Phase IV Study Safety & Feasibility of Sodium Oxybate in Mild Alzheimer's Disease Patients.
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 发起方
- 入组人数
- 4
- 试验地点
- 1
- 主要终点
- To evaluate and monitor the safety and tolerability of 6 to 9 g/day sodium oxybate in patients with mild Alzheimer's disease (AD) between the ages of 50 and 65 years.
研究概览
简要总结
Eligible patients will undergo this open label initial safety and feasibility study investigating the use of 6 g/day sodium oxybate in mild AD. A total of 5 visits are included with this trial and total subject participation duration of 7-8 weeks. The screening phase will include an initial screening visit and a screening PSG night. After successful screening, subjects will complete a baseline PSG night and undergo a third PSG night to monitor initial safety and compliance with study drug at a dosage of 4.5 g/day of sodium oxybate. Thus the subject will undergo three consecutive nights of PSG in the sleep center. The patient will maintain a dosage of 4.5 g/day for a duration of 7 days leading to Treatment Visit 1. After successful assessment at Treatment Visit 1, the dosage will be increased to 6 g/day for the duration of the trial. At Treatment Visit 2 (day 21), the dosage will be increased to a dosage of 9 g/day, if tolerated by the patient. The remaining visit will occur at 6 weeks after baseline, with Treatment Visit 3 consisting of two consecutive nights of PSG. Participation will be complete after this visit. Phone follow-up will be made at one week post completion visits to assess any wash-out symptoms. Please refer to Figure for flow of the study design.
详细描述
Screening Visit (Day -14 to -7): To avoid confusion, all study visits will occur at the Clayton Sleep Institute. A spouse or caregiver is required to attend all visits.
During the screening visit potential patients will provide informed consent, which must signed by both the patient and the caregiver, followed by a medical and sleep history and physical, completion of the Morse Fall Scale, CDR scale, and the Mini-Mental Status exam (MMSE), as well as the drawing of clinical labs, collection of urine drug screen, and completion of 12-lead ECG. Mild AD patients must have a previous clinical diagnosis according to established criteria. Review of concomitant medications, stimulant usage, and vital signs will also be recorded. In order to assess for sleep quality, the Pittsburgh Sleep Quality Index (PSQI) will be administered.
Participants who meet study criteria will be asked to continuously wear a wrist actigraph (Actiwatch Score; Mini Mitter Co., Inc, Sunriver, OR) from the screening visit through the baseline visit. Each subject will be instructed to press an event button at bedtime and upon awakening in the morning. Data collection will be in 60 second epochs. A handwritten sleep and caregiver diary will be maintained for the duration of the study period to document daily bedtime, wake time, stimulant usage as well as provide daily estimates of sleep latency, total sleep time, and sleep quality, as well as dosing compliance, adverse events, and behavior.
Baseline Visit (Day 0-2): The baseline visit will occur 1-2 weeks after the screening visit to allow for a medication washout period if needed. Participants will be asked to arrive at the sleep center at 7:30 PM each of the three nights. During the evening of all three testing nights, concomitant medication and stimulant usage and adverse events will be reviewed, as well as gait stability assessment and vital signs performed. Night one will consist of a screening PSG to assess for potential sleep disorders. Patients who do not meet exclusion criteria for sleep disorders after night one will be excluded from the study. Participants will be allowed to leave in the morning after the screening PSG and return that evening. Night two will again consist of a full PSG, with this night serving as baseline data.
Two hours after the completion of the PSG, patients will complete a battery of tests measuring daytime functioning, memory function, and neurobehavioral testing. Measures include the Epworth Sleepiness Scale (ESS), Fatigue Severity Scale (FSS), Clayton Daytime Functioning Scale (CDFS), PSQI, PVT, the National Adult Reading Test- Revised (NART-R), Rey Auditory Verbal Learning Test (RAVLT), Kendrick Object Learning Task (KOLT), and the Cambridge Cognitive Examination (CAMCOG). Following the battery of measurements, a study physician will complete the Clinician's Interview-Based Impression of Severity (CIBIS) during this visit for the mild AD patients and complete the Caregiver Distress Scale (NPI-CDS). Finally, the Instrumental Activities of Daily Living (IADL) questionnaire will be given and completed.
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
- 50 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Study inclusion:
- •Ages 50 to 65 years
- •Diagnosis of mild AD according to NINCDS-ACDRA criteria and a CDR scale score of 1.0 indicating mild dementia
- •May be on approved AI's, but on a stable dose > 3 months prior to baseline and maintain dosage for duration of the study
- •A reliable caregiver, who must reside with the patient, must be present and available for the duration of the study and must attend all study visits and spend the night in the sleep center for Night 3 for the baseline visit. Overnight stays for all other PSG procedures is optional for the caregiver
- •Complaint of sleep disturbance as measured by a score of >5 on the Pittsburgh Sleep Quality Index (PSQI)
- •Fluent in the English language
- •Able to comprehend and comply with all study related procedures
排除标准
- •Previous history and diagnosis of a sleep disorder (such as sleep apnea, periodic limb movements, primary insomnia, or narcolepsy)
- •On screening polysomnogram (PSG) an apnea/hypopnea index (AHI) > 15/hr using CMS criteria, oxygen desaturation < 80%, or periodic limb movement arousal index > 10/hr.
- •Current unstable major medical or psychiatric disorder (unrelated to dementia)
- •A history of succinic semialdehyde dehydrogenase (SSADH) deficiency
- •History of seizure disorder or major affective disorder
- •History of substance abuse
- •Poor gait and coordination
- •Currently taking CNS depressants, stimulants, or other medications in the opinion of the investigator that may affect sleep architecture (other than approved AI therapy). Consistent with study drug labeling, patients taking sedative/hypnotics and unable to washout of those medications at least 7 half-lives prior to completion of initial screening will be excluded.
- •Typically consume > 600 mg caffeine in a 24 hour period and/or unwilling to refrain from caffeine consumption within 4 hours of bedtime
- •Any patient, in the opinion of the investigator, that would not be appropriate for participation in the study
结局指标
主要结局
To evaluate and monitor the safety and tolerability of 6 to 9 g/day sodium oxybate in patients with mild Alzheimer's disease (AD) between the ages of 50 and 65 years.
时间窗: 65 days
次要结局
未报告次要终点