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 Proportion of 50% responders Day 8 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 the proportion of patients with at least 50% daily attacks decrease between the 7 days before infusion and days 7 and 8 after infusion
- 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 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)
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 50% responders day 7 to day 90 proportion of 50% responders at various time points according to the attack diary
attacks intensity day 8 evaluated on the electronic diary for each attack using a numeric rating scale (NRS), will be compared between the 7 days before infusion and the day 8 after infusion
patient global impression of change (PGIC) Day 90 PGIC will be completed and compared between the 2 groups
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
Trial Locations
- Locations (10)
CH Annecy Genevois
🇫🇷Annecy, France
Hospices civils de Lyon, Hôpital Pierre Wertheimer
🇫🇷Lyon, France
AP-HM Marseille
🇫🇷Marseille, France
CHU de Montpellier
🇫🇷Montpellier, France
CHU Rouen
🇫🇷Rouen, France
CHU de Clermont-Ferrand
🇫🇷Clermont-Ferrand, France
CHRU De Lille
🇫🇷Lille, France
Hôpital Lariboisière
🇫🇷Paris, France
Hopital de Hautepierre
🇫🇷Strasbourg, France
CHU Nantes, Hopital Nord Laennec
🇫🇷Nantes, France