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Ketamine + Magnesium for Chronic Cluster Headache (KETALGIA) (KETALGIA)

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ClinicalTrials.gov Identifier: NCT04814381
Recruitment Status : Recruiting
First Posted : March 24, 2021
Last Update Posted : September 22, 2021
Sponsor:
Information provided by (Responsible Party):
University Hospital, Clermont-Ferrand

Study Description
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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.


Condition or disease Intervention/treatment Phase
Refractory Chronic Cluster Headache Drug: Ketamine + Magnesium sulfate (drug combination) Phase 4

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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: patients will be randomised with 1:1 ratio
Masking: Double (Participant, Investigator)
Masking Description: infusion will be prepared by a nurse that is not blinded to the treatment and will not take part to patient evaluation. Active and control treatments are of transparent colour and will not be recognisable.
Primary Purpose: Treatment
Official Title: Evaluation of the Efficacy of a Single Infusion of Ketamine Combined With Magnesium Sulfate to Treat Refractory Chronic Cluster Headache
Actual Study Start Date : September 15, 2021
Estimated Primary Completion Date : September 2024
Estimated Study Completion Date : December 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Headache

Arms and Interventions
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Arm Intervention/treatment
Experimental: Ketamine + Magnesium
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%.
 Drug: Ketamine + Magnesium sulfate (drug combination)
A single infusion will be performed over 2 hours with 90 days follow-up.
Active Comparator: Control
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
 Drug: Ketamine + Magnesium sulfate (drug combination)
A single infusion will be performed over 2 hours with 90 days follow-up.


Outcome Measures
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Primary Outcome Measures :
  1. Proportion of 50% responders [ Time Frame: Day 7 ]
    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

  2. Proportion of 50% responders [ Time Frame: 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 :
  1. Proportion of 30% responders [ Time Frame: day 7 to day 90 ]
    proportion of 30% responders at various time points according to the attack diary

  2. Proportion of 50% responders [ Time Frame: day 7 to day 90 ]
    proportion of 50% responders at various time points according to the attack diary

  3. Proportion of 75% responders [ Time Frame: day 7 to day 90 ]
    proportion of 75% responders at various time points according to the attack diary

  4. attacks intensity [ Time Frame: day 7 ]
    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

  5. attacks intensity [ Time Frame: 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

  6. week by week attacks frequency [ Time Frame: day 0 to day 90 ]
    Area under the curve (AUC) for daily attacks evaluated each week between D0 and D90 (attacks diary)

  7. patient global impression of change (PGIC) [ Time Frame: Day 8 ]
    PGIC will be completed and compared between the 2 groups

  8. patient global impression of change (PGIC) [ Time Frame: Day 15 ]
    PGIC will be completed and compared between the 2 groups

  9. patient global impression of change (PGIC) [ Time Frame: Day 29 ]
    PGIC will be completed and compared between the 2 groups

  10. patient global impression of change (PGIC) [ Time Frame: Day 90 ]
    PGIC will be completed and compared between the 2 groups

  11. Infusion's safety [ Time Frame: day 0 ]
    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)

  12. Infusion's safety [ Time Frame: 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)

  13. Proportion of patients necessitating rescue therapy [ Time Frame: day 15 ]
    Proportion of patients necessitating rescue therapy (infusion of ketamine combined with magnesium)

  14. Treatment response according to initial magnesemia [ Time Frame: day 7 ]
    magnesemia on the infusion day (D0) will be correlated with 50% response at D7-8 among patients receiving active treatment

  15. Treatment response according to initial magnesemia [ Time Frame: day 8 ]
    magnesemia on the infusion day (D0) will be correlated with 50% response at D7-8 among patients receiving active treatment

  16. Attacks treatment consumption [ Time Frame: day 0 to day 90 ]
    Daily attacks treatment consumption (injectable sumatriptan and oxygene)

  17. Direct medical cost [ Time Frame: 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

  18. Anxiety evolution [ Time Frame: Day 15 ]
    comparison of anxiety (evaluated via the HAD scale) between groups

  19. Anxiety evolution [ Time Frame: Day 29 ]
    comparison of anxiety (evaluated via the HAD scale) between groups

  20. Anxiety evolution [ Time Frame: Day 90 ]
    comparison of anxiety (evaluated via the HAD scale) between groups

  21. depression evolution [ Time Frame: Day 15 ]
    comparison of depression (evaluated via the HAD scale) between groups

  22. depression evolution [ Time Frame: Day 29 ]
    comparison of depression (evaluated via the HAD scale) between groups

  23. depression evolution [ Time Frame: Day 90 ]
    comparison ofdepression (evaluated via the HAD scale) between groups


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04814381


Contacts
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Contact: Lise LACLAUTRE +33473754963 promo_interne_drci@chu-clermontferrand.fr

Locations
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France
CH Annecy Genevois Not yet recruiting
Annecy, France, 74370
Contact: Pierric Giraud       pgiraud@ch-annecygenevois.fr   
Principal Investigator: Pierric Giraud         
CHU de Clermont-Ferrand Recruiting
Clermont-Ferrand, France, 63000
Contact: Lise Laclautre    +33473754963    promo_interne_drci@chu-clermontferrand.fr   
Principal Investigator: Xavier Moisset         
CHRU De Lille Not yet recruiting
Lille, France, 59000
Contact: Christian Lucas       Christian.LUCAS@chru-lille.fr   
Principal Investigator: Christian Lucas         
Hospices civils de Lyon, Hôpital Pierre Wertheimer Not yet recruiting
Lyon, France, 69500
Contact: Geneviève Demarquay       genevieve.demarquay@chu-lyon.fr   
Principal Investigator: Geneviève Demarquay         
AP-HM Marseille Not yet recruiting
Marseille, France, 13005
Contact: Anne Donnet       Anne.DONNET@ap-hm.fr   
Principal Investigator: Anne Donnet         
CHU de Montpellier Not yet recruiting
Montpellier, France, 34295
Contact: Anne Ducros       a-ducros@chu-montpellier.fr   
Principal Investigator: Anne Ducros         
CHU Nice Not yet recruiting
Nice, France, 06000
Contact: Michel Lantéri-Minet       lanteri-minet.m@chu-nice.fr   
Principal Investigator: Michel Lantéri-Minet         
Hôpital Lariboisière Not yet recruiting
Paris, France, 75010
Contact: Caroline Roos       caroline.roos@aphp.fr   
Principal Investigator: Caroline Roos         
Hopital de Hautepierre Recruiting
Strasbourg, France, 67098
Contact: Eric Salvat       eric.salvat@chru-strasbourg.fr   
Principal Investigator: Eric Salvat         
Sponsors and Collaborators
University Hospital, Clermont-Ferrand
Investigators
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Principal Investigator: Xavier MOISSET University Hospital, Clermont-Ferrand
More Information
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Responsible Party: University Hospital, Clermont-Ferrand
ClinicalTrials.gov Identifier: NCT04814381    
Other Study ID Numbers: RBHP 2020 MOISSET
2020-003604-14 ( EudraCT Number )
First Posted: March 24, 2021    Key Record Dates
Last Update Posted: September 22, 2021
Last Verified: September 2021

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University Hospital, Clermont-Ferrand:
Chronic cluster headache
Ketamine
Magnesium
Additional relevant MeSH terms:
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Cluster Headache
Headache
Pain
Neurologic Manifestations
Trigeminal Autonomic Cephalalgias
Headache Disorders, Primary
Headache Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Magnesium Sulfate
Ketamine
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
 Physiological Effects of Drugs
Anesthetics, Dissociative
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
Central Nervous System Depressants
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Anti-Arrhythmia Agents
Anticonvulsants
Calcium Channel Blockers
Membrane Transport Modulators
Calcium-Regulating Hormones and Agents