Headache disorders — including chronic daily headache, tension-type headache, and cluster headache — affect hundreds of millions of people. While migraine has its own dedicated research track, trials under the headache umbrella cover the full range of types that don't respond well to standard over-the-counter treatments. Treatment varies from preventive medications and nerve blocks to behavioral therapies.
What's actually going on in research
Trials are testing CGRP-blocking drugs that were developed for migraine and are now being studied in other chronic headache types, nerve stimulation devices, Botox injections, and behavioral treatments including biofeedback. Researchers are also studying the overlap between sleep, mood disorders, and chronic head pain.
CGRP pathway drugs
Drugs blocking a protein called CGRP have changed migraine treatment. Trials are now testing whether these drugs also help people with chronic daily headache, cluster headache, and post-traumatic headache.
Nerve stimulation
Devices that stimulate the occipital nerve or vagus nerve are being tested as an alternative to daily medication, particularly for people who don't tolerate drugs well or whose headaches haven't responded.
Post-injury and medication-overuse headache
Trials are specifically targeting headaches caused by overusing pain medication and headaches that follow concussion or brain injury — two groups that often fall through gaps in existing treatments.
What to know before you search
Eligibility typically depends on headache type and frequency, prior treatments tried, presence of migraine versus other headache diagnoses, medication use patterns, and whether you are in a headache cycle.
What types of trials are currently open
- Preventive medication trials — Testing drugs taken daily to reduce how often headaches occur, including repurposed drugs from other conditions and new ones targeting headache-specific pathways.
- Device trials — Testing external nerve stimulators worn on the forehead, neck, or ear that deliver electrical pulses to disrupt pain signals without medication.
- Injection and nerve block trials — Testing Botox, nerve blocks, or steroid injections to reduce headache frequency in patients with chronic daily headache.
- Behavioral therapy trials — Testing mindfulness, cognitive behavioral therapy, and biofeedback as standalone or add-on treatments for people with frequent headaches.
- Cluster headache trials — Testing treatments specifically for cluster headache — a severe type that comes in cycles — where few good options exist.
Recently added Headache trials
Epidural Hydroxyethyl Starch for Post-Dural Puncture Headache in Parturients
The incidence of accidental dural puncture (ADP) among parturients receiving neuraxial labor analgesia has been reported to range from 1% to 1.5%. Post-dural puncture headache (PDPH) is a headache caused by low cerebrospinal fluid pressure resulting from substantial cerebrospinal fluid leakage after dural and arachnoid puncture. Epidural filling with hydroxyethyl starch (HES) via an epidural catheter has been used to prevent PDPH in patients with ADP. This multicenter prospective cohort study aimed to evaluate the effect of epidural HES filling in preventing PDPH in parturients who experienced ADP during epidural labor analgesia or neuraxial anesthesia for cesarean delivery.
Oral Gabapentin Versus Intravenous Neostigmine/Atropine Versus Combination of Both for Prevention of PDPH
Post-dural puncture headache (PDPH) is a major complication of neuraxial anaesthesia. Pain is intense, frontal, throbbing, and radiates to the occiput; it is more severe when standing and less severe when lying down. A lot of studies reported several techniques for management of post-dural puncture headache including conservative, pharmacological or interventional techniques. Conservative techniques such as hydration and bed rest. These therapies aim to decrease CSF loss through the dural hole and restore CSF with additional fluid intake. Pharmacological treatment such as caffeine , methylxanthine (as theophylline), gabapentinoids, Sumatriptan, cosyntropin, dexamethasone, intravenous (IV) injection of ondansetron and IV opioid were used. Also, there are several interventional treatments like), epidural blood patch greater occipital nerve block, and sphenopalatine ganglion block has been used. Neostigmine has a biphasic effect on sympathetic ganglia, ie, depolarization followed by hyperpolarization. results in vasoconstriction reflects sympathetic regulation of the blood supply to cerebral vessels . An increase in central acetylcholine can maintain cerebral vasoconstriction Atropine crosses the blood brain barrier and is a parasympatholytic , it increases CSF secretion by antagonizing the effect of acetylcholine on the choroid plexus Gabapentin is an anti-epileptic, similar in structure to the endogenous neurotransmitter gamma-amino-butyric acid, but their exact mechanism for treating PDPH is unclear. A possible mechanism for gabapentin-mediated analgesia is the modulation of glutamate receptors (N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) /kainite). Also it inhibits nociceptive responses to intrathecal NMDA and AMPA in vivo.
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