Open-Label Trial of Sulforaphane in Premutation Carriers With FXTAS to Find Biomarkers
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 15
- 试验地点
- 2
- 主要终点
- Changes in mitochondrial function via mitochondrial membrane potential and mass.
研究概览
简要总结
FXTAS is a rare genetic progressive neurodegenerative disorder, linked to a trinucleotide repeat expansion in the FMR1 gene. FXTAS is characterized by tremor and ataxia in addition to atrophy and white matter disease in the central nervous system (CNS). In addition to the major clinical observations of intention tremor and gait dysfunction, minor symptoms of parkinsonism, neuropathy, and cognitive decline also significantly impact individuals with FXTAS.
The dietary supplement being tested in this study is called Sulforaphane. It is found in broccoli and similar cruciferous vegetables and may cause some gas and discomfort. This is not a study looking at clinical efficacy but instead a study of molecular outcome measures. Investigators want to get more information about how Sulforaphane affects specific biomolecular markers captured in blood.
In this study, participants will be taking an increasing amount of the Sulphoraphane supplement pills (238mg/tablet), starting at 1 and increasing to 6, every morning at breakfast for 6 months. In addition, there will be a total of 3 visits (Initial, 3-month and 6-month) to the MIND Institute where participants will be evaluated. At each visit (3 total) participants will undergo a battery of medical and neurologic exams which make take 2-3 days to complete each time. Participants and/or their caregivers will also be asked to fill out questionnaires/surveys. At the initial visit and at 6 months, we will collect blood for analysis. Two MRI scans will be done, also at the initial visit and at 6 months.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 50 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of FXTAS
- •Presence of a FMR1 premutation (55 to 200 CGG repeats)
排除标准
- •Individuals with severe renal failure (GFR is <60 ml/min/1.73 m^2)
- •Significant and current reported substance abuse
- •Individuals with substance use disorder (meets 6 or more symptoms of substance use disorder criteria)
- •Any subject on hospice or on home oxygen
- •Individuals who are pregnant
结局指标
主要结局
Changes in mitochondrial function via mitochondrial membrane potential and mass.
时间窗: Baseline, 6 months
Primary measures are performed on PBMCs. Mitochondrial mass and membrane potential will use selected floors and either plate readers or analytical flow cytometry.
Changes in mitochondrial function via ATP production
时间窗: Baseline, 6 months
Using PMBCs we will observe in changes in ATP production of various segments of the electron transport chain by utilizing different substrates and coupling between electron transport and ATP production.
Observing changes in candidate molecular biomarkers in FXTAS and mitochondrial dysregulation: GRP78
时间窗: Baseline, 6 months
Observing levels in potential molecular biomarkers that affect mitochondrial dysregulation. GRP78 is a master controller of the mitochondrial ER stress response. It helps improve Ca2+ transfer and mitochondrial function. Its level will be measured via ELISA
Observing changes in candidate molecular biomarkers in FXTAS and mitochondrial dysregulation: CHOP level
时间窗: baseline, 6 months
Observing levels in potential molecular biomarkers that affect mitochondrial dysregulation. CHOP is a common downstream indicator of mitochondrial ER stress signals. It helps improve Ca2+ transfer and mitochondrial function. Its level will be measured via ELISA
Observing changes in candidate molecular biomarkers in FXTAS and mitochondrial dysregulation: Bax/Bcl-2 ratio
时间窗: baseline, 6 months
Observing levels in potential molecular biomarkers that affect mitochondrial dysregulation. Bax/Bcl-2 is a common measure of mitochondrial dysfunction. It helps improve Ca2+ transfer and mitochondrial function. It will be measure via Elisa.
次要结局
- Changes in subcortical brain structures damaged in FXTAS through MRI imaging(Baseline, 6 months)
- Changes in gait variability(Baseline, 6 months)
- Changes in kinetic, postural, and rest tremor upper extremity bradykinesia, hypokinesia, dysrhythmia, and dyskinesias(Baseline, 6 months)
- Changes in executive function deficits using BDS-2(Baseline, 6 months)
- Changes in motor movements(Baseline, 6 months)
- Changes in clinical staging of FXTAS(Baseline, 6 months)
- Changes in FLAIR hypersensitivity volume for subcortical lesions(Baseline, 6 months)
- Changes in Neurological Quality of Life using the Neuro-QoL upper extremity function fine motor scale(Baseline, 6 months)
- Changes in Neurological Quality of Life using the Neuro-QoL lower extremity functioning mobility scale(Baseline, 6 months)
- Changes in psychological Issues(Baseline, 6 months)
- Changes in Grip Strength(Baseline, 6 months)
- Changes in cognitive dysfunction using MoCA(Baseline, 6 months)
- Changes in cognitive dysfunction using MMSE(Baseline, 6 months)
- Changes in executive function deficits using COWAT(Baseline, 6 months)
- Changes in frontal executive planning(Baseline, 6 months)
- Changes in Hippocampus-mediated memory deficits(Baseline, 6 months)
- Changes in cognitive ability(Baseline)
- Changes in dexterity, tremor, and bradykinesia abnormalities(Baseline, 6 months)