Refractory Chronic Cluster Headache Clinical Trial
— KETALGIAOfficial title:
Evaluation of the Efficacy of a Single Infusion of Ketamine Combined With Magnesium Sulfate to Treat Refractory Chronic Cluster Headache
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.
| Status | Recruiting |
| Enrollment | 90 |
| Est. completion date | December 2024 |
| Est. primary completion date | September 15, 2024 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years to 75 Years |
| Eligibility | Inclusion Criteria: - 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 Exclusion Criteria: - 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) |
| Country | Name | City | State |
|---|---|---|---|
| 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 | CHU Nantes, Hopital Nord Laennec | Nantes | |
| France | Hôpital Lariboisière | Paris | |
| France | CHU Rouen | Rouen | |
| France | Hopital de Hautepierre | Strasbourg |
| Lead Sponsor | Collaborator |
|---|---|
| University Hospital, Clermont-Ferrand | Institut National de la Santé Et de la Recherche Médicale, France |
France,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Proportion of 50% responders | 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 | Day 7 | |
| Primary | Proportion of 50% responders | 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 | Day 8 | |
| Secondary | Proportion of 30% responders | proportion of 30% responders at various time points according to the attack diary | day 7 to day 90 | |
| Secondary | Proportion of 50% responders | proportion of 50% responders at various time points according to the attack diary | day 7 to day 90 | |
| Secondary | Proportion of 75% responders | proportion of 75% responders at various time points according to the attack diary | day 7 to day 90 | |
| Secondary | attacks intensity | 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 7 after infusion | day 7 | |
| Secondary | attacks intensity | 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 | day 8 | |
| Secondary | week by week attacks frequency | Area under the curve (AUC) for daily attacks evaluated each week between D0 and D90 (attacks diary) | day 0 to day 90 | |
| Secondary | patient global impression of change (PGIC) | PGIC will be completed and compared between the 2 groups | Day 8 | |
| Secondary | patient global impression of change (PGIC) | PGIC will be completed and compared between the 2 groups | Day 15 | |
| Secondary | patient global impression of change (PGIC) | PGIC will be completed and compared between the 2 groups | Day 29 | |
| Secondary | patient global impression of change (PGIC) | PGIC will be completed and compared between the 2 groups | Day 90 | |
| Secondary | 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) | day 0 | |
| Secondary | 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) | day 1 | |
| Secondary | Proportion of patients necessitating rescue therapy | Proportion of patients necessitating rescue therapy (infusion of ketamine combined with magnesium) | day 15 | |
| Secondary | 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 | day 7 | |
| Secondary | 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 | day 8 | |
| Secondary | Attacks treatment consumption | Daily attacks treatment consumption (injectable sumatriptan and oxygene) | day 0 to day 90 | |
| Secondary | Direct medical cost | Direct medical cost (treatments, consultations, hospitalisations) in each group and cost effectiveness ratio taking 50% responder rate as efficacy criteria | day 0 to day 90 | |
| Secondary | Anxiety evolution | comparison of anxiety (evaluated via the HAD scale) between groups | Day 15 | |
| Secondary | Anxiety evolution | comparison of anxiety (evaluated via the HAD scale) between groups | Day 29 | |
| Secondary | Anxiety evolution | comparison of anxiety (evaluated via the HAD scale) between groups | Day 90 | |
| Secondary | depression evolution | comparison of depression (evaluated via the HAD scale) between groups | Day 15 | |
| Secondary | depression evolution | comparison of depression (evaluated via the HAD scale) between groups | Day 29 | |
| Secondary | depression evolution | comparison ofdepression (evaluated via the HAD scale) between groups | Day 90 |
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Recruiting |
NCT02081482 -
Cerebral Metabolism in Patients With Refractory Chronic Cluster Headache Treated by Occipital Nerve Stimulation
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N/A |