Remote Ischemic Conditioning for Sleep Disturbances and Other Non-motor Symptoms in Parkinson's Disease

Official title

Remote Ischemic Conditioning for Sleep Disturbances and Other Non-motor Symptoms in Parkinson's Disease: a Randomized, Single-blind, Sham-controlled Clinical Study

Overview

This single-center, randomized, single-blind, sham-controlled clinical trial aims to evaluate whether remote ischemic conditioning (RIC) can improve sleep disturbances and other non-motor symptoms in patients with Parkinson's disease (PD). Forty-eight PD patients with insomnia will be randomly assigned in a 1:1 ratio to receive either active RIC (cuff inflation to high pressure) or sham RIC (cuff inflation to low pressure) for 7 consecutive days, in addition to their standard antiparkinsonian medications. Subjective sleep scales, sleep diaries, validated rating scales for motor and non-motor symptoms, and overnight polysomnography will be used to assess treatment effects at baseline, after the 7-day intervention, and during short-term follow-up. The study will also explore potential mechanisms of RIC by combining EEG, functional MRI, retinal optical coherence tomography, and blood biomarkers.

Detailed description

Parkinson's disease (PD) is a common neurodegenerative disorder characterized not only by motor symptoms, but also by a wide spectrum of non-motor symptoms. Sleep disturbances, including insomnia and fragmented sleep, are highly prevalent in PD and markedly impair quality of life, yet current pharmacological therapies have limited efficacy and may cause adverse effects. Remote ischemic conditioning (RIC) is a non-invasive intervention induced by repeated brief episodes of limb ischemia and reperfusion using an inflatable cuff. Experimental and clinical studies suggest that RIC can modulate immune responses, humoral mediators, neural activity and circadian rhythms. Based on these observations, we hypothesize that RIC may improve sleep disturbances and other non-motor symptoms in PD.

In this study, 48 PD patients with insomnia will be recruited from the outpatient clinics and inpatient wards of Nanjing Brain Hospital. Eligible participants will be randomized (1:1) to an active RIC group or a sham RIC group on top of stable antiparkinsonian medications. Each participant will undergo two nights of polysomnography (one adaptation night and one baseline recording), comprehensive clinical assessments, EEG, retinal optical coherence tomography (OCT) and functional MRI (fMRI) before the intervention. RIC or sham RIC will then be performed twice daily for 7 consecutive days. After completion of the 7-day intervention, polysomnography, EEG, fMRI, OCT, clinical rating scales and blood sampling will be repeated. A further clinical and neurophysiological assessment will be conducted approximately 21 days after the end of RIC to evaluate the persistence of treatment effects. The primary objective is to determine whether RIC improves subjective and objective sleep parameters in PD patients with insomnia. Secondary objectives include assessing changes in other non-motor symptoms, motor symptoms, cognition, mood, autonomic function, quality of life and exploratory imaging and blood biomarkers.

Interventions

• Device Remote ischemic conditioning device
  An automated upper-limb cuff device is applied to one arm to induce brief episodes of limb ischemia and reperfusion. In the active RIC group, the cuff is inflated to a high pressure (approximately 200 mmHg) sufficient to occlude arterial blood flow, and then deflated repeatedly according to a pre-set program recommended by the manufacturer. RIC is performed twice daily for 7 consecutive days.
• Device Sham remote ischemic conditioning
  The same device and procedure are used as in the active RIC group, but the cuff is inflated only to a low pressure (approximately 60 mmHg) that does not occlude arterial blood flow. Sham RIC is performed twice daily for 7 consecutive days.

Primary outcome measures

• Change in Parkinson's Disease Sleep Scale-2 (PDSS-2) total score [Time frame: From baseline to 7 days after the start of RIC]

Secondary outcome measures (2)

• Change in Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) total score (0-260 points; higher scores indicate worse motor and non-motor symptoms). [Time frame: Baseline to 7 days after RIC]
• Change in Montreal Cognitive Assessment (MoCA) total score (0-30 points; higher scores indicate better cognitive function). [Time frame: Baseline to 7 days after RIC]

Eligibility criteria

Inclusion criteria

• Diagnosis of Parkinson's disease according to the Movement Disorder Society (MDS) clinical diagnostic criteria.
• Age between 50 and 70 years.
• Disease duration ≤ 5 years.
• Hoehn and Yahr stage I-III in the "on" state.
• Presence of insomnia that meets the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria and clinically significant sleep complaints (for example, Parkinson's Disease Sleep Scale-2 \[PDSS-2\] total score ≥ 18 points).
• On a stable regimen of antiparkinsonian medications for at least 4 weeks prior to enrollment, with no expected dose changes during the study period.
• Able to understand the study procedures and provide written informed consent (or consent provided by a legally authorized representative when appropriate).

Exclusion criteria

• Secondary insomnia due to other severe medical conditions (e.g., uncontrolled cardiopulmonary, hepatic, renal, or endocrine diseases).
• Current psychotic symptoms or severe anxiety or depression (e.g., Hamilton Anxiety Scale score ≥ 14 or Hamilton Depression Scale score ≥ 17).
• Other primary sleep disorders such as moderate-to-severe obstructive sleep apnea, restless legs syndrome, periodic limb movement disorder, or rapid eye movement sleep behavior disorder that require specific treatment.
• History of significant cerebrovascular disease, brain tumor, central nervous system infection, or other neurological disorders that may interfere with sleep or study assessments.
• Contraindications to remote ischemic conditioning (RIC), including severe peripheral arterial disease of the upper limbs, local soft tissue infection or damage at the cuff site, subclavian artery thrombosis, malignant hypertension, severe cardiac disease, active bleeding disorders, or other conditions judged unsafe by the investigator.
• Contraindications to MRI or EEG examinations (e.g., pacemaker, severe claustrophobia, metallic implants incompatible with MRI).
• Participation in another interventional clinical trial within the past 3 months.
• Inability to comply with the study procedures or follow-up visits, as judged by the investigator.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

China · 1 center

• The Affiliated Brain Hospital of Nanjing Medical University, 264 Guangzhou Road — Nanjing

Identifiers

NCT: NCT07299240 · 2024-KY088-02

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗