Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
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

Tracking Information
First Submitted Date  ICMJE March 18, 2021
First Posted Date  ICMJE March 24, 2021
Last Update Posted Date September 22, 2021
Actual Study Start Date  ICMJE September 15, 2021
Estimated Primary Completion Date September 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 22, 2021)
  • 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
  • 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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 22, 2021)
  • Proportion of 30% responders [ Time Frame: day 7 to day 90 ]
    proportion of 30% responders at various time points according to the attack diary
  • Proportion of 50% responders [ Time Frame: day 7 to day 90 ]
    proportion of 50% responders at various time points according to the attack diary
  • Proportion of 75% responders [ Time Frame: day 7 to day 90 ]
    proportion of 75% responders at various time points according to the attack diary
  • 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
  • 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
  • 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)
  • patient global impression of change (PGIC) [ Time Frame: Day 8 ]
    PGIC will be completed and compared between the 2 groups
  • patient global impression of change (PGIC) [ Time Frame: Day 15 ]
    PGIC will be completed and compared between the 2 groups
  • patient global impression of change (PGIC) [ Time Frame: Day 29 ]
    PGIC will be completed and compared between the 2 groups
  • patient global impression of change (PGIC) [ Time Frame: Day 90 ]
    PGIC will be completed and compared between the 2 groups
  • 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)
  • 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)
  • Proportion of patients necessitating rescue therapy [ Time Frame: day 15 ]
    Proportion of patients necessitating rescue therapy (infusion of ketamine combined with magnesium)
  • 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
  • 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
  • Attacks treatment consumption [ Time Frame: day 0 to day 90 ]
    Daily attacks treatment consumption (injectable sumatriptan and oxygene)
  • 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
  • Anxiety evolution [ Time Frame: Day 15 ]
    comparison of anxiety (evaluated via the HAD scale) between groups
  • Anxiety evolution [ Time Frame: Day 29 ]
    comparison of anxiety (evaluated via the HAD scale) between groups
  • Anxiety evolution [ Time Frame: Day 90 ]
    comparison of anxiety (evaluated via the HAD scale) between groups
  • depression evolution [ Time Frame: Day 15 ]
    comparison of depression (evaluated via the HAD scale) between groups
  • depression evolution [ Time Frame: Day 29 ]
    comparison of depression (evaluated via the HAD scale) between groups
  • depression evolution [ Time Frame: Day 90 ]
    comparison ofdepression (evaluated via the HAD scale) between groups
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Ketamine + Magnesium for Chronic Cluster Headache (KETALGIA)
Official Title  ICMJE Evaluation of the Efficacy of a Single Infusion of Ketamine Combined With Magnesium Sulfate to Treat Refractory Chronic Cluster Headache
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE 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
Condition  ICMJE Refractory Chronic Cluster Headache
Intervention  ICMJE Drug: Ketamine + Magnesium sulfate (drug combination)
A single infusion will be performed over 2 hours with 90 days follow-up.
Study Arms  ICMJE
  • 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%.
    Intervention: Drug: Ketamine + Magnesium sulfate (drug combination)
  • 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
    Intervention: Drug: Ketamine + Magnesium sulfate (drug combination)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 22, 2021)
90
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2024
Estimated Primary Completion Date September 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Lise LACLAUTRE +33473754963 promo_interne_drci@chu-clermontferrand.fr
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04814381
Other Study ID Numbers  ICMJE RBHP 2020 MOISSET
2020-003604-14 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party University Hospital, Clermont-Ferrand
Original Responsible Party Same as current
Current Study Sponsor  ICMJE University Hospital, Clermont-Ferrand
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Xavier MOISSET University Hospital, Clermont-Ferrand
PRS Account University Hospital, Clermont-Ferrand
Verification Date September 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP