This is an open label, investigator-sponsored, pilot study. Subjects agreeing to participate
in the study and meeting the eligibility criteria assessed at the screening visit will be
enrolled in the study. The length of time between screening and treatment will last between
0 days to a maximum of 12 weeks. Subjects who enter the screening phase during a cluster
headache episode and meet the study eligibility criteria can immediately enter the treatment
phase and may opt to treat their cluster headache episode in the clinic. Subjects who are
not in a cluster headache episode, who meet initial screening eligibility criteria, can
remain in the screening phase for up to 12 weeks until their next cluster episode begins.
Upon initiation of a cluster headache episode, subjects will enter the treatment period.
Subjects will be trained on the proper use of the hand-held dispenser containing carbon
dioxide (CO2 )calibrated to deliver 0.5 standard liters per minute (SLPM). This dispenser
will be provided for use in the clinic or home. Subjects will be instructed to use the nasal
CO2 dispenser, 10 seconds/nostril, as needed up to 6 times to treat one attack. Each dose
must be separated by 3-5 minutes. Subjects should treat only one attack in a 24-hour period.
Subjects may treat up to three cluster headache attacks during the treatment phase of this
study. One hour after the first dose, subjects can choose to treat with
investigator-approved rescue medication. Subjects will be asked to complete an online diary
after the completion of the dosing. Diary assessments will collect pain severity, nasal CO2
usage, acute medication usage, satisfaction of treatment, number of cluster attacks, and
unusual symptoms. Subjects will be contacted by phone within 3 days of the first use of the
nasal CO2 dispenser to assess adverse events (AEs) and medication usage. A total of 25
subjects will enter the treatment period and be instructed to treat up to 3 cluster
headaches with nasal CO2. Within 7 days of treating their last cluster headache episode,
subjects will return for an end of study visit.
- Male and female, 18 years of age and older.
- History of episodic cluster headache, as defined by International Classification of
Headache Disorders (ICHD), third edition, beta version guidelines (ICHD-3 beta,
- History of cluster headache attack-free remission periods lasting > 1 month within
the previous year.
- Stable on medications, including those for the treatment of cluster headache
prevention/prophylaxis, for at least 60 days prior to baseline (including, but not
limited to, verapamil, lithium, melatonin, any anticonvulsant, any systemic
corticosteroid or steroid injection, occipital nerve block, other cranial or
extracranial nerve block, or any neurostimulation treatment).
Note: Subjects are allowed to use their usual standard of care for the acute/abortive
treatment of acute cluster attacks 60 or more minutes after the initial dose, limited to
the following: triptans; high-flow oxygen.
- If female and of childbearing potential, have a negative urine pregnancy test at the
time of Screening.
a. To not be considered childbearing potential a subject must be surgically sterile,
have had a hysterectomy or tubal ligation, post-menopausal for at least 1 year, or
otherwise incapable of pregnancy.
- Capable of completing online headache diary with access to internet.
- Able to provide written Informed Consent.
- Recent nasal/midface trauma (< 3 months)
- Recent nasal/sinus surgery (< 3 months).
- Severe respiratory distress in the last 6 months.
- Neoplasm such as Angiofibroma, sinus tumor, granuloma.
- Nasal congestion present more than 10 days with fever (temperature ≥ 100.4 °F) and
nasal mucous is an abnormal color.
- Surgery to treat cluster headache.
- History of aneurysm, intracranial hemorrhage, brain tumors or significant head
- Structural intracranial or cervical vascular lesions that may potentially cause
- Other significant pain problems (including cancer pain, fibromyalgia, and trigeminal
neuralgia) that might confound the study assessments in the investigator opinion.
- Psychiatric disorder, which in the opinion of the Investigator, may interfere with
- Pregnant, actively trying to become pregnant, or breastfeeding, and/or is unwilling
to use an accepted form of birth control.
- Skin around and inside the nasal passage that is dry, cracked, oozing, or bleeding.
- Recurrent nose bleeds, which in the opinion of the Investigator, may interfere with
- Is participating in any other therapeutic clinical investigation or has participated
in a clinical trial and received treatment in the preceding 30 days.