NCT04814381

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.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
90

participants targeted

Target at P50-P75 for phase_4

Timeline
6mo left

Started Sep 2021

Longer than P75 for phase_4

Geographic Reach
1 country

14 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

Study Progress89%
Sep 2021Dec 2026

First Submitted

Initial submission to the registry

March 18, 2021

Completed
6 days until next milestone

First Posted

Study publicly available on registry

March 24, 2021

Completed
6 months until next milestone

Study Start

First participant enrolled

September 15, 2021

Completed
5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 15, 2026

Expected
3 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2026

Last Updated

July 16, 2025

Status Verified

October 1, 2024

Enrollment Period

5 years

First QC Date

March 18, 2021

Last Update Submit

July 15, 2025

Conditions

Keywords

Chronic cluster headacheKetamineMagnesium

Outcome Measures

Primary Outcomes (1)

  • Change in weekly attacks between day 7 - day 13 period compared to the pre-treatment period

    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 weekly attacks between day 7 and day 13 period and pre-treatment period

    pre-treatment period and day 7-day 13 post-treatment period

Secondary Outcomes (22)

  • Proportion of 30% responders

    day 7 to day 90

  • Proportion of 50% responders

    day 7 to day 90

  • Proportion of 75% responders

    day 7 to day 90

  • week by week attacks frequency

    day 0 to day 90

  • patient global impression of change (PGIC)

    Day 15

  • +17 more secondary outcomes

Study Arms (2)

Ketamine + Magnesium

EXPERIMENTAL

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)

Control

ACTIVE COMPARATOR

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)

Interventions

A single infusion will be performed over 2 hours with 90 days follow-up.

ControlKetamine + Magnesium

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (14)

CH Annecy Genevois

Annecy, 74370, France

RECRUITING

Polyclinique Jean Villar

Bruges, 33520, France

RECRUITING

CHU de Clermont-Ferrand

Clermont-Ferrand, 63000, France

RECRUITING

CHRU De Lille

Lille, 59000, France

RECRUITING

Hospices civils de Lyon, Hôpital Pierre Wertheimer

Lyon, 69500, France

RECRUITING

AP-HM Marseille

Marseille, 13005, France

RECRUITING

Clinique Beau Soleil

Montpellier, 34070, France

RECRUITING

CHU de Montpellier

Montpellier, 34295, France

RECRUITING

CHU Nantes, Hopital Nord Laennec

Nantes, 44000, France

RECRUITING

Hôpital Lariboisière

Paris, 75010, France

RECRUITING

CHU Rouen

Rouen, 76100, France

RECRUITING

Hopital de Hautepierre

Strasbourg, 67098, France

RECRUITING

Hopital Pierre Paul Riquet

Toulouse, 31059, France

RECRUITING

CHU Grenoble-Alpes

Voiron, 38500, France

NOT YET RECRUITING

MeSH Terms

Conditions

Cluster Headache

Interventions

KetamineMagnesium SulfateDrug Combinations

Condition Hierarchy (Ancestors)

Trigeminal Autonomic CephalalgiasHeadache Disorders, PrimaryHeadache DisordersBrain DiseasesCentral Nervous System DiseasesNervous System Diseases

Intervention Hierarchy (Ancestors)

CyclohexanesCycloparaffinsHydrocarbons, AlicyclicHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsMagnesium CompoundsInorganic ChemicalsSulfatesSulfuric AcidsSulfur AcidsSulfur CompoundsPharmaceutical Preparations

Study Officials

  • Xavier MOISSET

    University Hospital, Clermont-Ferrand

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Masking Details
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.
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: patients will be randomised with 1:1 ratio
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 18, 2021

First Posted

March 24, 2021

Study Start

September 15, 2021

Primary Completion (Estimated)

September 15, 2026

Study Completion (Estimated)

December 1, 2026

Last Updated

July 16, 2025

Record last verified: 2024-10

Data Sharing

IPD Sharing
Will not share

Locations