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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
90
A single infusion will be performed over 2 hours with 90 days follow-up.
CH Annecy Genevois
Annecy, France
RECRUITINGPolyclinique Jean Villar
Bruges, France
RECRUITINGCHU de Clermont-Ferrand
Clermont-Ferrand, France
RECRUITINGCHRU De Lille
Lille, France
RECRUITINGHospices civils de Lyon, Hôpital Pierre Wertheimer
Lyon, France
RECRUITINGAP-HM Marseille
Marseille, France
RECRUITINGClinique Beau Soleil
Montpellier, France
RECRUITINGCHU de Montpellier
Montpellier, France
RECRUITINGCHU Nantes, Hopital Nord Laennec
Nantes, France
RECRUITINGHôpital Lariboisière
Paris, France
RECRUITING...and 4 more locations
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
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