Clinical trial NCT03626727: Evaluation of the Efficacy of Sodium Oxybate (Xyrem®) in Treatment of Post-traumatic Narcolepsy and Post-traumatic Hypersomnia
Official title: Open-label Clinical Trial to Evaluate the Efficacy of Sodium Oxybate (Xyrem®) in the Treatment of Two Under-recognized Clinical Conditions: Post-traumatic Narcolepsy and Post-traumatic Hypersomnia
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: EARLY_PHASE1
Conditions: Hypersomnia
Narcolepsy
Traumatic Brain Injury
Keywords: Excessive Daytime Sleepiness
Prolonged sleep
Traumatic Brain Injury
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
First posted: 2018-08-13
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Detailed description: Post-traumatic narcolepsy and post-traumatic hypersomnia are under-recognized clinical conditions in post-TBI patients.

Considering the high prevalence of hypersomnia, treatment difficulty, and sparse clinical studies for treatment of sleep problems in TBI patients, additional clinical trials need to be performed to provide more therapeutic options for patients and physicians. Sodium oxybate (Xyrem®) could be potentially one such option given its high efficacy in idiopathic narcolepsy patients.

From the results of animal research, as well as from cerebrospinal fluid (CSF) and autopsy findings from TBI patients, hypothalamic injury and hypocretin pathology seem to play a role in the pathogenesis of post-traumatic narcolepsy and hypersomnia. Despite lack of clear understanding of the exact mechanism of action of sodium oxybate in patients with idiopathic narcolepsy, the shared pathophysiology of the hypocretin system in post-traumatic hypersomnia and narcolepsy would suggest the possible efficacy of sodium oxybate (Xyrem®) on excessive daytime sleepiness (EDS) and prolonged sleep in patients with TBI.

In this Pilot Clinical Trial, we will test whether sodium oxybate (Xyrem®, approved for the treatment of improve wakefulness in adult patients with excessive sleepiness associated with narcolepsy) is effective in improving the sleep-wake symptoms, global functioning and quality of life of post-TBI patients with hypersomnia and narcolepsy.

Eligibility criteria: Inclusion Criteria:

* History of first-ever primary TBI 12 or more months ago;
* Mild to severe TBI (GCS 3-15);
* Either a) or b):

  1. Presence of subjective daytime sleepiness (ESS ≥ 10) lasting 3 months or more, and not present prior to the TBI;
  2. 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.

Exclusion Criteria:

* 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);
* Lung disease (COPD, ILD, asthma);
* On a low salt diet for medical reasons;
* An occupation that requires variable shift work or routine night shifts (work hours between 11pm and 6am);
* Pregnant, intention to become pregnant;
* Breast-feeding or plans to breastfeed;
* Succinic semialdehyde dehydrogenase deficiency.

Primary outcomes:
measure: Change in Subjective Daytime Sleepiness
timeFrame: 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.
measure: Change in Sleep Duration
timeFrame: 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.
measure: Change in Clinical Condition
timeFrame: 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.
measure: Change in Subjective Daytime Sleepiness (ESS)
timeFrame: 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:
measure: Change in Nocturnal Sleep Quality (Frequency of nocturnal awakenings)
timeFrame: 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.
measure: Change in Nocturnal Sleep Quality (Duration of nocturnal awakenings)
timeFrame: 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.
measure: Change in Nocturnal Sleep Quality (Subjective amount of sleep)
timeFrame: 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.
measure: Change in Nocturnal Sleep Quality (Frequency of sleep walking)
timeFrame: 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.
measure: Change in Nocturnal Sleep Quality (Frequency of hypnagogic hallucinations)
timeFrame: 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.
measure: Change in Nocturnal Sleep Quality (Change in Pittsburgh Sleep Quality index) scores)
timeFrame: 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.
measure: Change in Nocturnal Sleep Quality (actigraphy)
timeFrame: 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.
measure: Change in Global Functioning
timeFrame: 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.
Other outcomes:
Locations:
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
Study officials:
References: