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

June 5, 2023 updated by: University Hospital, Clermont-Ferrand

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

90

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • France
      • Annecy, France, 74370
      • Clermont-Ferrand, France, 63000
      • Lille, France, 59000
      • Lyon, France, 69500
        • Recruiting
        • Hospices Civils de Lyon, Hôpital Pierre Wertheimer
        • Contact:
        • Principal Investigator:
          • Geneviève Demarquay
      • Marseille, France, 13005
        • Recruiting
        • AP-HM Marseille
        • Contact:
        • Principal Investigator:
          • Anne Donnet
      • Montpellier, France, 34295
      • Nantes, France, 44000
      • Paris, France, 75010
        • Recruiting
        • Hopital Lariboisiere
        • Contact:
        • Principal Investigator:
          • Caroline Roos
      • Rouen, France, 76100
      • Strasbourg, France, 67098

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 73 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Day 7
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
Day 8

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of 30% responders
Time Frame: day 7 to day 90
proportion of 30% responders at various time points according to the attack diary
day 7 to day 90
Proportion of 50% responders
Time Frame: day 7 to day 90
proportion of 50% responders at various time points according to the attack diary
day 7 to day 90
Proportion of 75% responders
Time Frame: day 7 to day 90
proportion of 75% responders at various time points according to the attack diary
day 7 to day 90
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
day 7
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
day 8
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)
day 0 to day 90
patient global impression of change (PGIC)
Time Frame: Day 8
PGIC will be completed and compared between the 2 groups
Day 8
patient global impression of change (PGIC)
Time Frame: Day 15
PGIC will be completed and compared between the 2 groups
Day 15
patient global impression of change (PGIC)
Time Frame: Day 29
PGIC will be completed and compared between the 2 groups
Day 29
patient global impression of change (PGIC)
Time Frame: Day 90
PGIC will be completed and compared between the 2 groups
Day 90
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)
day 0
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)
day 1
Proportion of patients necessitating rescue therapy
Time Frame: day 15
Proportion of patients necessitating rescue therapy (infusion of ketamine combined with magnesium)
day 15
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
day 7
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
day 8
Attacks treatment consumption
Time Frame: day 0 to day 90
Daily attacks treatment consumption (injectable sumatriptan and oxygene)
day 0 to day 90
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
day 0 to day 90
Anxiety evolution
Time Frame: Day 15
comparison of anxiety (evaluated via the HAD scale) between groups
Day 15
Anxiety evolution
Time Frame: Day 29
comparison of anxiety (evaluated via the HAD scale) between groups
Day 29
Anxiety evolution
Time Frame: Day 90
comparison of anxiety (evaluated via the HAD scale) between groups
Day 90
depression evolution
Time Frame: Day 15
comparison of depression (evaluated via the HAD scale) between groups
Day 15
depression evolution
Time Frame: Day 29
comparison of depression (evaluated via the HAD scale) between groups
Day 29
depression evolution
Time Frame: Day 90
comparison ofdepression (evaluated via the HAD scale) between groups
Day 90

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Clermont-Ferrand

Collaborators

Institut National de la Santé Et de la Recherche Médicale, France

Investigators

  • Principal Investigator: Xavier MOISSET, University Hospital, Clermont-Ferrand

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 15, 2021

Primary Completion (Estimated)

September 15, 2024

Study Completion (Estimated)

December 1, 2024

Study Registration Dates

First Submitted

March 18, 2021

First Submitted That Met QC Criteria

March 22, 2021

First Posted (Actual)

March 24, 2021

Study Record Updates

Last Update Posted (Actual)

June 7, 2023

Last Update Submitted That Met QC Criteria

June 5, 2023

Last Verified

June 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RBHP 2020 MOISSET
  • 2020-003604-14 (EudraCT Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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