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

NCT04006925 | Completed Phase 4 Results FDA Drug

• 1 other identifier: 47852
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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).

Conditions

REM Sleep Behavior Disorder; Parkinson Disease

Keywords

sodium oxybate

Outcome Measures

Primary Outcomes (2)

• 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)

• 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): 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 Outcomes (5)

• Number of Responders According to the CGI Efficacy Scale (CGI-E)

  Assessed at week 12 (end of treatment period).

• Number of Responders According to the CGI Improvement Scale (CGI-I)

  Assessed at week 12 (end of treatment period).

• Epworth Sleepiness Scale (ESS) Score

  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

  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

  Assessed for 28 days at baseline and during last month of treatment (total treatment period of up to 12 weeks)

Study Arms (2)

Sodium Oxybate (SXB) arm

ACTIVE COMPARATOR

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

Drug: Sodium Oxybate

Placebo (PBO) arm

PLACEBO COMPARATOR

Placebo will be dispensed to the participants.

Other: Placebo

Interventions

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").

Sodium Oxybate (SXB) arm

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.

Placebo (PBO) arm

Eligibility Criteria

• Age: 40 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Stanford University: lead
• Jazz Pharmaceuticals: collaborator

Study Sites (1)

Stanford University

Palo Alto, California, 94306, United States

Location

Related Publications (4)

• 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.

  PMID: 19483483 BACKGROUND

• 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.

  PMID: 26595534 BACKGROUND

• 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.

  PMID: 28366329 BACKGROUND

• During EH, Hernandez B, Miglis MG, Sum-Ping O, Hekmat A, Cahuas A, Ekelmans A, Yoshino F, Mignot E, Kushida CA. Sodium oxybate in treatment-resistant rapid-eye-movement sleep behavior disorder. Sleep. 2023 Aug 14;46(8):zsad103. doi: 10.1093/sleep/zsad103.

  PMID: 37052688 DERIVED

MeSH Terms

Conditions

REM Sleep Behavior Disorder; Parkinson Disease

Interventions

Sodium Oxybate

Condition Hierarchy (Ancestors)

REM Sleep Parasomnias; Parasomnias; Sleep Wake Disorders; Nervous System Diseases; Mental Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Hydroxybutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Hydroxy Acids

Results Point of Contact

• Title: Emmanuel During
• Organization: Stanford University

Emmanuel.During@mountsinai.org

212-844-8888

Study Officials

• Emmanuel During, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized, double-blind, placebo-controlled trial

Study Record Dates

• First Submitted: June 27, 2019
• First Posted: July 5, 2019
• Study Start: September 10, 2019
• Primary Completion: February 1, 2022
• Study Completion: February 1, 2022
• Last Updated: May 10, 2023
• Results First Posted: May 10, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)