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

April 18, 2023 updated by: Stanford University

Sodium Oxybate in Treatment-Resistant REM Sleep Behavior Disorder (RBD): A Randomized Placebo-Controlled Trial

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

24

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Palo Alto, California, United States, 94306
        • Stanford University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

40 years to 85 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Sodium Oxybate (SXB) arm
Sodium Oxybate (SXB) will be dispensed to the participants.
Drug: Sodium Oxybate
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 Comparator: Placebo (PBO) arm
Placebo will be dispensed to the participants.
Other: Placebo
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of RBD Episodes in One Month (Per Patient RBD Log)
Time Frame: 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.
Assessed for 28 days at baseline and during last month of treatment (total treatment period of up to 12 weeks)
Number of Severe of RBD Episodes in One Month (Per Patient RBD Log)
Time Frame: 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.
Assessed for 28 days at baseline and during last month of treatment (total treatment period of up to 12 weeks)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Responders According to the CGI Efficacy Scale (CGI-E)
Time Frame: 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."
Assessed at week 12 (end of treatment period).
Number of Responders According to the CGI Improvement Scale (CGI-I)
Time Frame: 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."
Assessed at week 12 (end of treatment period).
Epworth Sleepiness Scale (ESS) Score
Time Frame: 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.
Assessed at baseline and week 12
RBD Episode Severity and Frequency During REM Sleep by Quantitative Video-PSG (Polysomnography) Analysis Per 10 Minutes of REM Sleep
Time Frame: 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.
Assessed at baseline and week 12 (average approximately 8 hours to assess at each time point)
Change in Ambulatory Measures of Movements During Sleep Using Actigraphy
Time Frame: 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
Assessed for 28 days at baseline and during last month of treatment (total treatment period of up to 12 weeks)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Stanford University

Collaborators

Jazz Pharmaceuticals

Investigators

  • Principal Investigator: Emmanuel During, MD, Stanford University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 10, 2019

Primary Completion (Actual)

February 1, 2022

Study Completion (Actual)

February 1, 2022

Study Registration Dates

First Submitted

June 27, 2019

First Submitted That Met QC Criteria

July 1, 2019

First Posted (Actual)

July 5, 2019

Study Record Updates

Last Update Posted (Actual)

May 10, 2023

Last Update Submitted That Met QC Criteria

April 18, 2023

Last Verified

April 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 47852

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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