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

Parkinson Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04006925
• Other study ID #: 47852
• Status: Completed
• Phase: Phase 4
• Start date: September 10, 2019
• Est. completion date: February 1, 2022

Study information

• Verified date: April 2023
• Source: Stanford University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: February 1, 2022
• Est. primary completion date: February 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Mental Disorders
• Parkinson Disease
• REM Sleep Behavior Disorder

Intervention

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").

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.

Locations

Country	Name	City	State
United States	Stanford University	Palo Alto	California

Sponsors (2)

Lead Sponsor	Collaborator
Stanford University	Jazz Pharmaceuticals

Country where clinical trial is conducted

United States, 

References & Publications (3)

Liebenthal J, Valerio J, Ruoff C, Mahowald M. A Case of Rapid Eye Movement Sleep Behavior Disorder in Parkinson Disease Treated With Sodium Oxybate. JAMA Neurol. 2016 Jan;73(1):126-7. doi: 10.1001/jamaneurol.2015.2904. No abstract available. — View Citation

Moghadam KK, Pizza F, Primavera A, Ferri R, Plazzi G. Sodium oxybate for idiopathic REM sleep behavior disorder: a report on two patients. Sleep Med. 2017 Apr;32:16-21. doi: 10.1016/j.sleep.2016.04.014. Epub 2016 Jun 7. — View Citation

Shneerson JM. Successful treatment of REM sleep behavior disorder with sodium oxybate. Clin Neuropharmacol. 2009 May-Jun;32(3):158-9. doi: 10.1097/WNF.0b013e318193e394. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of RBD Episodes in One Month (Per Patient RBD Log)	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)
Primary	Number of Severe of RBD Episodes in One Month (Per Patient RBD Log)	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): 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...; 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; 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	Number of Responders According to the CGI Efficacy Scale (CGI-E)	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).
Secondary	Number of Responders According to the CGI Improvement Scale (CGI-I)	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).
Secondary	Epworth Sleepiness Scale (ESS) Score	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
Secondary	RBD Episode Severity and Frequency During REM Sleep by Quantitative Video-PSG (Polysomnography) Analysis Per 10 Minutes of REM Sleep	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)
Secondary	Change in Ambulatory Measures of Movements During Sleep Using Actigraphy	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)