Cluster headache syndrome

Summary

Cluster headache syndrome (MONDO:0043537) is a disease and 105 clinical trials. Top therapeutic interventions include fremanezumab, galcanezumab, and oxybate. A subtype of brain disorder — broader associated-gene and molecular evidence is on the parent page (see Disease family below).

At a glance

• Clinical trials: 105

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	cluster headache syndrome
Mondo ID	MONDO:0043537
MeSH	D003027
Orphanet	1002
ICD-11	760621151
NCIT	C117077
SNOMED CT	193031009
UMLS	C0009088
MedGen	3503
Is cancer (heuristic)	no

Also known as: atypical cluster headache · atypical cluster headaches · beuralgias, ciliary · Cephalgia, histamine · Cephalgias, histamine · chronic cluster headache · chronic cluster headaches · ciliary neuralgia · ciliary neuralgias · cluster headache · cluster headache syndrome · cluster headache syndromes · cluster headache, atypical · cluster headache, chronic · cluster headache, episodic · cluster headaches · cluster headaches, atypical · cluster headaches, chronic · cluster headaches, episodic · cluster migraine (+34 more)

Disease family

This is a subtype of brain disorder. Genetic, therapeutic, and trial evidence is largely curated at the broader-term level — see the parent page for the associated-gene cohort and molecular evidence.

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › brain disorder › cluster headache syndrome

Related subtypes (70): leukoencephalopathy, megalencephalic, encephalopathy, acute, infection-induced, diabetic encephalopathy, complex cortical dysplasia with other brain malformations, hydrocephalus, brain compression, cerebral sarcoidosis, hepatic encephalopathy, visual pathway disorder, central nervous system origin vertigo, cerebellar disorder, cerebritis, olfactory nerve disorder, thalamic disorder, pituitary gland disorder, disorder of optic chiasm, basal ganglia disorder, epilepsy, mental disorder, central nervous system cyst, migraine disorder, multiple sclerosis, prion disease, carbon monoxide-induced delayed encephalopathy, cerebral malaria, akinetic mutism, bulbar polio, Reye syndrome, brain edema, encephalomalacia, intracranial hypertension, intracranial hypotension, Wernicke encephalopathy, encephalopathy, recurrent, of childhood, XK aprosencephaly, progressive bulbar palsy, cerebrovascular disorder, glycine encephalopathy, autosomal recessive frontotemporal pachygyria, occipital pachygyria and polymicrogyria, insomnia, narcolepsy-cataplexy syndrome, megalencephaly, meningoencephalocele, cerebral cortical dysplasia, encephaloclastic disorder, bilirubin encephalopathy, autoimmune encephalopathy with parasomnia and obstructive sleep apnea, narcolepsy without cataplexy, hypothalamic hamartomas with gelastic seizures, encephalitis, cerebral lipidosis with dementia, brain neoplasm, colpocephaly, corpus callosum agenesis of blepharophimosis robin type, corpus callosum dysgenesis X-linked recessive, corpus callosum dysgenesis cleft spasm, corpus callosum dysgenesis hypopituitarism, cerebral degeneration, acute bilirubin encephalopathy, chronic bilirubin encephalopathy, atelencephaly, aprosencephaly, brain injury, traumatic encephalopathy, cerebral cortex disorder, midbrain disorder, encephalopathy due to mitochondrial and peroxisomal fission defect, brain malformations with or without urinary tract defects, encephalopathy, acute transient

Subtypes (1): cluster headache, familial

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

No associated-gene cohort resolved for this disease. Atlas builds the molecular and therapeutic sections — associated genes, protein families, druggability, pathways, interactions, and drug associations — by aggregating over a disease’s associated genes (resolved via GWAS / GenCC / ClinVar / CIViC), and none resolved here. This is expected for antibody-mediated, autoimmune, or otherwise non-gene-defined conditions; the curated evidence for this disease is its clinical features, GWAS susceptibility, and clinical trials (above).

Function

No pathway enrichment — requires an associated-gene cohort.

Therapeutics

Drugs indicated or in trials for this disease

No drug has an approved disease-direct ChEMBL indication for this disease.

1 drug in clinical trials for this disease (phase 2–3, investigational): efficacy not established — a trial record, not an indication.

Drug	Highest phase
Ergocalciferol	Phase 3

Clinical trials & evidence

Clinical trials

Clinical trials: 105.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	63
PHASE3	15
PHASE2	10
PHASE4	6
PHASE1/PHASE2	4
PHASE1	4
PHASE2/PHASE3	3

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04406259	PHASE4	ACTIVE_NOT_RECRUITING	Atrioventricular Block and Cluster Headache (SEVA)
NCT00203190	PHASE4	TERMINATED	A Double-Blind, Placebo-Controlled Study Examining the Use of Topiramate in the Treatment of Cluster Headache
NCT00399243	PHASE4	UNKNOWN	Sumatriptan 4 mg Statdose in the Acute Treatment of Cluster Headache
NCT03377257	PHASE4	UNKNOWN	Efficacy and Safety of Zolmitriptan by Sublingual Administration
NCT04014634	PHASE4	COMPLETED	GON-injection for a Sooner and Better Treatment of Cluster Headache
NCT04814381	PHASE4	COMPLETED	Ketamine + Magnesium for Chronic Cluster Headache (KETALGIA)
NCT03944876	PHASE3	RECRUITING	Botulinum Toxin Type A Blockade of the Sphenopalatine Ganglion in Treatment-refractory Chronic Cluster Headache
NCT05324748	PHASE3	RECRUITING	Repeated GON Injections in CCH
NCT00033839	PHASE3	COMPLETED	A Phase III Study of Civamide Nasal Solution (Zucapsaicin) for the Treatment of Episodic Cluster Headache
NCT00069082	PHASE3	COMPLETED	Intranasal Civamide for Episodic Cluster Headache
NCT00804895	PHASE2/PHASE3	COMPLETED	Cluster Headache Cortivazol Injection (CHCI)
NCT01151631	PHASE3	COMPLETED	Occipital Nerve Stimulation in Medically Intractable Chronic Cluster Headache
NCT01341548	PHASE3	UNKNOWN	Civamide Nasal Solution for Cluster Headache
NCT02397473	PHASE3	COMPLETED	A Study Of Galcanezumab In Participants With Episodic Cluster Headache
NCT02438826	PHASE3	COMPLETED	A Study of Galcanezumab in Participants With Chronic Cluster Headache
NCT02462395	PHASE2/PHASE3	COMPLETED	Anodal Transcranial Direct Stimulation (tDCS) for the Treatment of Chronic Cluster Headache
NCT02637648	PHASE3	UNKNOWN	Sodium Oxybate in Patients With Episodic and Chronic Cluster Headache
NCT02797951	PHASE3	COMPLETED	A Study of LY2951742 (Galcanezumab) in Participants With Cluster Headache
NCT02945046	PHASE3	TERMINATED	A Study to Evaluate the Efficacy and Safety of TEV-48125 (Fremanezumab) for the Prevention of Episodic Cluster Headache (ECH)
NCT02964338	PHASE3	TERMINATED	A Study Comparing the Efficacy and Safety of Fremanezumab (TEV-48125) for the Prevention of Chronic Cluster Headache (CCH)
NCT03107052	PHASE3	TERMINATED	A Study to Explore the Long-Term Safety and Efficacy of Fremanezumab (TEV-48125) for the Prevention of Cluster Headache
NCT04066023	PHASE2/PHASE3	COMPLETED	Double-Blind Comparison of the Efficacy and Safety of C213 to Placebo for the Acute Treatment of Cluster Headaches
NCT04688775	PHASE3	COMPLETED	Eptinezumab in Participants With Episodic Cluster Headache
NCT05064397	PHASE3	COMPLETED	A 1-year Trial to Inform About Long-term Exposure to Eptinezumab in Participants With Chronic Cluster Headache (cCH)
NCT03781128	PHASE2	RECRUITING	Lysergic Acid Diethylamide (LSD) as Treatment for Cluster Headache
NCT04930887	PHASE2	RECRUITING	Clinical Trial of Endoscopically Guided Injection of Exparel (Bupivacaine) for the Treatment of Craniofacial Pain
NCT05477459	PHASE2	RECRUITING	LSD to Improve Cluster Headache Impact Trial
NCT06950281	PHASE2	NOT_YET_RECRUITING	Efficacy, Safety and Tolerability of Low Sodium Oxybate for Nocturnal Cluster Headache Attacks
NCT00184587	PHASE2	COMPLETED	Prophylactic Treatment of Episodic Cluster Headache
NCT01701245	PHASE2	COMPLETED	Prevention and Acute Treatment of Chronic Cluster Headache Compared to Standard of Care
NCT02019017	PHASE1/PHASE2	COMPLETED	Botox Injection in Treatment of Cluster Headache
NCT02209155	PHASE2	TERMINATED	R-Verapamil for the Prophylaxis of Episodic Cluster Headache
NCT02381795	PHASE2	TERMINATED	Pilot Study Evaluating the Use of Nasal Carbon Dioxide for the Treatment of Cluster Headache
NCT03066635	PHASE1/PHASE2	COMPLETED	Botulinum Toxin Type A Block of the Otic Ganglion in Chronic Cluster Headache: Safety Issues
NCT04179266	PHASE1/PHASE2	COMPLETED	Effect of Ketamine Intranasal Spray in Treatment of Chronic Cluster Headache
NCT04280055	PHASE1/PHASE2	TERMINATED	Prophylactic Effects of Psilocybin on Chronic Cluster Headache
NCT04970355	PHASE2	COMPLETED	Efficacy of Erenumab in Chronic Cluster Headache
NCT05264714	PHASE2	COMPLETED	Cluster Headache Treatment With Rimegepant
NCT03511846	PHASE1	ENROLLING_BY_INVITATION	Pain Biomarker Study
NCT01298921	PHASE1	TERMINATED	A Pilot Study of Demand Valve Oxygen Inhalation Therapy for Cluster Headache

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
FREMANEZUMAB	4	3
GALCANEZUMAB	4	3
OXYBATE	4	3
EPTINEZUMAB	4	2
VERAPAMIL	4	2
CANDESARTAN CILEXETIL	4	1
CAPSAICIN	4	1
CORTIVAZOL	4	1
DIVALPROEX SODIUM	4	1
ERENUMAB	4	1
METHYLPREDNISOLONE	4	1
RIMEGEPANT	4	1
TOPIRAMATE	4	1
ZUCAPSAICIN	3	3
MAGNESIUM	3	1
PSILOCYBIN	3	1
DEXVERAPAMIL	2	2
LEVCROMAKALIM	2	1
LYSERGIDE	2	1
MEBUFOTENIN	2	1
CHEMBL5170372	0	1
AIR, MEDICAL	-1	1