A Phase II, Prospective, Randomized, Double-blind, Crossover Placebo-controlled Study of the Symptomatic Effects of Nocturnal Sodium Oxybate in Parkinson's Disease
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Christian Baumann
- Enrollment
- 16
- Locations
- 1
- Primary Endpoint
- effect on night-time breathing
Study Overview
Brief Summary
Sleep wake disturbance is a common problem in Parkinson's disease patients and so far the therapeutic possibilities for symptomatic relief are limited. Small, open-label studies indicate that the use of Xyrem (gamma-hydroxybutyrate) might be of benefit in this situation.
This study is intended to show a beneficial effect of the study medication in a randomized cross-over trial, that fulfills strict scientific criteria.
Detailed Description
Background and Rationale
Non-motor symptoms as excessive daytime sleepiness (EDS) are markedly impairing quality of life in Parkinson's Disease (PD) patients. Beside the disturbing character of these symptoms, EDS for example is also linked to a decrease in cognitive abilities or mood, i.e. depression [1,2]. The most prominent cause for EDS is a disruption of nocturnal sleep [3]. Furthermore disrupted nocturnal sleep is also likely influencing quality of life of partners or caregivers. This aspect of non-motor symptoms has not been investigated in detail so far. In conclusion, we are firmly convinced that the improvement of nocturnal sleep in PD patients is a promising potential strategy to reduce several symptoms and adverse events in PD patients and their partners or caregivers. Moreover, sleep modulation is a recently introduced approach of potential neuroprotective strategies, e.g. since sleep deprivation was linked with neurodegenerative processes in the brain [4,5].
It has already been shown in a recent study that the nocturnal application of sodium oxybate in PD patients is not only improving nocturnal sleep quality, but is accompanied by a reduction in EDS [6]. There were, however, significant methodological limitations to this study, since it was a single-arm, open-label, uncontrolled study.
In summary, the nocturnal application of sodium oxybate seems to be a promising treatment for PD patients, but methodologically correct evidence is still lacking.
Investigational Product
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 90 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Moderate to severe Parkinson's disease (Hoehn and Yahr II/III) diagnosis according to international criteria [14],
- •History of disturbed nocturnal sleep and presence of EDS (ESS >10 points),
- •Doses of dopaminergic and other PD treatment must have been stable for at least 14 days prior to the screening visit,
- •Negative pregnancy test prior to inclusion (except in women who are surgically sterilized/hysterectomized or post-menopausal for longer than 2 years),
- •Patients are capable of giving informed consent,
- •Signed Informed Consent after being informed.
Exclusion Criteria
- •Atypical Parkinson disorder, Parkinson's disease without response to levodopa,
- •AHI >15 or oxygen saturation consistently below 90% on baseline polysomnography
- •diagnosis of sleep apnoea-syndrome or COPD
- •Severe dementia (MoCA<22),
- •Moderate to severe depression (HADS>15).
- •Contraindications to the class of drugs under study, e.g. known hypersensitivity or allergy to class of drugs or the investigational product,
- •Regular use of CNS depressant substances (opioids, barbiturates) as well as melatonin and other sleep-inducing substances,
- •Other clinically significant concomitant disease states (e.g., renal insufficiency (creatinin > 120 resp. GFR <40ml/min), hepatic dysfunction (GPT > 100U/l), severe cardiovascular disease, etc),
- •Known or suspected non-compliance, substance or alcohol abuse (i.e. > 0.5 l wine or 1 l beer per day),
- •Homeless persons,
- •Women who are pregnant or breast feeding,
- •Intention to become pregnant during the course of the study,
- •Lack of safe contraception, defined as:
- •Female patients 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 patients who are surgically sterilized/hysterectomized or post-menopausal for longer than 2 years are not considered as being of child bearing potential.
- •Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, etc. of the patient,
- •Participation in another study with investigational drug within the 30 days preceding and during the present study,
- •Previous enrolment into the current study,
- •Enrolment of the investigator, his/her family members, employees and other dependent persons,
Arms & Interventions
Sodium Oxybate
Treatment (500mg Natrii oxybas/ml) will be administered every day at night time for 6 weeks each orally by the patient itself. If necessary, the investigator will make sure that a relative or caregiver is able to assist in daily treatment administration. The dosage starts at 3g per night and is adapted in steps of 1.5g during visits and telephone screenings and always noted in the "medication log-book". The maximal dosage is 9g per night.
Intervention: Sodium Oxybate (Drug)
Placebo
Treatment will be administered every day at night time for 6 weeks each orally by the patient itself. If necessary, the investigator will make sure that a relative or caregiver is able to assist in daily treatment administration. As with the active compound, placebo will be given with a starting dose of 3g per night and is adapted in steps of 1.5g during visits and telephone screenings and always noted in the "medication log-book". The maximal dosage is 9g per night.
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
effect on night-time breathing
Time Frame: after 6 weeks of treatment
AHI (apnoea/hypopnoea) score on polysomnography
Objective excessive daytime sleepiness
Time Frame: after 6 weeks of treatment
mean latencies in the MSLT (multiple sleep latency test)
Secondary Outcomes
- Vigilance(after 6 weeks of treatment)
- Objective quality of nocturnal sleep including breathing indices(after 6 weeks of treatment)
- Overall quality of life(after 6 weeks of treatment)
- Motor function(after 6 weeks of treatment)
- Subjective quality of nocturnal sleep(after 6 weeks of treatment)
- Quality of life for caregivers(after 6 weeks of treatment)
- Sleep wake rhythm(after 6 weeks of treatment)
- Cognition(after 6 weeks of treatment)
- Subjective Daytime sleepiness(after 6 weeks of treatment)
- Mood(after 6 weeks of treatment)
- Impulse control(after 6 weeks of treatment)
Investigators
Christian Baumann
Professor dr. med.
University of Zurich