Ongoing Clinical Trials for Cluster Headache
There are currently 5 clinical trials underway exploring new treatments for cluster headache, a severe neurological condition characterized by intense, recurring headaches. These studies are investigating various approaches including nerve blocks, brain imaging techniques, and medications such as botulinum toxin, LSD, corticosteroids, and ketamine. Trials are being conducted across several European countries including France, Germany, Netherlands, and Norway.
Clinical trial locations
- France
- Germany
- Netherlands
- Norway
Study on Botulinum Toxin Type A and Sodium Chloride for Patients with Treatment-Resistant Chronic Cluster Headache
This trial is investigating whether botulinum toxin type A, commonly known as Botox, can help people with chronic cluster headaches that have not responded to standard medications. The treatment targets a specific group of nerve cells in the head called the sphenopalatine ganglion, which is linked to headache pain.
Who can participate: Adults aged 18 to 85 years who have chronic cluster headaches according to international diagnostic criteria. Participants must experience at least 4 headache attacks per week, with at least 80% of attacks occurring on the same side of the head. The condition must be treatment-resistant, meaning that medications like verapamil, lithium, or steroid injections have not worked, caused severe side effects, or cannot be used. Participants must maintain their current preventive medication regimen without changes throughout the study. Women of childbearing age must use effective birth control for 4 weeks after the injection.
Who cannot participate: People who do not meet the diagnostic criteria for chronic cluster headaches, those outside the specified age range, and individuals who belong to vulnerable populations requiring special protection.
Main focus: The study aims to determine whether botulinum toxin type A injections directed at the sphenopalatine ganglion can reduce the frequency and intensity of headache attacks. The primary observation period occurs between weeks 5 and 8 after treatment, with additional monitoring continuing through weeks 9 to 12. Researchers will compare results between those receiving the active treatment and those receiving a placebo.
Investigational treatment: Botulinum toxin type A is administered as a single injection using an image-guided surgical device to ensure precise targeting of the sphenopalatine ganglion.
Study on Cluster Headache Using Befiradol (18F) for Patients with Episodic Symptoms
This trial uses advanced brain imaging technology to better understand what happens in the brain during different phases of cluster headaches. Unlike the other trials, this study focuses on episodic cluster headaches rather than the chronic form.
Who can participate: Male patients aged 20 to 45 years, weighing between 50 and 110 kg, who experience pain episodes between 11:00 a.m. and 9:00 p.m. Participants must have no history of psychiatric or neurological conditions other than cluster headaches, and no history of head trauma with loss of consciousness lasting more than 30 minutes. They must be affiliated with social security or a similar system and must provide written informed consent.
Who cannot participate: Patients with any other nervous system diseases, female patients, and individuals considered part of vulnerable populations.
Main focus: The study uses PET-MRI imaging combined with a radiotracer called Befiradol (18F) to examine brain activity and blood flow during both active and inactive periods of the disease. Researchers aim to identify differences in brain function and connectivity before, during, and after headache attacks, which could lead to better understanding of the condition and improved treatments.
Investigational treatment: Befiradol (18F), also known as [18F]F13640, is a radiotracer administered through injection to help visualize brain activity during imaging sessions.
Study on the Effects of Lysergide for Patients with Chronic Cluster Headache
This trial is testing whether very small doses of lysergic acid diethylamide, commonly known as LSD, can reduce the frequency of headache attacks in people with chronic cluster headaches.
Who can participate: Adults aged 16 to 75 years with a diagnosis of chronic cluster headache according to international criteria. During the screening period, participants must have experienced an average of at least 8 headache attacks per week over the past 4 weeks, with weekly attack numbers staying within 40% of the average. At randomization, these criteria must still be met, and there can be no more than 2 consecutive days without attacks. Participants must be on a stable preventive treatment regimen and agree not to change doses or start new treatments during the study. Women of childbearing age must have a negative pregnancy test before starting and must use reliable birth control during the study and for 1 week after the last dose.
Who cannot participate: People without chronic cluster headaches, those outside the age range, and vulnerable populations.
Main focus: The study evaluates whether taking 25 micrograms of LSD every 3 days over a 3-week period can safely reduce headache frequency. Participants are randomly assigned to receive either the active medication or a placebo, and headache patterns are monitored throughout the treatment period to assess effectiveness and safety.
Investigational treatment: Lysergide D-tartrate (LSD) is administered as an oral solution in microdoses of 25 micrograms.
Study on Repeated Corticosteroid Injections with Methylprednisolone Acetate and Sodium Chloride for Patients with Chronic Cluster Headache
This trial investigates whether repeated corticosteroid injections around the Greater Occipital Nerve can provide long-term relief from chronic cluster headaches.
Who can participate: Adults aged 18 years and older with chronic cluster headaches according to international diagnostic criteria. The headache pain must always occur on the same side of the head. Participants must have at least 4 headache attacks per week during a one-month baseline observation period. They must be on a stable preventive treatment plan for more than 4 weeks before starting the study and agree not to increase doses or start new preventive treatments during the trial.
Who cannot participate: People not experiencing cluster headaches, those under 18 years old, and vulnerable populations.
Main focus: The study examines whether repeated injections of methylprednisolone acetate around the Greater Occipital Nerve can safely and effectively reduce headache frequency over the long term. Researchers will monitor the frequency, duration, and severity of attacks, as well as quality of life and any side effects. The study also tracks how long patients remain in the trial and the intervals between injections.
Investigational treatment: Methylprednisolone acetate (Depo-Medrone) and sodium chloride are administered as subcutaneous injections around the Greater Occipital Nerve, with treatment repeated as needed over the study period.
Study on Ketamine and Magnesium Sulfate for Treating Chronic Cluster Headache in Patients Unresponsive to Standard Treatments
This trial explores whether a combination of ketamine and magnesium sulfate, given as a single intravenous infusion, can help people with chronic cluster headaches who have not responded to standard treatments.
Who can participate: Adults aged 18 years and older with chronic cluster headaches according to international criteria. Participants must experience at least 2 headache attacks per day on average during the 14 days before receiving treatment. They must have tried and found three major treatments (verapamil, lithium, and corticosteroids) to be ineffective, poorly tolerated, or unsuitable. Participants must provide informed consent after understanding the study details.
Who cannot participate: People without refractory chronic cluster headaches, those outside the age range of 18 to 65 years, and vulnerable populations.
Main focus: The study evaluates whether a single intravenous infusion of ketamine combined with magnesium sulfate can reduce the frequency and intensity of headache attacks. Researchers will monitor headache patterns over several weeks following the infusion, comparing results to a control group receiving hydroxyzine as an active placebo. The study also assesses changes in anxiety and depression levels and any side effects experienced.
Investigational treatments: Ketamine and magnesium sulfate are administered together as a single intravenous infusion. Ketamine is an anesthetic that affects brain chemicals to help decrease pain, while magnesium sulfate may enhance pain relief by relaxing blood vessels and reducing inflammation.
Summary
The 5 ongoing clinical trials for cluster headache reflect diverse approaches to treating this challenging condition. The trials are concentrated in Western Europe, with the Netherlands hosting 2 studies, and France, Germany, and Norway each hosting 1 or more studies.
Four of the five trials focus specifically on chronic cluster headache, which is the more difficult-to-treat form of the condition. Only one trial examines episodic cluster headaches and uses advanced brain imaging rather than testing a treatment intervention. This suggests that research efforts are particularly focused on finding solutions for patients whose condition has not responded to standard therapies.
The investigational treatments span a wide range of mechanisms, including nerve blocks with botulinum toxin and corticosteroids, psychedelic microdosing with LSD, and intravenous infusions combining ketamine with magnesium sulfate. This variety indicates that researchers are exploring multiple pathways to pain relief, from blocking specific nerve signals to modulating brain chemistry and reducing inflammation.
Most trials have specific requirements regarding headache frequency, typically requiring at least 4 to 8 attacks per week, and many require that standard treatments have already been tried without success. This focus on treatment-resistant cases highlights the urgent need for new therapeutic options for patients who continue to suffer despite existing medications.
