Insomnia, Parkinson's Disease (PD)
Conditions
Keywords
Insomnia, Parkinson's disease, Daytime Function, effective, safety, dimdazenil
Brief summary
This study will use sleep parameters measured by polysomnography (PSG) as the primary means to evaluate the efficacy and safety of dimdazenil, a GABAA receptor partial agonist, in treating insomnia in Parkinson's disease patients.
Detailed description
This study will enroll a total of 50 Parkinson's disease patients with insomnia, aged ≥18 years. Eligible subjects who meet the inclusion and exclusion criteria and are judged by the investigator to be suitable for the study drug will receive dimdazenil capsules at a dose of 2.5 mg per night, with a total treatment duration of 14 days，taken orally immediately before bedtime as prescribed. The primary efficacy endpoint is the change from baseline in total sleep time (TST) measured by polysomnography (PSG) on the night of Day 14. Secondary endpoints include multiple objective and subjective sleep parameters derived from PSG and sleep diaries, daytime function assessed by validated scales, and Parkinson's disease symptoms.
Interventions
None listed
Sponsors
Second Affiliated Hospital of Soochow University
The Fourth Affiliated Hospital of Soochow University
Changshu Hospital of Traditional Chinese Medicine
The Second Affiliated Hospital of Jiaxing University
Study design
Observational model
CASE_ONLY
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Provide written informed consent voluntarily after full comprehension of the study. * Be aged ≥18 years, male or female. * Meet the diagnostic criteria for Parkinson's disease according to the Chinese Diagnostic Criteria for Parkinson's Disease (2016 Edition), with a modified Hoehn-Yahr stage ≤3. * Have insomnia symptoms \[reduced total sleep time (\<6.5 h) and/or sleep-onset latency \>30 min, and/or ≥2 nocturnal awakenings, early-morning awakening, or poor sleep quality\], occurring at least three times per week, accompanied by daytime dysfunction or daytime distress, with adequate opportunity for sleep yet difficulty initiating or maintaining sleep, and that cannot be fully explained by another sleep-wake disorder; and have satisfactory control of Parkinson's disease motor symptoms \[MDS-UPDRS Part III (ON state) score ≤30\]. * Be on a stable anti-Parkinsonian medication regimen, defined as no change in the type, dosage, or frequency of anti-Parkinsonian drugs for at least 4 weeks prior to enrollment, with no motor fluctuations or dyskinesia. * Have a clinical decision by the attending physician to initiate didazinin treatment per routine practice. * Be able to undergo polysomnography (PSG) monitoring. * Be conscious, capable of normal communication, and able to complete sleep diaries independently.
Exclusion criteria
* Have Parkinson-plus syndromes, secondary parkinsonism, or other non-idiopathic Parkinson's disease. * Have used benzodiazepine sedative-hypnotics within 7 days prior to enrollment. * Have other significant comorbidities, such as malignant tumors, or clinically significant impairment of cardiac, hepatic, or renal function. * Have severe obstructive sleep apnea (OSA), chronic obstructive pulmonary disease (COPD), respiratory insufficiency, or myasthenia gravis. * Have known hypersensitivity to any component of didazinin. * Have moderate-to-severe depression or anxiety, defined as a Hamilton Depression Rating Scale (HAMD) score ≥25 or a Hamilton Anxiety Rating Scale (HAMA) score ≥29. * Have a history of substance abuse (e.g., drug addiction or alcohol dependence). * Have a history of epilepsy, schizophrenia, bipolar disorder, developmental delay, or cognitive impairment. * Be pregnant or breastfeeding. * Be unwilling or unable to comply with scheduled follow-up visits. * Have any other condition that, in the investigator's judgment, would make the subject unsuitable for participation (e.g., anticipated inability to complete follow-up within 14 days, or concurrent use of other medications that may substantially interfere with sleep assessment and cannot be withdrawn).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in total sleep time (TST) measured by polysomnography (PSG) on the night of Day 14 of dimdazenil treatment | Baseline, Night 14 | Total sleep time (TST) is an objective sleep parameter derived from automatic recordings obtained via polysomnography (PSG). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in total sleep time (TST) measured by polysomnography (PSG) on the night of Day 1 of dimdazenil treatment | baseline, Night 1 | Total sleep time (TST) is an objective sleep parameter derived from automatic recordings obtained via polysomnography (PSG). |
| Change from baseline in Movement Disorder Society - Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS-III) motor examination score after 14 days of dimdazenil treatment | baseline, Day 14 | Movement Disorder Society - Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS-III) is the motor examination section of the MDS-UPDRS, used to assess the severity of motor symptoms in patients with Parkinson's disease. The MDS-UPDRS-III comprises 27 items across 14 categories, including facial expression, tremor, rigidity, bradykinesia, postural instability, and gait examination. Each item is scored on a 5-point Likert scale (ranging from 0 to 4), with a total score range of 0 to 108. Higher scores indicate more severe motor symptoms. |
| Change from baseline in latency to persistent sleep (LPS) measured by polysomnography (PSG) | baseline, Night 1，Night 14 | Latency to persistent sleep (LPS) is an objective sleep parameter derived from automatic recordings obtained via polysomnography (PSG), defined as the time from the start of PSG recording to the onset of non-rapid eye movement (NREM) sleep stage 1。 |
| Change from baseline in wake after sleep onset (WASO) measured by polysomnography (PSG) | baseline, Night 1，Night 14 | Wake after sleep onset（WASO） is an objective sleep parameter derived from automatic recordings obtained via polysomnography (PSG)。Polysomnography (PSG) is a medical device that comprehensively evaluates sleep quality by simultaneously recording more than 10 physiological parameters, including electroencephalography (EEG)。PSG is regarded as the "gold standard" for the diagnosis of sleep disorders. |
| Change from baseline in number of awakenings (NAW) measured by polysomnography (PSG) | baseline, Night 1，Night 14 | Number of awakenings (NAW) is an objective sleep parameter derived from automatic recordings obtained via polysomnography (PSG). |
| Change from baseline in sleep efficiency (SE) measured by polysomnography (PSG) | baseline, Night 1，Night 14 | Sleep efficiency (SE) is calculated from the total sleep time (TST) and total time in bed (TIB) recorded automatically by PSG, with the formula: SE = TST / TIB × 100%. Total sleep time (TST): The sum of the durations of all epochs scored as N1, N2, N3, and REM sleep in the PSG recording, excluding all epochs scored as "Wake". Total time in bed (TIB): The total duration from the start of PSG recording (when the subject goes to bed and prepares to sleep) to the end of recording (when the subject gets out of bed and leaves). |
| Change from baseline in subjective total sleep time (sTST) | baseline, Day 14 under the treatment of dimdazenil | subjective total sleep time (sTST) is recorded in sleep diary |
| Change from baseline in subjective sleep onset latency (sSL) | baseline, Day 14 under the treatment of dimdazenil | sSL is recorded in sleep diary |
| Change from baseline in subjective wake after sleep onset (sWASO) | baseline, Day 14 under the treatment of dimdazenil | sWASO is recorded in sleep diary |
| Change from baseline in subjective number of awakenings (sNAW) | baseline, Day 14 under the treatment of dimdazenil | sNAW is recorded in sleep diary |
| Change from baseline in subjective sleep efficiency (sSE) | baseline, Day 14 under the treatment of dimdazenil | Subjective sleep efficiency (sSE) is calculated from the subjective total sleep time (sTST) and total time in bed (TIB) recorded by the subject via a sleep diary, using the formula: sSE = sTST / TIB × 100%. Total time in bed (TIB): The total duration recorded by the subject from the time they go to bed and attempt to sleep to the time they get out of bed the next morning. Subjective total sleep time (sTST): The total sleep duration calculated by subtracting sleep latency (time to fall asleep) and wake after sleep onset (WASO) from the total time in bed (TIB). |
| Change from baseline in Insomnia Severity Index (ISI) total score | baseline, Day 14 under the treatment of dimdazenil | The Insomnia Severity Index (ISI) is a self-reported questionnaire used to assess the severity of insomnia in subjects. The ISI comprises 7 items grouped under 5 major domains. The total score is the sum of each individual item score, ranging from 0 to 28. Scores are interpreted as follows: 0-7: no clinically significant insomnia; 8-14: subthreshold insomnia; 15-21: clinical insomnia (moderate); 22-28: clinical insomnia (severe). |
| Changes from baseline in the Parkinson's Disease Sleep Scale (PDSS) total score and individual item scores after 14 days of dimdazenil treatment | baseline, Day 14 | The Parkinson's Disease Sleep Scale (PDSS) is a 15-item self-reported instrument specifically designed to evaluate nocturnal sleep disturbances and daytime functioning in patients with Parkinson's disease. Each item is scored from 0 to 10 (0 = extremely severe symptoms, 10 = no symptoms), with a total score ranging from 0 to 150. Higher scores indicate better sleep quality. |
| PSG-recorded sleep time duration in NREM sleep stages 1（N1） | baseline, Night 1, Night 14 | Sleep time duration in Non-rapid eye movement(NREM) sleep stages 1（N1） is derived from automatic recordings obtained via polysomnography (PSG). |
| PSG-recorded sleep time duration in NREM sleep stages 2（N2） | baseline, Night 1, Night 14 | Sleep time duration in Non-rapid eye movement(NREM) sleep stages 2（N2） is derived from automatic recordings obtained via polysomnography (PSG). |
| PSG-recorded sleep time duration in NREM sleep stages 3（N3） | baseline, Night 1, Night 14 | Sleep time duration in Non-rapid eye movement(NREM) sleep stages 3（N3） is derived from automatic recordings obtained via polysomnography (PSG). |
| PSG-recorded sleep time duration in REM sleep | baseline, Night 1, Night 14 | Sleep time duration in rapid eye movement(REM) sleep is derived from automatic recordings obtained via polysomnography (PSG). |
| PSG-recorded sleep latency for N1 sleep | baseline, Night 1, Night 14 | Sleep latency for N1 sleep is derived from automatic recordings obtained via polysomnography (PSG). N1 latency is defined as the time from sleep onset to the first occurrence of N1 sleep. |
| PSG-recorded sleep latency for N2 sleep | baseline, Night 1, Night 14 | Sleep latency for N2 sleep is derived from automatic recordings obtained via polysomnography (PSG). N2 latency is defined as the time from sleep onset to the first occurrence of N2 sleep. |
| PSG-recorded sleep latency for N3 sleep | baseline, Night 1, Night 14 | "Sleep latency for N3 sleep is derived from automatic recordings obtained via polysomnography (PSG). N3 latency is defined as the time from sleep onset to the first occurrence of N3 sleep. " |
| PSG-recorded sleep latency for REM sleep | baseline, Night 1, Night 14 | Sleep latency for rapid eye movement(REM) sleep is derived from automatic recordings obtained via polysomnography (PSG). REM latency is defined as the time from sleep onset to the first occurrence of REM sleep. |
| the percentage of total sleep time accounted for by N1 sleep | baseline, Night 1, Night 14 | The percentage of total sleep time spent in N1 sleep (N1%) was calculated using the following formula: N1% = (N1 duration / TST) × 100%, where N1 duration was defined as the total duration of epochs scored as N1 sleep on PSG, and TST was defined as the total duration of all sleep epochs (N1 + N2 + N3 + REM). |
| the percentage of total sleep time accounted for by N2 sleep | baseline, Night 1, Night 14 | The percentage of total sleep time spent in N2 sleep (N2%) was calculated using the following formula: N2% = (N2 duration / TST) × 100%, where N2 duration was defined as the total duration of epochs scored as N2 sleep on PSG, and TST was defined as the total duration of all sleep epochs (N1 + N2 + N3 + REM). |
| the percentage of total sleep time accounted for by N3 sleep | baseline, Night 1, Night 14 | The percentage of total sleep time spent in N3 sleep (N3%) was calculated using the following formula: N3% = (N3 duration / TST) × 100%, where N3 duration was defined as the total duration of epochs scored as N3 sleep on PSG, and TST was defined as the total duration of all sleep epochs (N1 + N2 + N3 + REM). |
| the percentage of total sleep time accounted for by REM sleep | baseline, Night 1, Night 14 | The percentage of total sleep time spent in REM sleep (REM%) was calculated using the following formula: REM% = (REM duration / TST) × 100%, where REM duration was defined as the total duration of epochs scored as REM sleep on PSG, and TST was defined as the total duration of all sleep epochs (N1 + N2 + N3 + REM). |
| Fatigue assessment after 14 days of dimdazenil treatment | baseline, Day 14 | Fatigue will be assessed using the Flinders Fatigue Scale, and changes in scores from baseline will be evaluated after treatment. The Flinders Fatigue Scale is a self-reported instrument used to assess fatigue severity. It yields a total score ranging from 0 to 31, with higher scores reflecting more severe fatigue. |
| Daytime sleepiness assessment after 14 days of dimdazenil treatment | baseline, Day 14 | Daytime sleepiness assessment will be assessed using the Epworth Sleepiness Scale (ESS), and changes in scores from baseline will be evaluated after treatment. The Epworth Sleepiness Scale is a self-reported instrument used to assess daytime sleepiness severity. It yields a total score ranging from 0 to 24, with higher scores reflecting more severe sleepiness. |
| Attention and working memory assessment after 14 days of dimdazenil treatment | baseline, Day 14 | Attention and working memory assessment will be assessed using the Digit Symbol Substitution Test (DSST), and changes in scores from baseline will be evaluated after treatment. The Digit Symbol Substitution Test (DSST) is a self-reported instrument used to assess attention and working memory. In the Digit Symbol Substitution Test (DSST), the total number of symbols completed and the total number of errors made by the subjects will be recorded. A higher number of symbols completed and a lower number of errors indicate better attention and working memory function. |
| Cognitive function assessment after 14 days of dimdazenil treatment | baseline, Day 14 | Cognitive function assessment will be assessed using the Trail Making Test-A (TMT-A), and changes in scores from baseline will be evaluated after treatment. The Trail Making Test-A (TMT-A) is a self-reported instrument used to assess cognitive function. In the Trail Making Test-A (TMT-A), the completion time and number of errors are recorded. Shorter completion times and fewer errors indicate better cognitive function. |
| Incidence of adverse events during dimdazenil treatment | From date of signing the informed consent until the date of the end of study visit or early withdrawal, assessed up to 14 days | — |
Contacts
CONTACTXy Cheng
Outcome results
None listed