Clinical trial NCT04814381: Ketamine + Magnesium for Chronic Cluster Headache (KETALGIA)
Official title: Evaluation of the Efficacy of a Single Infusion of Ketamine Combined With Magnesium Sulfate to Treat Refractory Chronic Cluster Headache
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Refractory Chronic Cluster Headache
Keywords: Chronic cluster headache
Ketamine
Magnesium
Lead sponsor: University Hospital, Clermont-Ferrand
Sponsor class: OTHER
Collaborators: name: Institut National de la Santé Et de la Recherche Médicale, France
First posted: 2021-03-24
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: patients will be randomised with 1:1 ratio
Primary purpose: TREATMENT

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Proportion of 50% responders
timeFrame: Day 7
measure: Proportion of 50% responders
timeFrame: Day 8
Secondary outcomes:
measure: Proportion of 30% responders
timeFrame: day 7 to day 90
measure: Proportion of 50% responders
timeFrame: day 7 to day 90
measure: Proportion of 75% responders
timeFrame: day 7 to day 90
measure: attacks intensity
timeFrame: day 7
measure: attacks intensity
timeFrame: day 8
measure: week by week attacks frequency
timeFrame: day 0 to day 90
measure: patient global impression of change (PGIC)
timeFrame: Day 8
measure: patient global impression of change (PGIC)
timeFrame: Day 15
measure: patient global impression of change (PGIC)
timeFrame: Day 29
measure: patient global impression of change (PGIC)
timeFrame: Day 90
measure: Infusion's safety
timeFrame: day 0
measure: Infusion's safety
timeFrame: day 1
measure: Proportion of patients necessitating rescue therapy
timeFrame: day 15
measure: Treatment response according to initial magnesemia
timeFrame: day 7
measure: Treatment response according to initial magnesemia
timeFrame: day 8
measure: Attacks treatment consumption
timeFrame: day 0 to day 90
measure: Direct medical cost
timeFrame: day 0 to day 90
measure: Anxiety evolution
timeFrame: Day 15
measure: Anxiety evolution
timeFrame: Day 29
measure: Anxiety evolution
timeFrame: Day 90
measure: depression evolution
timeFrame: Day 15
measure: depression evolution
timeFrame: Day 29
measure: depression evolution
timeFrame: Day 90
Other outcomes:
Locations:
city: Annecy
country: France
facility: CH Annecy Genevois
city: Clermont-Ferrand
country: France
facility: CHU de Clermont-Ferrand
city: Lille
country: France
facility: CHRU De Lille
city: Lyon
country: France
facility: Hospices civils de Lyon, Hôpital Pierre Wertheimer
city: Marseille
country: France
facility: AP-HM Marseille
city: Montpellier
country: France
facility: CHU de Montpellier
city: Nantes
country: France
facility: CHU Nantes, Hopital Nord Laennec
city: Paris
country: France
facility: Hôpital Lariboisière
city: Rouen
country: France
facility: CHU Rouen
city: Strasbourg
country: France
facility: Hopital de Hautepierre
Study officials:
affiliation: University Hospital, Clermont-Ferrand
name: Xavier MOISSET
role: PRINCIPAL_INVESTIGATOR
References: