Ketamine + Magnesium for Chronic Cluster Headache (KETALGIA)

University Hospital, Clermont-Ferrand

Status and phase: Enrolling; Phase 4

Conditions: Refractory Chronic Cluster Headache

Treatments: Drug: Ketamine + Magnesium sulfate (drug combination)

Study type: Interventional

Funder types: Other

Identifiers

NCT04814381

RBHP 2020 MOISSET

2020-003604-14 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 90 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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90 participants in 2 patient groups

Ketamine + Magnesium

Experimental group

Description:

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%.

Treatment:

Drug: Ketamine + Magnesium sulfate (drug combination)

Control

Active Comparator group

Description:

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

Treatment:

Drug: Ketamine + Magnesium sulfate (drug combination)