A Phase 2a Study of NAD+ Precursor Supplementation in Friedreich's Ataxia
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 7
- 试验地点
- 1
- 主要终点
- Percentage of Individuals With Treatment-emergent Adverse Events as Assessed by Common Terminology Criteria for Adverse Events Version 5.0.
研究概览
简要总结
The primary objective is to test the safety and tolerability of short-term therapy with a nicotinamide adenine dinucleotide (NAD+) precursor (MIB-626) in adults with Friedreich's Ataxia (FA) without overt heart failure and with a left ventricular ejection fraction ≥ 40%. A key secondary objective is to test the effects of MIB-626 on cardiac and skeletal muscle bioenergetics.
详细描述
The primary focus for this protocol is safety and tolerability. We will systematically assess for adverse events using a safety monitoring uniform report form. We will also use cardiac 31-Phosphorus-Magnetic Resonance Spectroscopy (MRS) to measure the Phosphocreatine(PCr)/Adenosine triphosphate (ATP)- γ ratio before and after treatment with MIB-626. In addition, if time permits we will use proton (1H)-MRS to measure skeletal muscle nicotinamide adenine dinucleotide (NAD+) before and after treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 64 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Molecular diagnosis of Friedreich's Ataxia (FA).
- •Males and females, ages 18 years to < 65 years.
排除标准
- •Known sensitivity to nicotinamide-containing compounds.
- •Concurrent use of Vitamin B3 supplements and/or any medications likely to increase risk of MIB-626 toxicity.
- •HgbA1c > (great than or equal to) 8.5% and or Diabetes Mellitus (DM) requiring insulin or insulin secretagogue.
- •Kidney disease (Estimated Glomerular Filtration Rate (eGFR) < 60 ml/min/1.73 m2) using serum creatinine and MDRD equation. The eGFR levels will be calculated using the Modified Diet in Renal Disease Study (MDRD) equation, which is the equation used by the Children's Hospital Of Philadelphia laboratory.
- •Liver disease (Aspartate Aminotransferase (AST)/Alanine Aminotransferase (ALT) > 3 x Upper Limit of Normal)
- •Severe co-existing cardiac disease (Ejection Fraction (EF) < 40%, known arrhythmia) as demonstrated by an echocardiogram within 12 months of screening.
- •Any contraindication to MRI, including spinal rods (related to unknown safety considerations for cardiac 31-Phosphorus -MRS).
- •Use of any investigational agent within 4 weeks of enrollment.
- •Females: Pregnant/lactating or planning to become pregnant during their participation.
- •Any medical condition that, in the opinion of the investigator, will interfere with the safe completion of the study.
研究组 & 干预措施
Open Label - MIB-626
MIB-626
干预措施: MIB-626 (Drug)
结局指标
主要结局
Percentage of Individuals With Treatment-emergent Adverse Events as Assessed by Common Terminology Criteria for Adverse Events Version 5.0.
时间窗: 14 Days
Safety will be monitored through collection of laboratory assessments (CBC, complete metabolic profile, lipid profile, HbA1c), vital signs (heart rate, blood pressure), and ECG, all of which will be reviewed for clinically relevant abnormalities, and standardized assessment of symptoms. We report the proportion of individuals who had at least one treatment-emergent adverse event of Grade 1 or higher.
次要结局
- Cardiac 31-Phosphorus-Magnetic Resonance Spectroscopy (MRS): Phosphocreatine (PCr)/Adenosine Tri-Phosphate (ATP) Ratio(Change from baseline to 14 days.)
- Post-Exercise Creatine Chemical Exchange Saturation Transfer (CrCEST) Magnetic Resonance Imaging (MRI)(Change from baseline to 14 days.)
- Grip Strength(Change from baseline to 14 days.)
- Concentration of Nicotinamide Adenine Dinucleotide (NAD+) in Whole Blood(Change from baseline to 14 days.)
研究者
Shana McCormack
Attending Physician
Children's Hospital of Philadelphia