Efficacy, Safety and Tolerability of Low Sodium Oxybate for Nocturnal Cluster Headache Attacks

NCT06950281 | Not Yet Recruiting Phase 2 FDA Drug

• 1 other identifier: 136324
• Study Type: interventional
• Target: 52
• Locations: 0 countries
• Sites: N/A

Brief Summary

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 an 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.

Conditions

Chronic Cluster Headache

Outcome Measures

Primary Outcomes (1)

• 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 occurring after sleep onset during the night between 22:00 and 07:00. (verum vs placebo)

  During 4-week fixed stable dose treatment phase

Secondary Outcomes (6)

• Change in percentage of participants with a ≥30% reduction in the weekly number of nocturnal Cluster Headache Attacks

  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

• Change in weekly frequency of cluster headache attacks in a 24-hr period during

  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

• 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

Study Arms (2)

Verum

EXPERIMENTAL

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

PLACEBO COMPARATOR

Placebo will be administered as a twice nightly regimen. All subjects will undergo an 6 week Treatment Titration and Optimization Phase.

Drug: Placebo

Interventions

Low Sodium Oxybate DRUG

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

Verum

Placebo DRUG

Placebo with equal appearance

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Suspected of having another trigeminal autonomic cephalalgia (TAC).
• Other headaches if the patient cannot reliably distinguish them from cluster headache attacks.
• 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 contraception during the trial.
• Contraindications for using LXB:
• Sleep apnoea syndrome or increased apnoea index (AI \> 15/h).
• High risk of sleep apnoea syndrome, indicated by the STOP-Bang questionnaire (score ≥ 5).
• Currently suffering from severe depression and using medication or receiving cognitive therapy. Final choice is at the discretion of the principal investigator.
• Porphyria.
• Succinic semialdehyde dehydrogenase (SSADH-)deficiency.

Sponsors & Collaborators

• Leiden University Medical Center: lead

MeSH Terms

Conditions

Cluster Headache

Condition Hierarchy (Ancestors)

Trigeminal Autonomic Cephalalgias; Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Central Study Contacts

Martien van Liefland, MD

CONTACT

+31 71 5262587; SUNCET@lumc.nl

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Model Details: A 16 week, randomized, double-blind, placebo- controlled study.

Study Record Dates

• First Submitted: April 15, 2025
• First Posted: April 30, 2025
• Study Start: January 1, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): May 1, 2028
• Last Updated: November 24, 2025

Record last verified: 2025-04