Effects of Lemborexant on Motor-sleep Comorbidity in Parkinson's Disease

Official title

Study for the Dual Orexin Receptor Antagonist Lemborexant in Improving Motor-Sleep Comorbidity in Parkinson's Disease

Overview

The aim of this study is to explore the effects of the dual orexin receptor antagonist Lemborexant on improving motor and sleep comorbidity in patients with Parkinson's disease. This study will provide clinical evidence for the application of dual orexin receptor antagonists in the treatment of Parkinson's Disease.

Detailed description

Parkinson's disease (PD) is the most common movement disorder. Its core motor symptoms include bradykinesia, resting tremor, muscle rigidity, and postural instability. Furthermore, patients frequently experience severe non-motor symptoms, such as sleep disorders and mood/affective disturbances. Among these, sleep disorders, especially insomnia, are one of the most prevalent non-motor symptoms. They are often overlooked in clinical management. The axons of central orexin neurons project extensively throughout the brain, encompassing key regions such as motor control centers and sleep-wake regulation centers. During the pathological process of PD, dysfunctional orexin neurons may contribute to the disruption of both motor and sleep functions by modulating these target areas.

By recruiting PD patients with comorbid motor and insomnia symptoms, the investigators will investigate the efficacy of Lemborexant in treating both motor and sleep disturbances in PD patients. With its advantages of target specificity, established safety, and a lower side-effect profile compared to traditional hypnotics, Lemborexant holds promise as a novel therapeutic intervention for Parkinson's disease. This research may offer new possibilities for expanding clinical treatment strategies for PD. Participants will take 5 mg medication (or placebo) each night for 28 days and be asked to come for 4 times study visits (Baseline, at the end of the 7-day post-treatment, at the end of the 28-day post-treatment, 7-day follow up).

The major experiment contents include:

1. To evaluate the effect of oral Lemborexant on Parkinson's disease motor symptoms in participants (using the Unified Parkinson's Disease Rating Scale, UPDRS); 2. To evaluate the effect of oral Lemborexant on the sleep quality of participants (using the Parkinson's Disease Sleep Scale (PDSS), the Insomnia Severity Index (ISI), the Pittsburgh Sleep Quality Index (PSQI)).

Interventions

• Drug Lemborexant
  Participants will receive oral Lemborexant (5 mg/day) nightly approximately 5-30 minutes before going to bed for 28 consecutive days.
• Drug placebo
  Participants will receive a matching placebo nightly approximately 5-30 minutes before going to bed for 28 consecutive days.

Primary outcome measures

• Changes in the scores of the Parkinson's Disease Sleep Scale (PDSS) [Time frame: Baseline, at the end of the 7-day post-treatment, at the end of the 28-day post-treatment, 7-day follow up.]
• Changes in the scores of Part III of the Unified Parkinson's Disease Rating Scale (UPDRS) [Time frame: Baseline, at the end of the 7-day post-treatment, at the end of the 28-day post-treatment, 7-day follow up.]

Secondary outcome measures (3)

• Changes in the scores of Part II of the Unified Parkinson's Disease Rating Scale (UPDRS) [Time frame: Baseline, at the end of the 7-day post-treatment, at the end of the 28-day post-treatment, 7-day follow up.]
• Changes in the scores of the Insomnia Severity Index (ISI) [Time frame: Baseline, at the end of the 7-day post-treatment, at the end of the 28-day post-treatment, 7-day follow up.]
• Changes in the scores of the Pittsburgh Sleep Quality Index (PSQI) [Time frame: Baseline, at the end of the 7-day post-treatment, at the end of the 28-day post-treatment, 7-day follow up.]

Eligibility criteria

Inclusion criteria

• 1\. Aged 50 years or older;
• 2\. Diagnosed with idiopathic Parkinson's disease according to the Movement Disorder Society Clinical Diagnostic Criteria for Parkinson's Disease (2015), with a Hoehn \& Yahr stage of 1 to 4;
• 3\. Disease duration of ≥ 2 years since diagnosis, clinically stable, and able to comply with the research assessments and interventions;
• 4\. Diagnosis of insomnia disorder meeting the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), with an Insomnia Severity Index (ISI) score of ≥ 15;
• 5\. Stable medication regimen for at least 4 weeks prior to the study;
• 6\. Signed informed consent form, with the participant or their legal guardian able to understand and willing to participate in this study.

Exclusion criteria

• 1\. History of or diagnosis with a severe psychiatric disorder, such as depression, anxiety disorders, schizophrenia spectrum disorders, or bipolar disorder;
• 2\. Presence of a clinically defined neurological disorder (assessed via self-report), including but not limited to: any condition potentially associated with increased intracranial pressure, space-occupying brain lesions, history of stroke, transient ischemic attack within the past 2 years, cerebral aneurysm, dementia, or multiple sclerosis;
• 3\. Severe cognitive impairment (Mini-Mental State Examination (MMSE) score below 24) or inability to complete questionnaires independently;
• 4\. Chronic obstructive pulmonary disease (COPD) or any lifelong history of sleep-related breathing disorders, such as sleep apnea;
• 5\. Excessive daytime sleepiness, defined as self-reported daily daytime napping ≥ 1 hour per day on ≥ 3 days per week;
• 6\. Regular caffeine consumption;
• 7\. Use of any orexin receptor related medication within the past 3 months.
• 8\. Previous history of cataplexy or known reduced orexin levels;
• 9\. Inability to read or understand Chinese;
• 10\. Use of other sleep-promoting medications within the past 3 months.

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

Triple blind

Primary purpose

Treatment

Study locations

China · 1 center

• Zhongnan hospital — Wuhan

Identifiers

NCT: NCT07384429 · 2025401

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗