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

GHB

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).

Intervention / Treatment

Randomized, double-blind, placebo-controlled trial
  • Sodium Oxybate (DRUG)
    Sodium Oxybate will be titrated up weekly by 1.5g nightly dose increments from an initial 4.5g total nightly dose (which could be given in two unequal doses if needed, or one single dose no greater than 4.5g) to an optimal individual dose based on clinical response on RBD symptoms and tolerance, to a maximum nightly dose of 9g ("flexible dose" period lasting up to 8 weeks). The optimal dose will then be continued for at least 4 weeks ("stable dose").
  • Placebo (OTHER)
    Placebo will be similar in appearance, smell and flavor to the subjects, so that the investigators and participants will be unable to distinguish it from sodium oxybate.

Condition or Disease

  • REM Sleep Behavior Disorder
  • Parkinson Disease

Phase

  • Phase 4

    • Study Design

    Study type: INTERVENTIONAL
    Status: Completed
    Study results: No Results Available
    Age: 40 Years to 85 Years
    Enrollment: 24 (ACTUAL)
    Funded by: Other|Industry
    Allocation: Randomized
    Primary Purpose: Treatment

    Masking

    QUADRUPLE:
    • Participant
    • Care Provider
    • Investigator
    • Outcomes Assessor

    Clinical Trial Dates

    Start date: Sep 10, 2019 ACTUAL
    Primary Completion: Feb 01, 2022 ACTUAL
    Completion Date: Feb 01, 2022 ACTUAL
    Study First Posted: Jul 05, 2019 ACTUAL
    Results First Posted: May 10, 2023 ACTUAL
    Last Updated: Apr 18, 2023

    Sponsors / Collaborators

    Lead Sponsor: Stanford University
    Lead sponsor is responsible party
    Responsible Party: N/A

    Location

    Palo Alto, California, USA

    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.

    Participant Groups

    • Sodium Oxybate (SXB) will be dispensed to the participants.

    • Placebo will be dispensed to the participants.

    Eligibility Criteria

    Sex: All
    Minimum Age: 40
    Maximum Age: 85
    Age Groups: Adult / Older Adult
    Healthy Volunteers: Yes

    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

    Primary Outcomes

    • Patients record any episode of dream enactment, such as talking, shouting, kicking, or punching, etc.

    • 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 Outcomes

    • 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."

    • 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) 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.

    • 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.

    • Measure of "activity score" using in-home 4-week actigraphy

    More Details

    NCT Number: NCT04006925
    Other IDs: 47852
    Study URL: https://clinicaltrials.gov/study/NCT04006925
    Last updated: Sep 29, 2023