataxia (FRDA). In its pivotal study, named MOXIe, researchers found that omaveloxolone significantly improved neurological function compared to placebo. The primary outcome measure was the modified Friedreich's Ataxia Rating Scale (mFARS), the gold standard for measuring ataxia symptoms in clinical trials for FRDA. However, there are several limitations with the use of mFARS:
- It does not detect subtle disease progression over short time frames. For example, in MOXIe, differences between placebo and omaveloxolone were not detected until 48 weeks.
- Some of the components of mFARS rely on clinical judgment, which can introduce variability between raters.
- The minimal clinical important difference (MCID) for mFARS has not been clearly defined.
- The scale lacks sensitivity to detect changes in individuals with minimal symptoms or advanced disease.
Given these limitations, development of additional outcome measures for clinical trials to determine the impact of drugs like omaveloxolone is desirable. In this study, investigators propose using maximal oxygen consumption (VO2max) as a future primary outcome measure for FRDA clinical trials. VO2max offers several advantages as an outcome measure:
- It is a direct physiological measure of aerobic capacity, reducing subjectivity compared to clinical scales like mFARS.
- It can detect subtle changes in aerobic function making it useful for monitoring intervention effects over time.
- It has a defined MCID, and higher VO2max is associated with better health outcomes making it a clinically meaningful endpoint.
- It is non-invasive and reproducible.
To examine the utility of VO2max as a primary outcome measure, this study will recruit 30 individuals with FRDA in this pilot study. Twenty individuals will be on omaveloxolone treatment whereas the other 10 individuals will not. Individuals will undergo baseline cardiopulmonary exercise testing (CPET) to determine VO2max. Secondary measures will include cardiac output. All participants will be given a recumbent bicycle for home use. Participants will be expected to cycle 30-minutes per session, 5x per week at 65-75% maximum heart rate (moderate intensity) for 3-months. To track training, individuals will be given a Fitbit Charge 6, and an exercise physiologist will call every two weeks to adjust training as needed. To determine benefits of training with omaveloxolone, repeat assessments will occur at 3- and 6-months.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Genetically confirmed FRDA
- •Ability to safely ride a stationary bicycle (mFARS sitting posture sub-score <2)
排除标准
- •Beck depression score >19, a score that precludes ability to exercise.
- •Montreal Cognitive Assessment (MoCA) score <23/30
- •Disorders that interfere with ability to perform endurance exercise (e.g., stroke, respiratory problems, traumatic brain injury, or neuromuscular disease).
- •Regular participation in vigorous endurance exercise (defined as >2 days/week for at least the past 4 months at max HR>65%).
- •Evidence of serious arrhythmias or ischemic heart disease.
研究组 & 干预措施
Home Aerobic Training on Omaveloxolone
Participants who are currently taking Skyclarys (omaveloxolone) will be given a recumbent exercise bike (Marcy ME-709 Adjustable Recumbent Exercise Bike, Pomona, CA) for home use. They will be instructed to exercise five times a week. The regimen will include 5-minute warm up, 30 minutes of exercise at target heart rate, and 5 minutes of cool down.
干预措施: Aerobic Exercise (Behavioral)
Home Aerobic Training off Omaveloxolone
Participants who are not taking Skyclarys (omaveloxolone) will be given a recumbent exercise bike (Marcy ME-709 Adjustable Recumbent Exercise Bike, Pomona, CA) for home use. They will be instructed to exercise five times a week. The regimen will include 5-minute warm up, 30 minutes of exercise at target heart rate, and 5 minutes of cool down.
干预措施: Aerobic Exercise (Behavioral)
结局指标
主要结局
Adverse events (Primary outcome for Aim 1)
时间窗: 0, 3, 6 months
Adverse events are defined as exercise-related discomforts (muscle and joint pain), minor injuries (strains, sprains), and non-injurious falls. Serious adverse events are defined as hospitalization, surgery, death, or permanent disability. We will compare adverse and serious adverse events for both groups.
Maximal Oxygen Consumption (primary outcome measure for Aim 2)
时间窗: 0, 3-, 6-months
Maximal oxygen consumption (VO2max) will be determined by a breath-by-breath measurement of VO2 with a Vmax Encore Metabolic System, while participants perform a progressive ramped exercise test using an electronic-braked lower body cycle ergometer (CareFusion Corp, San Diego, CA). The minimal clinically important difference (MCID) has been determined to be between 1.0-2.0 mL/kg/min.
Fatigue Severity scale (primary outcome measure for Aim 3)
时间窗: 0, 3-, and 6-months
A commonly used measure to assess fatigue in a variety of populations. A score change of 3.5 to 4.5 points is considered clinically meaningful.
次要结局
- 6-Minute Walk Test(0, 3-, and 6-months)
- Fatigue Impact Scale(0, 3-, 6-months)
- Cardiac Output(0, 3-, and 6-months)
- Timed Up and Go(0, 3-, and 6-months)
- Gait Speed(0, 3-, 6-months)
- mFARS(0, 3-, 6-months)
- Exercise Adherence(0, 3-, 6-months)
研究者
Scott Barbuto
Assistant Professor at Columbia University Medical Center
Columbia University