Parkinson Disease
Conditions
Keywords
excessive daytime somnolence, Parkinson disease, sleep disturbance
Brief summary
This clinical trial is designed to evaluate the safety and potential efficacy of Xyrem for the treatment of excessive daytime sleepiness (EDS) and nocturnal sleep disturbance in patients with mild to moderate Parkinson's Disease (PD).
Detailed description
Inclusion required an Epworth Sleepiness Scale (ESS) score greater than 10 and any subjective nocturnal sleep concern, usually insomnia. An acclimation and screening polysomnogram was performed to exclude subjects with sleepdisordered breathing. The following evening, subjects underwent another polysomnogram, followed by an evaluation with the Unified Parkinson Disease Rating Scale (UPDRS) while practically defined off (off) PD medications, ESS (primary efficacy point), Pittsburgh Sleep Quality Inventory, and Fatigue Severity Scale. Subjects then started sodium oxybate therapy, which was titrated from 3 to 9 g per night in split doses (at bedtime and 4 hours later) across 6 weeks, and returned for subjective sleep assessments. They then returned at 12 weeks after initiating therapy for a third polysomnogram, an offmedication UPDRS evaluation, and subjective sleep assessments. Data are expressed as mean (SD).
Interventions
DRUGsodium oxybate
4.5 to 9.0 grams per night
Sponsors
Jazz Pharmaceuticals
Baylor College of Medicine
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
30 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Male or female with a diagnosis of idiopathic PD. * Age between 30 and 75, inclusive. -Hoehn & Yahr Stage 1.5 - 4.0 in the practically defined medication OFF. - * History \> 2 months of excessive daytime sleepiness confirmed at baseline/screening by an Epworth Sleepiness Scale score of \> 10. * History \> 2 months of nocturnal sleep disturbances consisting of insomnia, fragmented sleep and/or non-restorative sleep. * Folstein Mini-Mental State Exam score of \> 24. * Birth control for sexually active women of childbearing potential (e.g. abstinence, hormonal contraception, barrier method, intrauterine device). * Evidence of a personally signed and dated informed consent form document indicating that the subject (or a legally acceptable representative) has been informed of all pertinent aspects of the trial. * Subjects who are willing and able to comply with scheduled visits, treatment plan, and other study procedures. * Stable dose of medications, defined as no change in dose or regimen of medications for at least 3 months prior to Screen Visit.
Exclusion criteria
* Known idiopathic sleep pathology: sleep apnea and narcolepsy. * Serious co-morbid disease --Atypical parkinsonism (e.g., Parkinson plus syndrome, secondary Parkinson's syndrome). --Significant neurological symptoms not accounted for by PD. --Significant psychiatric symptoms or dementia. * Sexually active women of childbearing potential without adequate form of birth control. * Pregnancy or lactation. * Mini-mental status examination of \< 25. * Participation in another clinical trial of another investigational agent or device within the previous 60 days. * Current abuse of alcohol or drugs. * Active or prior malignancy other than cutaneous basal cell carcinoma or in situ carcinoma of the uterine cervix. * Known hypersensitivity to sodium oxybate or other constituents of the product. * Any medical conditions that are contraindications to the use of sodium oxybate or significant hepatic impairment. * Patients being treated with sedative hypnotic agents or other central nervous system (CNS) depressants. * Subjects taking warfarin. * Patients with succinic semialdehyde dehydrogenase deficiency. * Subjects who, in the opinion of the investigator, are not able to comply with the requirements of the study. * Any other condition that, in the investigator's opinion, would cause a significant hazard to the subject.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sleep and Fatigue | 8 weeks | Sleep and Fatigue was measured using the following scales before and after sodium oxybate therapy Scales used to measure sleep and fatigue: Epworth Sleepiness Scale (ESS) where score ranges from 0-24 where 0 = no sleep problems and 24 = excessive sleep problems that should seek medical attention; Fatigue Severity Scale (FSS) where the score ranges from 9-36 where 9 = no fatigue and 36 = severe fatigue; Pittsburgh Sleep Quality Inventory (PSQI) where the score ranges from 0-21 where any score greater than 5 indicates a great sleep disturbance; 36-Item Short Form Health Survey (SF-36) where the score ranges 0-100 where 0 = the worst health status and 100 = the best health status. \* Findings are reported for 28 subjects. The Full Range values reported reflect the measured minimum and maximum values. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Polysomnography (PSG) | 8 weeks | Polysomnography, also called a sleep study, is a comprehensive test used to diagnose sleep disorders. The minimum score would be 0, the maximum score would be 30. A score of 0 - 4 = normal sleep, a score of 5 - 14 = a mild level of sleep disturbance, a score of 15 - 30 is moderate level of sleep disturbance and a score of 30 is severe sleep disturbance. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment Group Active treatment group with Xyrem in PD | 30 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 3 |
Baseline characteristics
| Characteristic | Treatment Group |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 10 Participants |
| Age, Categorical Between 18 and 65 years | 20 Participants |
| Region of Enrollment United States | 30 participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 30 |
| other Total, other adverse events | 9 / 30 |
| serious Total, serious adverse events | 0 / 30 |
Outcome results
Primary
Sleep and Fatigue
Sleep and Fatigue was measured using the following scales before and after sodium oxybate therapy Scales used to measure sleep and fatigue: Epworth Sleepiness Scale (ESS) where score ranges from 0-24 where 0 = no sleep problems and 24 = excessive sleep problems that should seek medical attention; Fatigue Severity Scale (FSS) where the score ranges from 9-36 where 9 = no fatigue and 36 = severe fatigue; Pittsburgh Sleep Quality Inventory (PSQI) where the score ranges from 0-21 where any score greater than 5 indicates a great sleep disturbance; 36-Item Short Form Health Survey (SF-36) where the score ranges 0-100 where 0 = the worst health status and 100 = the best health status. \* Findings are reported for 28 subjects. The Full Range values reported reflect the measured minimum and maximum values.
Time frame: 8 weeks
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Trial of Xyrem for Excessive Daytime Sleepiness and Sleep Disturbance | Sleep and Fatigue | Before Sodium Oxybate Therapy (baseline) ESS | 15.6 units on a scale |
| Trial of Xyrem for Excessive Daytime Sleepiness and Sleep Disturbance | Sleep and Fatigue | After Sodium Oxybate Therapy (8 weeks) ESS | 9.0 units on a scale |
| Trial of Xyrem for Excessive Daytime Sleepiness and Sleep Disturbance | Sleep and Fatigue | Before Sodium Oxybate Therapy (baseline) PSQI | 10.9 units on a scale |
| Trial of Xyrem for Excessive Daytime Sleepiness and Sleep Disturbance | Sleep and Fatigue | After Sodium Oxybate Therapy (8 weeks) PSQI | 6.6 units on a scale |
| Trial of Xyrem for Excessive Daytime Sleepiness and Sleep Disturbance | Sleep and Fatigue | Before Sodium Oxybate Therapy (baseline) FSS | 32.9 units on a scale |
| Trial of Xyrem for Excessive Daytime Sleepiness and Sleep Disturbance | Sleep and Fatigue | After Sodium Oxybate Therapy (8 weeks) FSS | 26.3 units on a scale |
| Trial of Xyrem for Excessive Daytime Sleepiness and Sleep Disturbance | Sleep and Fatigue | Before Sodium Oxybate Therapy (baseline) SF-36 | 95.7 units on a scale |
| Trial of Xyrem for Excessive Daytime Sleepiness and Sleep Disturbance | Sleep and Fatigue | After Sodium Oxybate Therapy (8 weeks) SF-36 | 92.3 units on a scale |
Secondary
Polysomnography (PSG)
Polysomnography, also called a sleep study, is a comprehensive test used to diagnose sleep disorders. The minimum score would be 0, the maximum score would be 30. A score of 0 - 4 = normal sleep, a score of 5 - 14 = a mild level of sleep disturbance, a score of 15 - 30 is moderate level of sleep disturbance and a score of 30 is severe sleep disturbance.
Time frame: 8 weeks
Population: A polysomnography was done before and after therapy as a secondary measure. The results are below.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Trial of Xyrem for Excessive Daytime Sleepiness and Sleep Disturbance | Polysomnography (PSG) | Mean Polysomnography Before Therapy | 7 units on a scale |
| Trial of Xyrem for Excessive Daytime Sleepiness and Sleep Disturbance | Polysomnography (PSG) | Mean Polysomnography After Therapy | 13 units on a scale |