Trial Outcomes & Findings for Treatment of REM Sleep Behavior Disorder (RBD) With Sodium Oxybate (NCT NCT04006925)

NCT ID: NCT04006925

Last Updated: 2023-05-10

Results Overview

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

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 24 participants
• Primary outcome timeframe: Assessed for 28 days at baseline and during last month of treatment (total treatment period of up to 12 weeks)
• Results posted on: 2023-05-10

Participant Flow

Participant milestones

Measure	Sodium Oxybate (SXB) Arm For each participant, Sodium Oxybate (SXB) starting at a 4.5g total nightly dose then titrated up weekly by 1.5g increments over 8 weeks to establish their optimal individualized dose (based on their clinical response on RBD symptoms and tolerance). Participant then receive their optimal dose for at least 4 weeks.	Placebo (PBO) Arm Placebo similar in appearance, smell and flavor so that it is indistinguishable from sodium oxybate.
Overall Study STARTED	12	12
Overall Study COMPLETED	10	12
Overall Study NOT COMPLETED	2	0

Reasons for withdrawal

Measure	Sodium Oxybate (SXB) Arm For each participant, Sodium Oxybate (SXB) starting at a 4.5g total nightly dose then titrated up weekly by 1.5g increments over 8 weeks to establish their optimal individualized dose (based on their clinical response on RBD symptoms and tolerance). Participant then receive their optimal dose for at least 4 weeks.	Placebo (PBO) Arm Placebo similar in appearance, smell and flavor so that it is indistinguishable from sodium oxybate.
Overall Study Side effects	2	0

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Sodium Oxybate (SXB) Arm n=12 Participants For each participant, Sodium Oxybate (SXB) starting at a 4.5g total nightly dose then titrated up weekly by 1.5g increments over 8 weeks to establish their optimal individualized dose (based on their clinical response on RBD symptoms and tolerance). Participant then receive their optimal dose for at least 4 weeks.	Placebo (PBO) Arm n=12 Participants Placebo similar in appearance, smell and flavor so that it is indistinguishable from sodium oxybate.	Total n=24 Participants Total of all reporting groups
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	66.1 years STANDARD_DEVIATION 8.2 • n=5 Participants	65.4 years STANDARD_DEVIATION 7.3 • n=7 Participants	65.8 years STANDARD_DEVIATION 7.6 • n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	9 Participants n=7 Participants	18 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	12 Participants n=5 Participants	12 Participants n=7 Participants	24 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	12 Participants n=5 Participants	12 Participants n=7 Participants	24 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	12 Participants n=5 Participants	12 Participants n=7 Participants	24 Participants n=5 Participants
Body Mass Index (BMI)	24.4 kg/m^2 STANDARD_DEVIATION 4.7 • n=5 Participants	27.0 kg/m^2 STANDARD_DEVIATION 7.6 • n=7 Participants	25.7 kg/m^2 STANDARD_DEVIATION 6.3 • n=5 Participants
RBD Symptom Duration	11.2 years STANDARD_DEVIATION 6.9 • n=5 Participants	8.4 years STANDARD_DEVIATION 4.3 • n=7 Participants	9.8 years STANDARD_DEVIATION 5.8 • n=5 Participants
History of Injuries	10 Participants n=5 Participants	12 Participants n=7 Participants	22 Participants n=5 Participants
Parkinson disease	6 Participants n=5 Participants	6 Participants n=7 Participants	12 Participants n=5 Participants
Sleep Apnea	2 Participants n=5 Participants	5 Participants n=7 Participants	7 Participants n=5 Participants
Insomnia	2 Participants n=5 Participants	5 Participants n=7 Participants	7 Participants n=5 Participants
Current Treatment Antidepressant	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Current Treatment Clonazepam	5 Participants n=5 Participants	4 Participants n=7 Participants	9 Participants n=5 Participants
Current Treatment Melatonin	8 Participants n=5 Participants	6 Participants n=7 Participants	14 Participants n=5 Participants
Current Treatment Cholinergic	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Current Treatment Dopaminergic	6 Participants n=5 Participants	4 Participants n=7 Participants	10 Participants n=5 Participants

PRIMARY outcome

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

Population: Participants with data at each time point are included in the analysis

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

Outcome measures

Measure	Placebo (PBO) Arm n=12 Participants Placebo similar in appearance, smell and flavor so that it is indistinguishable from sodium oxybate.	Sodium Oxybate (SXB) Arm n=12 Participants For each participant, Sodium Oxybate (SXB) starting at a 4.5g total nightly dose then titrated up weekly by 1.5g increments over 8 weeks to establish their optimal individualized dose (based on their clinical response on RBD symptoms and tolerance). Participant then receive their optimal dose for at least 4 weeks.
Number of RBD Episodes in One Month (Per Patient RBD Log) Baseline	35.0 episodes Interval 28.5 to 45.5	37.5 episodes Interval 27.5 to 48.5
Number of RBD Episodes in One Month (Per Patient RBD Log) Final dose	25.5 episodes Interval 14.5 to 46.0	23.5 episodes Interval 6.0 to 47.0

PRIMARY outcome

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

Population: Participants with data at each time point are included in the analysis

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.

Outcome measures

Measure	Placebo (PBO) Arm n=12 Participants Placebo similar in appearance, smell and flavor so that it is indistinguishable from sodium oxybate.	Sodium Oxybate (SXB) Arm n=12 Participants For each participant, Sodium Oxybate (SXB) starting at a 4.5g total nightly dose then titrated up weekly by 1.5g increments over 8 weeks to establish their optimal individualized dose (based on their clinical response on RBD symptoms and tolerance). Participant then receive their optimal dose for at least 4 weeks.
Number of Severe of RBD Episodes in One Month (Per Patient RBD Log) Baseline	1.5 episodes Interval 0.0 to 3.5	1.5 episodes Interval 0.5 to 4.0
Number of Severe of RBD Episodes in One Month (Per Patient RBD Log) Final dose	1.0 episodes Interval 0.0 to 2.5	0.5 episodes Interval 0.0 to 1.0

SECONDARY outcome

Timeframe: 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."

Outcome measures

Measure	Placebo (PBO) Arm n=12 Participants Placebo similar in appearance, smell and flavor so that it is indistinguishable from sodium oxybate.	Sodium Oxybate (SXB) Arm n=12 Participants For each participant, Sodium Oxybate (SXB) starting at a 4.5g total nightly dose then titrated up weekly by 1.5g increments over 8 weeks to establish their optimal individualized dose (based on their clinical response on RBD symptoms and tolerance). Participant then receive their optimal dose for at least 4 weeks.
Number of Responders According to the CGI Efficacy Scale (CGI-E)	6 Participants	10 Participants

SECONDARY outcome

Timeframe: 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."

Outcome measures

Measure	Placebo (PBO) Arm n=12 Participants Placebo similar in appearance, smell and flavor so that it is indistinguishable from sodium oxybate.	Sodium Oxybate (SXB) Arm n=12 Participants For each participant, Sodium Oxybate (SXB) starting at a 4.5g total nightly dose then titrated up weekly by 1.5g increments over 8 weeks to establish their optimal individualized dose (based on their clinical response on RBD symptoms and tolerance). Participant then receive their optimal dose for at least 4 weeks.
Number of Responders According to the CGI Improvement Scale (CGI-I)	7 Participants	10 Participants

SECONDARY outcome

Timeframe: Assessed at baseline and week 12

Population: Participants with data at each time point are included in the analysis

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.

Outcome measures

Measure	Placebo (PBO) Arm n=12 Participants Placebo similar in appearance, smell and flavor so that it is indistinguishable from sodium oxybate.	Sodium Oxybate (SXB) Arm n=12 Participants For each participant, Sodium Oxybate (SXB) starting at a 4.5g total nightly dose then titrated up weekly by 1.5g increments over 8 weeks to establish their optimal individualized dose (based on their clinical response on RBD symptoms and tolerance). Participant then receive their optimal dose for at least 4 weeks.
Epworth Sleepiness Scale (ESS) Score Baseline	9.5 score on a scale Interval 4.0 to 10.0	8.0 score on a scale Interval 5.5 to 10.0
Epworth Sleepiness Scale (ESS) Score Final dose	7.5 score on a scale Interval 5.0 to 10.5	5.0 score on a scale Interval 4.0 to 8.0

SECONDARY outcome

Timeframe: Assessed at baseline and week 12 (average approximately 8 hours to assess at each time point)

Population: Participants with data available at the respective time points are presented.

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.

Outcome measures

Measure	Placebo (PBO) Arm n=10 Participants Placebo similar in appearance, smell and flavor so that it is indistinguishable from sodium oxybate.	Sodium Oxybate (SXB) Arm n=8 Participants For each participant, Sodium Oxybate (SXB) starting at a 4.5g total nightly dose then titrated up weekly by 1.5g increments over 8 weeks to establish their optimal individualized dose (based on their clinical response on RBD symptoms and tolerance). Participant then receive their optimal dose for at least 4 weeks.
RBD Episode Severity and Frequency During REM Sleep by Quantitative Video-PSG (Polysomnography) Analysis Per 10 Minutes of REM Sleep Baseline	10.1 episodes*severity per 10 minutes of REM Standard Deviation 8.4	13.2 episodes*severity per 10 minutes of REM Standard Deviation 12.3
RBD Episode Severity and Frequency During REM Sleep by Quantitative Video-PSG (Polysomnography) Analysis Per 10 Minutes of REM Sleep Final dose	10.5 episodes*severity per 10 minutes of REM Standard Deviation 10.0	7.2 episodes*severity per 10 minutes of REM Standard Deviation 7.4

SECONDARY outcome

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

Population: Analysis was not possible because the data that were collected were corrupted and uninterpretable.

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

Outcome measures

Outcome data not reported

Adverse Events

Sodium Oxybate (SXB) Arm

Serious events: 5 serious events

Other events: 7 other events

Deaths: 0 deaths

Placebo (PBO) Arm

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Measure	Sodium Oxybate (SXB) Arm n=12 participants at risk For each participant, Sodium Oxybate (SXB) starting at a 4.5g total nightly dose then titrated up weekly by 1.5g increments over 8 weeks to establish their optimal individualized dose (based on their clinical response on RBD symptoms and tolerance). Participant then receive their optimal dose for at least 4 weeks.	Placebo (PBO) Arm n=12 participants at risk Placebo similar in appearance, smell and flavor so that it is indistinguishable from sodium oxybate.
Musculoskeletal and connective tissue disorders Myoclonus episode	8.3% 1/12 • Up to 12 weeks	0.00% 0/12 • Up to 12 weeks
Psychiatric disorders Sleep terror	8.3% 1/12 • Up to 12 weeks	0.00% 0/12 • Up to 12 weeks
Psychiatric disorders Suicidal ideation	8.3% 1/12 • Up to 12 weeks	0.00% 0/12 • Up to 12 weeks
Psychiatric disorders Anxiety	8.3% 1/12 • Up to 12 weeks	0.00% 0/12 • Up to 12 weeks
Nervous system disorders Dizziness	8.3% 1/12 • Up to 12 weeks	0.00% 0/12 • Up to 12 weeks

Other adverse events

Measure	Sodium Oxybate (SXB) Arm n=12 participants at risk For each participant, Sodium Oxybate (SXB) starting at a 4.5g total nightly dose then titrated up weekly by 1.5g increments over 8 weeks to establish their optimal individualized dose (based on their clinical response on RBD symptoms and tolerance). Participant then receive their optimal dose for at least 4 weeks.	Placebo (PBO) Arm n=12 participants at risk Placebo similar in appearance, smell and flavor so that it is indistinguishable from sodium oxybate.
Psychiatric disorders Anxiety	8.3% 1/12 • Up to 12 weeks	0.00% 0/12 • Up to 12 weeks
General disorders Asthenia	8.3% 1/12 • Up to 12 weeks	0.00% 0/12 • Up to 12 weeks
Psychiatric disorders Auditory hallucination	8.3% 1/12 • Up to 12 weeks	0.00% 0/12 • Up to 12 weeks
General disorders Brain fog	16.7% 2/12 • Up to 12 weeks	0.00% 0/12 • Up to 12 weeks
Renal and urinary disorders Enuresis	8.3% 1/12 • Up to 12 weeks	0.00% 0/12 • Up to 12 weeks
Gastrointestinal disorders Gastrointestinal discomfort	8.3% 1/12 • Up to 12 weeks	0.00% 0/12 • Up to 12 weeks
Nervous system disorders Headache	8.3% 1/12 • Up to 12 weeks	0.00% 0/12 • Up to 12 weeks
General disorders Hot flashes	8.3% 1/12 • Up to 12 weeks	8.3% 1/12 • Up to 12 weeks
Musculoskeletal and connective tissue disorders Myalgia	8.3% 1/12 • Up to 12 weeks	0.00% 0/12 • Up to 12 weeks
Gastrointestinal disorders Nausea	8.3% 1/12 • Up to 12 weeks	0.00% 0/12 • Up to 12 weeks
General disorders Sensation of being "wired"	8.3% 1/12 • Up to 12 weeks	0.00% 0/12 • Up to 12 weeks
Nervous system disorders Tremor	8.3% 1/12 • Up to 12 weeks	0.00% 0/12 • Up to 12 weeks
Psychiatric disorders Anorexia	16.7% 2/12 • Up to 12 weeks	0.00% 0/12 • Up to 12 weeks
General disorders Catathrenia	8.3% 1/12 • Up to 12 weeks	0.00% 0/12 • Up to 12 weeks
General disorders Increased sweating	16.7% 2/12 • Up to 12 weeks	0.00% 0/12 • Up to 12 weeks
Psychiatric disorders Insomnia	0.00% 0/12 • Up to 12 weeks	8.3% 1/12 • Up to 12 weeks
Gastrointestinal disorders Dysgeusia	8.3% 1/12 • Up to 12 weeks	0.00% 0/12 • Up to 12 weeks

Additional Information

Emmanuel During

Stanford University

Phone: 212-844-8888

Email: Emmanuel.During@mountsinai.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place