HypersomniaEarly Phase 1NCT03626727

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

A Early Phase 1 study testing Sodium Oxybate Oral Solution [Xyrem] in people with Hypersomnia and Narcolepsy, run by Brigham and Women's Hospital at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 to 64 years
Conditions the study is for: Hypersomnia, Narcolepsy, Traumatic Brain Injury
What is being tested?: Sodium Oxybate Oral Solution [Xyrem]
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 0 participants
Where: 1 siteUnited States
Study dates: Sep 2020to 1 Sep 2020
Phase: Early Phase 1
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 64 years
All sexes
No healthy volunteers
Adult

Who may be able to join

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.

Who cannot join

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);

Show all 21Show fewer

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.

Trial locations and contacts

1 site in 1 country.

United States1 site

Brigham and Women's Hospital
Boston, Massachusetts, 02115

Other trials in United States

About this study

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

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.

Read the 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
Being tested: Sodium Oxybate Oral Solution [Xyrem]
Keywords: Excessive Daytime Sleepiness, Prolonged sleep, Traumatic Brain Injury
Medical subject headings: Disorders of Excessive Somnolence, Narcolepsy, Brain Injuries, Traumatic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

Study groups in NCT03626727
Study group	Role	What they receive
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. Receives: Drug: Sodium Oxybate Oral Solution [Xyrem]

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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)
Average change in nocturnal sleep quality assessed by a daily sleep questionnaire on frequency of nocturnal awakenings.
Measured: 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)
Average change in nocturnal sleep quality assessed by a daily sleep questionnaire on duration of nocturnal awakenings.
Measured: 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)
Average change in nocturnal sleep quality assessed by a daily sleep questionnaire on subjective amount of sleep each night.
Measured: 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)
Average change in nocturnal sleep quality assessed by a daily sleep questionnaire on frequency of sleep walking.
Measured: 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)
Average change in nocturnal sleep quality assessed by a daily sleep questionnaire on frequency of hypnagogic hallucinations.
Measured: 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 (Change in Pittsburgh Sleep Quality index) scores)
Average change in nocturnal sleep quality assessed by changes in Pittsburgh Sleep Quality Index (PSQI) scores. The PSQI assesses sleep quality. It is broken down into seven components, with scales from 0 - 3 with 0 being better quality of sleep and 3 being a more poor quality of sleep. The Global PSQI score is taken from the sum of the seven component scores.
Measured: 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 (actigraphy)
Average change in nocturnal sleep quality measured by actigraphy.
Measured: 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 Global Functioning
Change in global functioning evaluated by the Sheehan Disability Scale (SDS). The SDS assesses functional impairment in three subscales: in work/school, social, and family life. Each is subscale is 1-10 with 1 being no disability/impairment and 10 be extreme disability/impairment. These three subscales are added together to give the global functional impairment score which ranges from 0 being unimpaired to 30 being highly impaired.
Measured: 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.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Sep 20201 Sep 2020

First posted13 Aug 2018
Study startSep 2020 (estimated)
Primary completion1 Sep 2020
Study completion1 Sep 2020

Why it stopped: Target study population was extremely difficult to recruit and planned study budget was exceeded

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for HypersomniaStudies of the same condition, open and under way.
More trials run by Brigham and Women's HospitalThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Early Phase 1
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 0 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03626727
Sponsor's protocol ID: 2017-P-002884
Status last verified: Mar 2021
First submitted: 27 Jun 2018
Last updated: 4 Mar 2021
Results posted: No
FDA-regulated drug: Yes
FDA-regulated device: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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RecruitingPhase 2/3
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RecruitingPhase 3
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All Hypersomnia trials

Study at a glance

From the registry record, last updated by the sponsor on 4 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT03626727
Acronym / sponsor ID: 2017-P-002884
Conditions: Hypersomnia, Narcolepsy, Traumatic Brain Injury
Keywords: Excessive Daytime Sleepiness, Prolonged sleep, Traumatic Brain Injury
Phase: Early Phase 1
Study type: Interventional
Recruitment status: WithdrawnReason stopped: Target study population was extremely difficult to recruit and planned study budget was exceeded
Enrolment: 0 participants (actual)
Lead sponsor: Brigham and Women's HospitalUniversity, hospital or other
Study start: Sep 2020 (estimated)
Primary completion: 1 Sep 2020 (actual)
Study completion: 1 Sep 2020 (actual)
First posted: 13 Aug 2018 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Sodium Oxybate Oral Solution (Xyrem®)	Experimental	Drug: 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.

Who may qualify

Ages: 18 to 64 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult

Key inclusion criteria (8 listed)

History of first-ever primary TBI 12 or more months ago;
Mild to severe TBI (GCS 3-15);
Either a) or b):
Objectively demonstrated EDS (MSLT mean of 5 naps: SL ≤ 8min);
Age: 18 - 64;

Key exclusion criteria (21 listed)

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);

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
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	Drug	Sodium Oxybate Oral Solution (Xyrem®)

Primary outcome

Change in Subjective Daytime Sleepiness
Time frame: 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 assessed through a daily questionnaire about frequency and duration of daytime naps, frequency of sleep attacks.
Change in Sleep Duration
Time frame: 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 assessed by actigraphy-estimated total sleep time (TST).
Change in Clinical Condition
Time frame: 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 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.
Change in Subjective Daytime Sleepiness (ESS)
Time frame: 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 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.

8 secondary outcomes

Change in Nocturnal Sleep Quality (Frequency of nocturnal awakenings)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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 (Change in Pittsburgh Sleep Quality index) scores)
Time frame: 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 (actigraphy)
Time frame: 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 Global Functioning
Time frame: 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.

Results and safety

The study was withdrawn before enrolling participants, so there are no results.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2021.

Related trials for Hypersomnia

RecruitingPhase 2/3
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RecruitingPhase 2/3
A Study to Investigate the Effects of Cleminorexton Compared With Placebo in the Treatment of Participants With Central Disorders of Hypersomnolence
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RecruitingPhase 3
A Study Evaluating the Efficacy and Safety of Xywav Expanded Dosing vs Placebo in Participants With Narcolepsy or IH
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing Sodium Oxybate Oral Solution [Xyrem] in people with Hypersomnia and Narcolepsy, run by Brigham and Women's Hospital at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 4 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Subjective Daytime Sleepiness (time frame: 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.). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03626727.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Mar 2021.