Identification of Prodromal Neurodegeneration in Serotonergic-Induced REM Sleep Behavior Disorder
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 66
- 试验地点
- 1
- 主要终点
- Neuromelanin signal intensity in the Subcoeruleus/Coeruleus Complex
研究概览
简要总结
This project will test the hypotheses that people with 5-HT RBD have systemic alpha- synuclein pathology, prodromal DLB signs, and brainstem lesions in regions that control REM sleep. AIM 1 will seek to detect abnormally phosphorylated alpha- synuclein aggregates on targeted skin biopsy in a cohort of people with 5-HT RBD and matched controls (taking SSRIs but without RBD). Aim 2 will use ultra-high field MRI at 7T to examine the pontine region of the coeruleus/subcoeruleus complex for evidence of neurodegeneration as well as segment and parcellate REM sleep related neuronal structures. Aim 3 will test for speech deficits. While these aims are independent we suspect that the severity of autonomic, speech and cognitive deficits will correlate with loss of neuromelanin signal on MRI and pathology on skin biopsy.
The investigation is a longitudinal designed study to examine histopathology, neuroimaging changes and speech function from baseline (Time 1) to a follow-up after 30 months (Time 2). A total of 60 individuals, 30 with 5-HT RBD and 30 controls, will be recruited at Time 1, brought back at Time 2, and tested across all Aims at both study visits.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Serotonergic REM sleep behavior (5-HT RBD) participants
- •Inclusion Criteria:
- •Diagnosis of polysomnogram-confirmed RBD with history of dream enactment or clear dream enactment visualized on video from polysomnogram.
- •History of dream enactment began shortly after (less than 2 months) starting a serotonergic antidepressant medication. Control Participants
- •Inclusion Criteria:
- •Age (±3 years) and sex matched to participants with 5-HT RBD
- •On serotonergic medication for at least 6 months without history of dream enactment.
- •The following serotonergic medications will be included:
- •Citalopram, Escitalopram, Fluoxetine, Fluvoxamine, Paroxetine, and Sertraline
排除标准
- •Serotonergic REM sleep behavior (5-HT RBD) participants
- •Exclusion Criteria:
- •Younger than 18
- •Older than 75
- •Meet criteria for Parkinson's disease, dementia with Lewy bodies, Multiple System Atrophy, Pure Autonomic Failure, Alzheimer's disease, other diagnosed neurodegenerative disorder, or other known cause of RBD (e.g. narcolepsy)
- •Untreated obstructive sleep apnea, obesity hypoventilation, central sleep apnea or other sleep disordered breathing
- •History of dysarthria, aphasia or other condition which could interfere with speech assessment
- •Reduced capacity to consent
- •MRI exclusion criteria for 7T scans: presence of any metallic clip(s) or implantable medical devices (e.g., heart valve, aneurysm clip, coils or surgery, renal or aortic clips, shunts, stents or stent grafts, metal mesh/coil implants, neurostimulator, insulin pump, IVC filter, etc.).
- •History of allergic response to xylocaine or other local anesthesia
- •Pregnant women will be excluded due to unknown risk of MRI on developing fetus Control Participants
- •Exclusion Criteria: same exclusion criteria as 5-HT RBD group, plus the following:
- •History of dream enactment that may suggest RBD
- •Increased REM motor tone (REM atonia index > 0.10) on PSG suggestive of RBD
研究组 & 干预措施
Research participants
Adults under the age of 75; who do not meet criteria for Parkinson's disease, dementia with Lewy bodies, Alzheimer's disease, other diagnosed neurodegenerative disorder, or other known cause of RBD; and have a history of or currently use the SSRIs of interest.
干预措施: Ultra high field 7T MRI (Diagnostic Test)
Research participants
Adults under the age of 75; who do not meet criteria for Parkinson's disease, dementia with Lewy bodies, Alzheimer's disease, other diagnosed neurodegenerative disorder, or other known cause of RBD; and have a history of or currently use the SSRIs of interest.
干预措施: Skin biopsy (Diagnostic Test)
Research participants
Adults under the age of 75; who do not meet criteria for Parkinson's disease, dementia with Lewy bodies, Alzheimer's disease, other diagnosed neurodegenerative disorder, or other known cause of RBD; and have a history of or currently use the SSRIs of interest.
干预措施: Speech testing (Diagnostic Test)
结局指标
主要结局
Neuromelanin signal intensity in the Subcoeruleus/Coeruleus Complex
时间窗: time point 1 (baseline) and time point 2 (24 months, +/- 3 months)
Examination of the pontine region of the coeruleus/subcoeruleus complex for evidence of neurodegeneration as well as segment and parcellate REM sleep related neuronal structures.
Phosphorylated alpha synuclein deposits on skin biopsy
时间窗: time point 1 (baseline) and time point 2 (24 months, +/- 3 months)
Incidence (positive or negative) of phosphorylated alpha synuclein deposits. Indicating direct histopathological confirmation of underlying alpha-synuclein degeneration in 5-HT RBD in a cohort of people with 5-HT RBD and matched controls (taking SSRIs but without RBD).
Monopitch as measured by fundamental frequency variability.
时间窗: time point 1 (baseline) and time point 2 (24 months, +/- 3 months)
Participants' voice and speech quality will be examined for synucleinopathy syndrome. The focus on speech function is designed to detect subtle brainstem deficits prior to more overt manifestations of cortical dementia.
次要结局
- Speed of articulatory change as measured by F2 Transitions(time point 1 (baseline) and time point 2 (24 months, +/- 3 months))
- Subject-specific masks of all REM sleep-related pontine nuclei of interest, volume of Subcoeruleus/Coeruleus Complex.(time point 1 (baseline) and time point 2 (24 months, +/- 3 months))