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

NCT ID: NCT03626727

Last Updated: 2021-03-04

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: EARLY_PHASE1
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-09-30
• Study Completion Date: 2020-09-01

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.

Conditions

Hypersomnia; Narcolepsy; Traumatic Brain Injury

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Sodium Oxybate Oral Solution (Xyrem®)

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.

Group Type: EXPERIMENTAL

Sodium Oxybate Oral Solution [Xyrem]

Intervention Type: DRUG

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

Interventions

Sodium Oxybate Oral Solution [Xyrem]

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

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 64 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Brigham and Women's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Charles Andrew Czeisler, MD, PhD

Baldino Professor of Sleep Medicine, Division Chief

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Brigham and Women's Hospital

Boston, Massachusetts, United States

Countries

United States

Other Identifiers

2017-P-002884

Identifier Type: -

Identifier Source: org_study_id