Evaluation of the Efficacy of Sodium Oxybate (Xyrem®) in Treatment of Post-traumatic Narcolepsy and Post-traumatic Hypersomnia

NCT03626727 | Withdrawn Early Phase 1 FDA Drug

• 1 other identifier: 2017-P-002884
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The study evaluates whether the use of Sodium Oxybate (Xyrem®) in TBI patients will be effective in reducing symptoms of post traumatic narcolepsy and post traumatic hypersomnia.

Conditions

Hypersomnia; Narcolepsy; Traumatic Brain Injury

Keywords

Excessive Daytime Sleepiness; Prolonged sleep; Traumatic Brain Injury

Outcome Measures

Primary Outcomes (4)

• Change in Subjective Daytime Sleepiness

  Change in subjective daytime sleepiness assessed through a daily questionnaire about frequency and duration of daytime naps, frequency of sleep attacks.

  Data collected on Day 1 (Baseline Visit) of the Intervention and at end of 1 week on the final dosage, which will be 2-5 weeks after the Baseline Visit.

• Change in Sleep Duration

  Change in sleep duration assessed by actigraphy-estimated total sleep time (TST).

  Data collected on Day 1 (Baseline Visit) of the Intervention and at end of 1 week on the final dosage, which will be 2-5 weeks after the Baseline Visit.

• Change in Clinical Condition

  Change in clinical condition as assessed by Clinical Global Impression (CGI) assessment. CGI assesses a clinician's view of a patient's global functioning before and after initiating medication. It is broken up into CGI-S (Severity) and CGI-I (Improvement). CGI-S is one question assesses how clinically ill a patient is at time of assessment. it is on a 1-7 scale with 1 being normal and 7 being among the most extremely ill patients. CGI-I looks at improvement in patients functioning once medication starts. it is also on a 1-7 scale with 1 being very much improved since initiation of treatment and 7 being very much worse.

  Data collected on Day 1 (Baseline Visit) of the Intervention and at end of 1 week on the final dosage, which will be 2-5 weeks after the Baseline Visit.

• Change in Subjective Daytime Sleepiness (ESS)

  Change in daytime sleepiness will be assessed through changes in Epworth Sleepiness Scale (ESS) scores. The ESS measures sleepiness of a participant. It is eight questions with a scale of 0 - 3 with 0 being no chance of dozing and 3 being high chance of dozing. The total score of eight questions is reported.

  Data collected on Day 1 (Baseline Visit) of the Intervention and at end of 1 week on the final dosage, which will be 2-5 weeks after the Baseline Visit.

Secondary Outcomes (8)

• Change in Nocturnal Sleep Quality (Frequency of nocturnal awakenings)

  Data collected on Day 1 (Baseline Visit) of the Intervention and at end of 1 week on the final dosage, which will be 2-5 weeks after the Baseline Visit.

• Change in Nocturnal Sleep Quality (Duration of nocturnal awakenings)

  Data collected on Day 1 (Baseline Visit) of the Intervention and at end of 1 week on the final dosage, which will be 2-5 weeks after the Baseline Visit.

• Change in Nocturnal Sleep Quality (Subjective amount of sleep)

  Data collected on Day 1 (Baseline Visit) of the Intervention and at end of 1 week on the final dosage, which will be 2-5 weeks after the Baseline Visit.

• Change in Nocturnal Sleep Quality (Frequency of sleep walking)

  Data collected on Day 1 (Baseline Visit) of the Intervention and at end of 1 week on the final dosage, which will be 2-5 weeks after the Baseline Visit.

• Change in Nocturnal Sleep Quality (Frequency of hypnagogic hallucinations)

  Data collected on Day 1 (Baseline Visit) of the Intervention and at end of 1 week on the final dosage, which will be 2-5 weeks after the Baseline Visit.

Study Arms (1)

Sodium Oxybate Oral Solution (Xyrem®)

EXPERIMENTAL

4.5g of oral solution Xyrem will be given as a starting dose. This will be titrated up weekly to the final treatment dose of 9.0g. Participants will be on this final dose for 8 weeks.

Drug: Sodium Oxybate Oral Solution [Xyrem]

Interventions

Sodium Oxybate Oral Solution [Xyrem] DRUG

Xyrem will be given to participants to determine if it is effective in treating post-traumatic narcolepsy and post-traumatic hypersomnia

Sodium Oxybate Oral Solution (Xyrem®)

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• History of first-ever primary TBI 12 or more months ago;
• Mild to severe TBI (GCS 3-15);
• Either a) or b):
• Presence of subjective daytime sleepiness (ESS ≥ 10) lasting 3 months or more, and not present prior to the TBI;
• Long sleep duration (mean TST ≥ 9hours/24hrs or increased sleep need of at least 1-2 h per 24 h compared to pre-TBI), documented by actigraphy, lasting 3 months or more;
• Objectively demonstrated EDS (MSLT mean of 5 naps: SL ≤ 8min);
• Age: 18 - 64;
• Ability to read and understand consent form, complete questionnaires and daily sleep diary, and provide informed consent. The Folstein MMSE will be used to assess cognitive function.

You may not qualify if:

• Current neurologic deficit (weakness, dysarthria or dysphagia, aphasia or dysphasia); Participants with a score of \<27 on Folstein MMSE will be excluded.
• History of neurologic or psychiatric disease prior to TBI;
• Epilepsy or history of seizure (whether related or unrelated to TBI);
• Body mass index (BMI) ≥ 32;
• Sleep apnea (Apnea Hypopnea Index, AHI \> 15/h); -Chronic sleep restriction (≥ 2hour sleep extension on weekends from self- report, diary, or at least 14 days of actigraphy);
• Sleep-wake disturbance other than long sleep duration or sleepiness (DSPD, ASPD, Shift-work Sleep Disorder);
• Diagnosis of narcolepsy or other sleep disorder prior to TBI;
• Unwillingness to follow physician instructions relating to the concomitant use of alcohol and sodium oxybate during the study;
• History of or current substance abuse;
• Current regular CNS-affecting medication use;
• History of depression, suicidal thoughts, and/or post-traumatic stress disorder (PTSD);
• Current depression assessed by a structured clinical interview and Beck Depression Inventory (BDI);
• Abnormal liver function (LFT more than twice the upper limit of normal or serum bilirubin more than 1.5 times the upper limit of normal);
• Hypertension, heart failure, history of myocardial infarction, or abnormal EKG demonstrating clinically significant arrhythmia;
• Kidney disease (Serum creatinine \>2.0mg/dl);

Sponsors & Collaborators

• Brigham and Women's Hospital: lead

Study Sites (1)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Disorders of Excessive Somnolence; Narcolepsy; Brain Injuries, Traumatic

Interventions

Sodium Oxybate

Condition Hierarchy (Ancestors)

Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Mental Disorders; Brain Injuries; Brain Diseases; Central Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries

Intervention Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Baldino Professor of Sleep Medicine, Division Chief

Study Record Dates

• First Submitted: June 27, 2018
• First Posted: August 13, 2018
• Study Start: September 1, 2020
• Primary Completion: September 1, 2020
• Study Completion: September 1, 2020
• Last Updated: March 4, 2021

Record last verified: 2021-03

Locations

US (1)