Treatment of REM Sleep Behavior Disorder (RBD) With Sodium Oxybate

Phase 4

Completed

Conditions: Parkinson Disease
REM Sleep Behavior Disorder

Interventions: Other: Placebo
Drug: Sodium Oxybate

Registration Number: NCT04006925

Lead Sponsor: Stanford University

Brief Summary: This study is the first clinical trial using sodium oxybate for the treatment of REM sleep behavior disorder (RBD). Sodium oxybate is a drug approved by FDA for the treatment of narcolepsy which has been used "off label" to treat patients with severe RBD. This drug has shown to be effective and well tolerated in patients with RBD (Shneerson, 2009; Liebenthal, 2016; Moghadam, 2017).

Detailed Description: Rapid eye movement sleep behavior disorder (RBD) is a condition resulting in violent dream-enactment during sleep which affects millions of individuals in the United States, however therapies for RBD are limited and cause significant side effects. As a result, despite using a combination of drugs, a large number of patients with RBD continue to act out violent dreams causing severe self-injuries or injuries to their bed partners. Prior studies and our experience have shown that sodium oxybate can be effective in these cases of treatment-resistant RBD. This study would therefore evaluate the efficacy and tolerance of sodium oxybate in this patient population.

This study is an 8-week trial comparing sodium oxybate versus placebo randomly assigned to patients with treatment-resistant RBD, i.e. individuals who have insufficiently responded or tolerated melatonin and clonazepam. The study uses a double-blind design (participants, staff, and investigators will not know which drug between active drug and placebo is given to participants), and will measure treatment efficacy based on patients, partners and clinicians report, and objective outcomes based on in-home actigraphy and in-lab polysomnography before and after intervention.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 24

Inclusion Criteria

40-85 years old
With or without Parkinson's disease
Experiencing RBD episodes on average at least 2x/week or 8x/month
Able to report RBD episodes themselves or via a partner witness

Exclusion Criteria

History of falls during ambulation in the last 6 months despite adequate neurologic treatment
Requirement of an ambulatory device at home
Inadequately treated symptomatic orthostatic hypotension
BMI > 35
Untreated or uncontrolled OSA (4%AHI>15)
Cognitive impairment resulting in inability to comply with treatment instructions
Pregnancy

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo (PBO) arm	Placebo	Placebo will be dispensed to the participants.
Sodium Oxybate (SXB) arm	Sodium Oxybate	Sodium Oxybate (SXB) will be dispensed to the participants.

Primary Outcome Measures

Name	Time	Method
Number of RBD Episodes in One Month (Per Patient RBD Log)	Assessed for 28 days at baseline and during last month of treatment (total treatment period of up to 12 weeks)	Patients record any episode of dream enactment, such as talking, shouting, kicking, or punching, etc.
Number of Severe of RBD Episodes in One Month (Per Patient RBD Log)	Assessed for 28 days at baseline and during last month of treatment (total treatment period of up to 12 weeks)	Patients record any episode of dream enactment, such as talking, shouting, kicking, or punching, etc. Severity is scored from 1 to 3 (1: least severe, 3 most severe): 1. non injurious behaviors: facial expressions, non-aggressive vocalizations (mumbling, gentle talking, casual conversation, singing, laughing...), twitches, gentle shaking, non-aggressive movements of fingers, arms or legs...; 2. potentially injurious: punching, kicking, arm flailing or thrashing around, at least one limb or head out of bed, sitting up in bed, crawling, attempting to stand up or leave bed, near falls, cursing, screaming, shouting, yelling, or any behavior requiring bed partner to wake up participant; 3. injurious: any contact with bed partner (hitting or grabbing), wall or furniture, any fall or leaving bed (doving out, walking, jumping). The number of injurious (severe) episodes is reported.

Secondary Outcome Measures

Name	Time	Method
Number of Responders According to the CGI Efficacy Scale (CGI-E)	Assessed at week 12 (end of treatment period).	Clinical Global Impression-Efficacy index (CGI-E) is a 4x4 rating scale that assesses the therapeutic effect (Marked, Moderate, Minimal, Unchanged or worse) of treatment medication and associated side effects (none, do not significantly interfere with patient's functioning, significantly interfere with patient's functioning, Outweigh therapeutic effect). Therapeutic effect: Marked and Side effects: None is the best. Therapeutic effect: Unchanged or worse and Side effects: outweigh therapeutic effect is the worst. Each combination of an estimated therapeutic effect and side effect is assigned a score from 1-16, 1 being the best, 16 being the worst. Participants scoring below 4 were considered to be "responders."
Number of Responders According to the CGI Improvement Scale (CGI-I)	Assessed at week 12 (end of treatment period).	Clinical Global Impression-Improvement scale (CGI-I) is a 7-point scale that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention and rated as: 1. Very much improved, 2. Much improved, 3. Minimally improved, 4. No change, 5. Minimally worse, 6. Much worse, 7. Very much worse. 1 is the best and 7 is the worst. Participants scoring below 4 were considered to be "responders."
Epworth Sleepiness Scale (ESS) Score	Assessed at baseline and week 12	Epworth Sleepiness Scale (ESS) is a scale to assess patients' general level of sleepiness. Patients choose the most appropriate number (0=would never doze, 1=slight chance of dozing, 2=moderate chance of dozing, 3=high chance of dozing) for the each situation: Sitting and reading, Watching TV, Sitting and inactive in a public place, As a passenger in a car for an hour, Lying down to rest in the afternoon, Sitting and talking to someone, Sitting quietly after a lunch, While stopped for a few minutes in the traffic in a car. 0-10: Normal range, 10-12: Borderline, 12-24: Abnormal. Participants recorded their scores for 28 days at baseline and during the 28 days leading up to week 12; scores were then averaged to calculate the score for each time point per participant, and then the median for all participants is reported.
RBD Episode Severity and Frequency During REM Sleep by Quantitative Video-PSG (Polysomnography) Analysis Per 10 Minutes of REM Sleep	Assessed at baseline and week 12 (average approximately 8 hours to assess at each time point)	The average number of dream-enactment episodes (resulting in motor behaviors, or movements) weighted for severity. Frequency and severity were calculated as the sum of RBD episodes (frequency) times severity (mild = 1; moderate = 5, severe = 10) occurring over one night's sleep, then averaged to calculate the number of episodes per 10 minutes of REM sleep.
Change in Ambulatory Measures of Movements During Sleep Using Actigraphy	Assessed for 28 days at baseline and during last month of treatment (total treatment period of up to 12 weeks)	Measure of "activity score" using in-home 4-week actigraphy