A Phase 4 interventional study of Ketamine + Magnesium sulfate (drug combination) in Refractory Chronic Cluster Headache, sponsored by University Hospital, Clermont-Ferrand. Completed at 14 sites in France. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2026-05-08.
Sponsored by University Hospital, Clermont-Ferrand · Phase 4, Interventional, and Treatment
Chronic cluster headache (CCH) is a rare primary headache disorder, defined by episodic attacks that occur for more than one year with no remission period or with remission periods lasting \< 3 months (ICHD-3 criteria). In certain cases, CCH patients become drug-resistant and continue to suffer almost daily attacks.
Ketamine appears to be effective in a variety of chronic pain conditions, such as refractory headache, and can show an enhanced analgesic effect when combined with magnesium. A single infusion of ketamine-magnesium combination has been described to reduce attacks in 17 patients with rCCH. The main outcome was a comparison of the number of daily attacks two weeks prior to the infusion and one week after (days 7-8). The number of daily attacks decreased from 4.3±2.4 before treatment to 1.3±1.0 after treatment (p\<0.001). 13/17 had at least 50% response. Thus, the goal of this placebo-controlled study is to try to confirm these findings.
Chronic cluster headache (CCH) is a rare primary headache disorder, defined by episodic attacks that occur for more than one year with no remission period or with remission periods lasting \< 3 months (ICHD-3 criteria). In certain cases, CCH patients become drug-resistant and continue to suffer almost daily attacks.
Ketamine appears to be effective in a variety of chronic pain conditions, such as refractory headache, and can show an enhanced analgesic effect when combined with magnesium. A single infusion of ketamine-magnesium combination has been described to reduce attacks in 17 patients with rCCH. The main outcome was a comparison of the number of daily attacks two weeks prior to the infusion and one week after (days 7-8). The number of daily attacks decreased from 4.3±2.4 before treatment to 1.3±1.0 after treatment (p\<0.001). 13/17 had at least 50% response. Thus, the goal of this placebo-controlled study is to try to confirm these findings.
123 studies on the registry are indexed under Cluster Headache; 26 are open to participants now.
This study's enrollment of 93 is above the median of 42 across 90 interventional studies indexed under Cluster Headache.
Browse Cluster Headache studies →University Hospital, Clermont-Ferrand is the lead sponsor of 859 studies on the registry; 179 are open to participants now.
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Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Creatinine clearance (CrCl)
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
patients in the experimental group will receive 0.5mg/kg of ketamine over 2 hours, diluted in 50cc of NaCl 0.9% and 3g of magnesium sulfate over 30 minutes diluted in 250cc of NaCl 0.9%.
Drug: Ketamine + Magnesium sulfate (drug combination)
patients in the control group will receive 25mg of hydroxyzine over 2 hours, diluted in 50cc of NaCl 0.9% and 250cc of NaCl 0.9% over 30 minutes
Drug: Ketamine + Magnesium sulfate (drug combination)
Drug page: Drug Combinations
A single infusion will be performed over 2 hours with 90 days follow-up.
Change in weekly attacks between day 7 - day 13 period compared to the pre-treatment period
Evaluate the efficacy of a single infusion of ketamine combined with magnesium sulfate compared to a control group receiving hydroxyzine (active placebo) in terms of weekly attacks between day 7 and day 13 period and pre-treatment period
Time frame: pre-treatment period and day 7-day 13 post-treatment period
Proportion of 30% responders
proportion of 30% responders at various time points according to the attack diary
Time frame: day 7 to day 90
Proportion of 50% responders
proportion of 50% responders at various time points according to the attack diary
Time frame: day 7 to day 90
Proportion of 75% responders
proportion of 75% responders at various time points according to the attack diary
Time frame: day 7 to day 90
week by week attacks frequency
Area under the curve (AUC) for daily attacks evaluated each week between D0 and D90 (attacks diary)
Time frame: day 0 to day 90
patient global impression of change (PGIC)
PGIC will be completed and compared between the 2 groups
Time frame: Day 15
patient global impression of change (PGIC)
PGIC will be completed and compared between the 2 groups
Time frame: Day 90
Infusion's safety
proportion of patients in each group reporting any side effect during or in the 24 hours after infusion (together with the type and intensity of these side effects)
Time frame: day 0
Infusion's safety
proportion of patients in each group reporting any side effect during or in the 24 hours after infusion (together with the type and intensity of these side effects)
Time frame: day 1
Proportion of patients necessitating rescue therapy
Proportion of patients necessitating rescue therapy (infusion of ketamine combined with magnesium)
Time frame: Day 15
Treatment response according to initial magnesemia
magnesemia on the infusion day (D0) will be correlated with 50% response at D7-8 among patients receiving active treatment
Time frame: day 7
Treatment response according to initial magnesemia
magnesemia on the infusion day (D0) will be correlated with 50% response at D7-8 among patients receiving active treatment
Time frame: day 8
Attacks treatment consumption
Daily attacks treatment consumption (injectable sumatriptan and oxygene)
Time frame: day 0 to day 90
Direct medical cost
Direct medical cost (treatments, consultations, hospitalisations) in each group and cost effectiveness ratio taking 50% responder rate as efficacy criteria
Time frame: day 0 to day 90
Anxiety evolution
comparison of anxiety (evaluated via the HAD scale) between groups
Time frame: Day 15
Anxiety evolution
comparison of anxiety (evaluated via the HAD scale) between groups
Time frame: Day 90
depression evolution
comparison of depression (evaluated via the HAD scale) between groups
Time frame: Day 15
depression evolution
comparison ofdepression (evaluated via the HAD scale) between groups
Time frame: Day 90
Change in weekly attacks between day 14 - day 20 period compared to the pre-treatment period
Evaluate the efficacy of a single infusion of ketamine combined with magnesium sulfate compared to a control group receiving hydroxyzine (active placebo) in terms of weekly attacks between day 14 and day 20 post-reatment period and pre-treatment period. The number of weekly attacks will be evaluated using a attacks diary that patients will complete every day.
Time frame: pre-treatment period and day 14 - day 20 post-treatment period
Change in weekly attacks between day 21 - day 27 period compared to the pre-treatment period
Evaluate the efficacy of a single infusion of ketamine combined with magnesium sulfate compared to a control group receiving hydroxyzine (active placebo) in terms of weekly attacks between day 21 and day 27 post-reatment period and pre-treatment period. The number of weekly attacks will be evaluated using a attacks diary that patients will complete every day.
Time frame: pre-treatment period and day 21 - day 27 post-treatment period
Change in weekly attacks between day 28 - day 34 period compared to the pre-treatment period
Evaluate the efficacy of a single infusion of ketamine combined with magnesium sulfate compared to a control group receiving hydroxyzine (active placebo) in terms of weekly attacks between day 28 and day 34 post-treatment period and pre-treatment period. The number of weekly attacks will be evaluated using a attacks diary that patients will complete every day.
Time frame: pre-treatment period and day 28 - day 34 post-treatment period
Adverse events assessment
Time frame: D0 to D90
assessment of blind quality
A blinding questionnaire will be systematically used to assess the quality of the blind. It will be completed by each patient 30 minutes after the end of the 1st infusion at day 0 (Visit 1). The patient will be asked what treatment he thinks he has received.
Time frame: Day 0
This study is completed, as verified in May 2026. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Drug Combinations
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