A Phase 2 interventional study of Low Sodium Oxybate and Placebo in Chronic Cluster Headache, sponsored by Leiden University Medical Center. Not yet recruiting. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2026-08-25.
Sponsored by Leiden University Medical Center · Phase 2, Interventional, and Treatment
The goal of this clinical trial is to evaluate the efficacy of low sodium oxybate (LXB) (brand name Xywav) in the treatment of (nocturnal) cluster headache attacks in subjects with chronic cluster headache.
It is a 16 week, randomized, double-blind, placebo- controlled, bi-center trial.
LXB will be administered as a twice nightly regimen. All subjects will undergo an 6 week Treatment Titration and Optimization Phase.
The main trial endpoint is the change from baseline in average weekly frequency of nocturnal cluster headache attacks over 4-week fixed stable dose of treatment period.
The exact aetiology of cluster headache remains unknown and fundamental questions are still unanswered. However, the tendency of cluster headache attacks to occur during sleep suggests a pivotal role of the hypothalamus, a brain structure that regulates essential body functions such as sleep and the biological clock.
Low sodium oxybate (LXB) is a naturally occurring neurotransmitter and a psychoactive substance that deepens sleep by increasing slow wave sleep and reducing Rapid eye movement (REM) sleep. The chemical name of oxybate is gamma-hydroxybutyrate (GHB). The mechanism of action of LXB is still unknown. It is hypothesized that the therapeutic effects are mediated through GABA-B actions during sleep at noradrenergic and dopaminergic neurons, as well as at thalamocortical neurons.
We hypothesize that cluster headache attacks occur in relation to specific characteristics and time-points of the sleep microstructure and expect that a sleep-deepening treatment with LXB will reduce nocturnal attack-frequency and thereby improve sleep and quality of life.
The main objective of this study is to evaluate the efficacy and safety of LXB in the treatment of nocturnal cluster headache attacks in subjects with chronic cluster headache.
The main trial endpoint is the change from baseline in average weekly frequency of nocturnal cluster headache attacks over 4-week fixed stable dose of treatment period, comparing the LXB group with the placebo group. Nocturnal attacks are defined as attacks occurring between the time a participant goes to bed and the time they get out of bed, with a minimum window of 8 hours after bedtime.
Secondary endpoints include change from baseline in weekly frequency of cluster headache attacks in a 24-hr period (both nocturnal and day-time attacks) over 4-week fixed stable dose of treatment period. Additionally, the i) percentage of participants with a ≥50% reduction from baseline in the weekly number of nocturnal cluster headache attacks, ii) percentage of participants with a ≥50% reduction from baseline in the weekly number of cluster headache attacks in a 24-hr period (both nocturnal and day-time attacks) and iii) cluster headache attack pain intensity will be assessed over the 4-week fixed stable dose of treatment period, iv) Mean change in weekly number of times an abortive medication was taken v) number of patients with improvement in Patient Global Impressions Scale (PGIc) and Clinical Global Impressions Scale (CGIc) vi) improvement of sleep quality, sleep onset, sleep maintenance and sleep efficiency by diary. Optionally, two wearable skin sensors (Actiheart and CALERA Research) will be added for objective sleep and circadian rhythm measurements (including tri-axonal actigraphy, heart rate variability, core body temperature).
123 studies on the registry are indexed under Cluster Headache; 26 are open to participants now.
This study's planned enrollment of 52 is above the median of 42 across 90 interventional studies indexed under Cluster Headache.
Browse Cluster Headache studies →Leiden University Medical Center is the lead sponsor of 334 studies on the registry; 110 are open to participants now.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Age ≥18 and ≤75 at the time of consent.
Diagnosed with chronic cluster headache according to the International Classification of Headache Disorders (ICHD-III) criteria.
Free of other cluster headache prophylactic medication OR on stable dose for at least 4 weeks.
Not having received a GON (Greater Occipital Nerve) injection or oral prednisone in the previous 3 months.
At least 4 nocturnal cluster headache attacks per week (defined as occurring after sleep onset during the night between 22:00 and 08:00), not exclusively appearing during a single night, but spread across multiple nights.
Exclusion criteria
Suspected of having another trigeminal autonomic cephalalgia (TAC).
Other headaches if the patient cannot reliably distinguish them from cluster headache attacks.
Weight at inclusion of \<50kg or >120kg.
Significant active or unstable psychiatric disease in the opinion of the investigator.
Significant pulmonary or neuromuscular diseases in the opinion of the investigator.
A history of or current indication of substance abuse or substance use disorder.
Unwillingness to refrain from consuming ≤ 1 alcohol unit per day and not later than 8 pm.
Stimulator devices which could influence sleep or cluster headache symptoms, such as an occipital nerve stimulator (ONS), when settings have not been stable for at least three months prior to screening.
Participation in a clinical trial of an investigation drug or device in the past 30 days.
Women who are pregnant/breastfeeding. Woman of childbearing age need to agree to sufficient during the trial.
for using LXB:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Low Sodium Oxybate (LXB) In this study we will use XYWAV, also known as JZP-258, oral solution 0.5 g/mL (Jazz Pharmaceuticals) for deepening sleep. JZP-258 is an oral solution containing LXB and is a central nervous system depressant. LXB will be administered as a twice nightly regimen. All subjects will undergo an 6 week Treatment Titration and Optimization Phase.
Drug: Low Sodium Oxybate
Placebo will be administered as a twice nightly regimen. All subjects will undergo an 6 week Treatment Titration and Optimization Phase.
Drug: Placebo
Low sodium oxybate (LXB) will be administered as a twice nightly regimen. All subjects will undergo an 6 week Treatment Titration and Optimization Phase. Titration should proceed in an increment of 1.5g per night each 7 days until a 50% reduction in nocturnal headache frequency is achieved or a maximum dose (9g per night) is reached. If a subject is unable to titrate to a higher dose, they may stay at the highest tolerated dose for the duration of the study. Subjects may stop titration or have dose reduction at any time for safety and tolerability reasons.
Also known as: XYWAV, JZP-258
Placebo with equal appearance
Change in average weekly frequency of nocturnal cluster headache attacks (verum vs placebo)
During 4-week fixed stable dose treatment phase compared to baseline. Nocturnal attacks are defined as attacks occurring between the time a participant goes to bed and the time they get out of bed, with a minimum window of 8 hours after bedtime. (verum vs placebo)
Time frame: During 4-week fixed stable dose treatment phase
Change in percentage of participants with a ≥30% reduction in the weekly number of nocturnal Cluster Headache Attacks
At week during 4-week fixed stable dose treatment phase compared to baseline.
Time frame: During 4-week fixed stable dose
Change in percentage of participants with a ≥50% reduction in the weekly number of nocturnal Cluster Headache Attacks
During 4-week fixed stable dose treatment phase compared to baseline.
Time frame: During 4-week fixed stable dose
Change in weekly frequency of cluster headache attacks in a 24-hr period during
During a 4-week fixed stable dose treatment phase compared to baseline.
Time frame: During a 4-week fixed stable dose
Change in percentage of participants with a ≥30% reduction in the weekly number of cluster headache attacks in a 24-hr period (daytime and nocturnal attacks)
During 4-week fixed stable dose treatment phase compared to baseline.
Time frame: During 4-week fixed stable dose
Change in percentage of participants with a ≥50% reduction in the weekly number of cluster headache attacks in a 24-hr period (daytime and nocturnal attacks)
During 4-week fixed stable dose treatment phase compared to baseline.
Time frame: During 4-week fixed stable dose
Change in pain scale (NRS 0-10)
During 4-week fixed stable dose treatment phase compared to baseline.
Time frame: During 4-week fixed stable dose
No study locations are listed for this record.
This study is not yet recruiting, as verified in Aug 2026. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: JZP258
Leiden University Medical Center →