Ketamine + Magnesium for Chronic Cluster Headache (KETALGIA)
- Conditions
- Refractory Chronic Cluster Headache
- Interventions
- Registration Number
- NCT04814381
- Lead Sponsor
- University Hospital, Clermont-Ferrand
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 90
- Age >= 18 years
- Chronic cluster headache diagnosis made according to ICHD-3 criteria
- A mean of at least 2 attacks/day during the 14 days before infusion
- Insufficient efficacy or intolerance or contra-indication to the use of the 3 main validated treatments (verapamil, lithium and sub-occipital steroids injections)
- Stable preventive treatment for at least 7 days before infusion
- Pregnant or lactating woman
- Contra-indication to ketamine use (uncontrolled high blood pressure, stoke history, severe cardiac failure)
- Ketamine use during the previous year
- Hypersensitivity to the product or their metabolites
- Severe renal insufficiency (creatinine clearance < 30ml/min)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Ketamine + Magnesium Ketamine + Magnesium sulfate (drug combination) 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%. Control 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
- Primary Outcome Measures
Name Time Method Change in weekly attacks between day 7 - day 13 period compared to the pre-treatment period pre-treatment period and day 7-day 13 post-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
- Secondary Outcome Measures
Name Time Method Proportion of 30% responders day 7 to day 90 proportion of 30% responders at various time points according to the attack diary
Proportion of 50% responders day 7 to day 90 proportion of 50% responders at various time points according to the attack diary
Proportion of 75% responders day 7 to day 90 proportion of 75% responders at various time points according to the attack diary
week by week attacks frequency day 0 to day 90 Area under the curve (AUC) for daily attacks evaluated each week between D0 and D90 (attacks diary)
patient global impression of change (PGIC) Day 90 PGIC will be completed and compared between the 2 groups
Infusion's safety day 1 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)
Proportion of patients necessitating rescue therapy Day 15 Proportion of patients necessitating rescue therapy (infusion of ketamine combined with magnesium)
Treatment response according to initial magnesemia day 8 magnesemia on the infusion day (D0) will be correlated with 50% response at D7-8 among patients receiving active treatment
Attacks treatment consumption day 0 to day 90 Daily attacks treatment consumption (injectable sumatriptan and oxygene)
Direct medical cost day 0 to day 90 Direct medical cost (treatments, consultations, hospitalisations) in each group and cost effectiveness ratio taking 50% responder rate as efficacy criteria
Anxiety evolution Day 90 comparison of anxiety (evaluated via the HAD scale) between groups
depression evolution Day 90 comparison ofdepression (evaluated via the HAD scale) between groups
Change in weekly attacks between day 14 - day 20 period compared to the pre-treatment period pre-treatment period and day 14 - day 20 post-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.
Change in weekly attacks between day 21 - day 27 period compared to the pre-treatment period pre-treatment period and day 21 - day 27 post-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.
Change in weekly attacks between day 28 - day 34 period compared to the pre-treatment period pre-treatment period and day 28 - day 34 post-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.
Adverse events assessment D0 to D90 assessment of blind quality Day 0 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.
Trial Locations
- Locations (14)
Polyclinique Jean Villar
🇫🇷Bruges, France
Clinique Beau Soleil
🇫🇷Montpellier, France
Hopital Pierre Paul Riquet
🇫🇷Toulouse, France
CHU Grenoble-Alpes
🇫🇷Voiron, France
CH Annecy Genevois
🇫🇷Annecy, France
CHU de Clermont-Ferrand
🇫🇷Clermont-Ferrand, France
CHRU De Lille
🇫🇷Lille, France
Hospices civils de Lyon, Hôpital Pierre Wertheimer
🇫🇷Lyon, France
AP-HM Marseille
🇫🇷Marseille, France
CHU de Montpellier
🇫🇷Montpellier, France
Scroll for more (4 remaining)Polyclinique Jean Villar🇫🇷Bruges, FranceVirginie Corand, Medical DoctorPrincipal Investigator