Non-pharmacological Enhancement of Deep Sleep With Auditory Stimulation Versus Sham in People With Parkinson's Disease and Mild Cognitive Impairment Receiving Cognitive Training: A Double-blind Randomized Trial (PD-CogT-Sleep)
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Additive Effect of PTAS on Cognitive Improvements (Executive Performance) Through Digital Cognitive Training in PD-MCI
研究概览
简要总结
People with Parkinson's disease are at higher risk of cognitive decline, and current treatments cannot fully prevent this. This study explores non-drug ways to support brain function.
Intervention: Participants will complete a 5-week cognitive training program at home ("brain fitness"). In addition, they will use a sleep device at night that plays soft sounds to improve deep sleep; Half of the participants will actually receive these sounds (auditory stimulation), while the other half will receive a sham (placebo) version - neither the participants nor the researchers will know the group assignment.
Assessments will take place before and after the intervention, and again three months later, including one overnight stay at University Hospital Zurich per assessment.
The goal is to find out whether improving deep sleep can boost the benefits of cognitive training and help slow cognitive decline in Parkinson's disease.
详细描述
Parkinson's disease (PD) is a progressive neurodegenerative disorder associated not only with motor symptoms (such as tremor, slowness of movement, and rigidity), but also with a broad range of non-motor symptoms. Sleep disturbances are common, and many individuals with PD develop cognitive impairment, ranging from mild cognitive impairment (MCI) to dementia. For early cognitive impairment in PD, pharmacological treatment options are limited, and there are currently no established therapies that reliably prevent further cognitive decline. There is therefore a clear need to develop and evaluate non-pharmacological interventions that can support cognitive functioning in this population.
Cognitive training (CogT) is a structured, exercise-based intervention targeting cognitive domains such as attention, memory, and executive functions (e.g., planning and coordination of actions). Evidence supports the efficacy of CogT in PD and in older adults; however, response to training varies considerably between individuals. Sleep-particularly deep sleep-has been proposed as an important factor influencing learning and cognitive performance. Deep sleep is implicated in processes relevant to memory consolidation and daytime cognition. Because sleep disturbances are frequent in PD, impaired sleep may represent a barrier to achieving optimal benefits from CogT.
This study evaluates whether enhancing deep sleep using phase-targeted auditory stimulation (PTAS) can improve the effectiveness of CogT in people with PD and MCI. PTAS is a non-pharmacological method that delivers soft, non-arousing sounds during sleep with the aim of supporting deep sleep. The intervention is administered using a wearable headband device developed at the University of Zurich and ETH Zurich. The device is designed for home use and can be worn during sleep in the participant's own bed. The technology has been used in previous research in younger and older healthy individuals as well as in people with PD, with no relevant side effects reported, and has demonstrated beneficial effects on measures of deep sleep.
Study Design
This is a double-blind, randomized, sham-controlled trial. After eligibility screening, participants are randomly assigned to one of two groups:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •clinical diagnosis of PD along the MDS criteria (Postuma et al., 2015)
- •MCI according to the MDS criteria, level I (Litvan et al., 2012):
- •- cognitive decline: Gradual decline, in the context of established PD, in cognitive ability reported by either the patient or informant, or observed by the clinician, AND
- •- MoCA ≤ 26 and ≥ 18 (Hoops et al., 2009)
- •stable home situation (e.g. long-term place to live) that allows for reliable application of intervention for the duration of the study
- •ability to apply the sleep intervention for the duration of study, either alone or with assistance of a co-habitant if needed
- •ability to apply the CogT intervention for the duration of study
- •sufficient German language comprehension to follow the study procedures and answer all questions related to the study outcomes
- •dosing of dopaminergic and other PD treatment must have been stable for at least 14 days prior to the intervention period and will be expected to remain stable until the end of the study.
排除标准
- •Diagnosis/Comorbidities:
- •clinical diagnosis of dementia (cognitive impairment sufficient to interfere with independence in everyday activities, i.e. "major neurocognitive disorder", DSM-5)
- •known presence of neurologic (other than PD) or psychiatric disorder
- •Parkinsonism without response to levodopa; atypical Parkinsonian syndromes as assessed from medical history and clinical examination
- •severe medical conditions (for example, renal insufficiency, liver failure, or congestive heart failure) as assessed in the semi-structured screening interview
- •regular use of benzodiazepines and other central nervous system (CNS)-depressant substances as assessed in the semi-structured screening interview
- •known or suspected drug- or medication abuse as assessed in the semi-structured screening interview
- •substance or alcohol abuse (i.e. > 0.5 l wine or 1 l beer per day) as assessed in the semi-structured screening interview
- •Sleep disorders that could interfere with the sleep intervention:
- •obstructive sleep apnea with apnea-hypopnea index (AHI)>15, apnea-related NREM sleep fragmentation, and indication for treatment (in turn, primarily REM-related sleep apnea, not requiring specific treatment may be considered eligible); or use of continuous positive airway pressure (CPAP)
- •Restless Legs Syndrome
- •frequent (i.e. weekly) Non-REM sleep parasomnia (Sleep disorders typically associated with PD will not lead to exclusion, i.e. REM sleep behavior disorder, insomnia, nocturnal PD symptoms.)
- •inability to hear the tones produced by the sleep headband (TOSOO Axora device)
- •non-responder to PTAS during screening (PTAS does not evoke a discernable auditory evoked potential AEP)
- •skin disorders/problems/allergies in face/ear area that could worsen with electrode application
- •known or suspected non-compliance
- •Cognition & informed consent:
- •inability to follow the procedures of the study, e.g. due to language problems, cognitive deficits
- •failure to give informed consent
- •Other studies:
- •participation in another study with investigational interventions within 30 days (PTAS) or 1 year (CogT) preceding and during the present study
- •previous enrolment in the current study
- •enrolment of the investigator, his/her family members, employees and other dependent persons
- •Special events / behavior with impact on circadian rhythm, sleep, or cognition:
- •shift work (work during the night)
- •travelling more than 2 time zones in the last month before intervention starts or during intervention (start of intervention will be adapted to fit with this criteria)
- •planned medical intervention of substantial relevance, e.g. surgery, during intervention (routine assessments, e.g. check-ups will be allowed)
- •women who are pregnant or breastfeeding,
- •intention to become pregnant during the course of the study,
- •lack of safe contraception, defined as: Female participants of childbearing potential, not using and not willing to continue using a medically reliable method of contraception for the entire study duration, such as oral, injectable, or implantable contraceptives, or intrauterine contraceptive devices, or who are not using any other method considered sufficiently reliable by the investigator in individual cases. Please note that female participants who are surgically sterilized/hysterectomized or post-menopausal for longer than 1 year are not considered as being of child bearing potential.
研究组 & 干预措施
PTAS + Digital Cognitive Training
Participants in this arm will receive active phase-targeted auditory stimulation during sleep. In addition, all participants will complete an identical digital, home-based cognitive training program following the same study schedule and procedures.
干预措施: Phase-Targeted Auditory Stimulation (PTAS) (Device)
PTAS + Digital Cognitive Training
Participants in this arm will receive active phase-targeted auditory stimulation during sleep. In addition, all participants will complete an identical digital, home-based cognitive training program following the same study schedule and procedures.
干预措施: Digital Cognitive Training (CogT) (Other)
Sham-PTAS + Digital Cognitive Training
Participants in this control arm will receive sham PTAS using the same device and identical procedures as in the active condition, but without inducing slow-wave enhancement. All participants will also complete the same digital, home-based cognitive training program.
干预措施: Digital Cognitive Training (CogT) (Other)
结局指标
主要结局
Additive Effect of PTAS on Cognitive Improvements (Executive Performance) Through Digital Cognitive Training in PD-MCI
时间窗: Assessed at baseline (pre-intervention), after 5 weeks (post-intervention), and 3-month follow-up.
The primary outcome is the change in executive functioning between baseline and follow-up assessments, compared between the CogT+PTAS and CogT+Sham groups. Executive performance will be measured using an equally weighted composite domain score, calculated as the mean of multiple demographically adjusted, standardized z-scores from neuropsychological tests within the executive domain. This composite score captures the multidimensional nature of executive functions and reduces random measurement error.
次要结局
- Additive Effect of PTAS on Cognitive Improvements (Global Cognitive Performance) Through Digital Cognitive Training in PD-MCI(Assessed at baseline (pre-intervention), after 5 weeks (post-intervention), and 3-month follow-up.)
- Additive Effect of PTAS on Cognitive Improvements (Attention and Working Memory) Through Digital Cognitive Training in PD-MCI(Assessed at baseline (pre-intervention), after 5 weeks (post-intervention), and 3-month follow-up.)
- Additive Effect of PTAS on Cognitive Improvements (Visuo-Cognitive Performance) Through Digital Cognitive Training in PD-MCI(Assessed at baseline (pre-intervention), after 5 weeks (post-intervention), and 3-month follow-up.)
- Additive Effect of PTAS on Cognitive Improvements (Language Performance) Through Digital Cognitive Training in PD-MCI(Assessed at baseline (pre-intervention), after 5 weeks (post-intervention), and 3-month follow-up.)
- Effect of PTAS on Blood Neurofilament Light Chain (NfL) Levels in PD-MCI(Assessed at baseline (pre-intervention), after 5 weeks (post-intervention), and 3-month follow-up.)