Open Label Phase IIa Study Evaluating the Safety and Efficacy of NE3107 in Improving Sleep and Fatigue in Subjects With Traumatic Brain Injury
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 4
- 试验地点
- 1
- 主要终点
- Safety as Assessed by Quantification of Adverse Events
研究概览
简要总结
This study seeks to measure changes in cognition through verbal and visual test procedures and changes in biomarkers of Traumatic Brain Injury and inflammatory and metabolic parameters.
详细描述
A growing body of literature recognizes neuroinflammation as a pivotal contributor to the pathogenesis of TBI. A surge of inflammatory cytokines and chemokines, including tumor necrosis factor-alpha (TNF-α), interleukin-1 (IL-1), interleukin-6 (IL-6), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB), often follows TBI, leading to a complex cascade of secondary events that ultimately result in neuronal damage and long-term consequences.
It has been shown that patients with mild TBI have higher plasma inflammatory cytokine levels than those without TBI at both 24 hours and 6 months following initial injury.The activation of these inflammatory mediators has been demonstrated in both cerebrospinal fluid (CSF) and serum of TBI patients. Elevated levels of TNF-α in CSF and serum have been associated with injury severity and unfavorable outcomes in TBI.
IL-1, IL-6, and TNF-α induce the extracellular signal-regulated kinase (ERK) pathway, promoting neuroinflammation. Furthermore, NF-kB, a crucial transcription factor in the inflammatory response, plays a significant role in amplifying neuroinflammation post-TBI, mediating the expression of several inflammatory cytokines and contributing to neuronal apoptosis and cognitive impairment.
Neuroinflammation's contribution to sleep disturbances, fatigue, and cognitive impairment has been increasingly recognized. These inflammatory cytokines may influence the hypothalamic-pituitary-adrenal (HPA) axis and disrupt sleep architecture, leading to sleep disturbances and fatigue. Further, they are known to induce synaptic alterations and neuronal apoptosis, contributing to cognitive impairment.
Chronic, low-grade inflammation often ensues post-TBI, contributing to the persistent and potentially insidious process leading to long-term impairment and diminished quality of life.
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
- 18 Years 至 74 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of traumatic brain injury, confirmed by neurologist or other medical professional
- •Age within range of 18-75 years old
- •Multidimensional Fatigue Inventory (MFI) score of 27 or greater
- •Epworth Sleepiness Scale (ESS) score of 10 or greater AND/OR a Pittsburgh Sleep Index (PSI) score of 5 or greater
- •Ability to Consent: Participants need to be capable of giving informed consent or have a legally authorized representative who can do so.
- •Ability to participate for the duration of the study
排除标准
- •In order for a subject to be considered for this study, he/she may NOT have any of the following:
- •Diagnosis of other chronic Neurological Conditions: Examples are participants with other pre-existing neurological conditions, such as Alzheimer's or Parkinson's Disease or untreated epilepsy.
- •Severe Psychiatric Illness: Conditions such as schizophrenia, bipolar disorder, or severe depression.
- •Current diagnosis of Substance Abuse Disorder, including opioid use disorder.
- •Dysphagia or Significant GI dysmotility or conditions that would significantly impair absorption
- •Significant language impairment with expressive or receptive aphasia
- •Hematological or Metabolic derangement or diagnosis of other medical condition that could be negatively affected by participating in this clinical trial.
- •Pregnant or plans for pregnancy or breastfeeding during the course of the study
- •Diagnosis of genetic or developmental disorder with cognitive impairment
- •Use of more than 2 sleep aids including melatonin
- •Advanced stages of any terminal illness or any active cancer that requires chemotherapy
- •History of breast cancer
- •Women with child-bearing potential who are not willing to use a double-barrier birth control method
- •Males not willing to use a double-barrier birth control method with female sex partners with child-bearing potential
- •Individuals with hepatic impairment as defined by:
- •Alanine aminotransferase (ALT) lab values >3x the upper normal limit (UNL)
- •Aspartate aminotransferase (AST) lab values >3x UNL
- •History of clinically significant liver disease in the Principal Investigator's medical judgment
- •Individuals with renal impairment as defined by Creatinine clearance (Cockcroft-Gault formula) of <45 mL/min.
研究组 & 干预措施
Experimental Arm: NE3107
All participants will take 200mg BID (12 hours apart) of NE3107 for 6 months.
干预措施: NE3107 (Drug)
结局指标
主要结局
Safety as Assessed by Quantification of Adverse Events
时间窗: up to 6 months
Primary outcome will be collection of AEs and SAEs
Pittsburgh Sleep Quality Index (PSQI)
时间窗: Baseline, 3 months, 6 months
a tool used to measure the quality and patterns of sleep
Multidimensional Fatigue Inventory (MFI)
时间窗: Baseline, 3 Months, 6 Months
to measure overall fatigue
次要结局
- Montreal Objective Cognitive Assessment change(Baseline, 3 Months, 6 Months)