GON-injection for a Sooner and Better Treatment of Cluster Headache (CHIANTI)

GON-injection for a Sooner and Better Treatment of Cluster Headache: a Double-blind Randomized Controlled Trial

Cluster headache is a very severe primary headache disorder. In episodic cluster headache, attacks occur in 'bouts' (clusters) lasting weeks to months. Management of cluster headache entails a combination of attack and prophylactic treatment. Current first choice prophylactic treatment (verapamil) has considerable side effects which can be serious and include possibly fatal cardiac arrhythmias; and it can take weeks to titrate to an effective dose. Evidence has emerged that local steroid injection of the greater occipital nerve (GON) may be effective in cluster headache, but this method has not been investigated as a first line prophylactic treatment in a large, well-documented group of episodic cluster headache patients who are still free of prophylactic medication and just entered a new cluster headache episode. As such, GON-injection has not yet found its way into current treatment protocols. The investigators plan to perform this multicentre double-blind randomized controlled trial to investigate whether GON-injection is efficacious as a first-line prophylactic treatment, aiming to remove the need for high doses of daily medication - such as verapamil - with associated side effects.

Study Overview

• Status: Completed
• Conditions: Cluster Headache, Episodic; Greater Occipital Nerve Injection
• Intervention / Treatment: Other: Placebo; Drug: Methylprednisolone

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Roemer Brandt, MD; Phone Number: 0031620063703; Email: r.b.brandt@lumc.nl
• Study Contact Backup: Name: Rolf Fronczek, MD, PhD; Email: r.fronczek@lumc.nl

Study Locations

• Netherlands
  • Blaricum, Netherlands
    • Tergooi Ziekenhuis
  • Heerlen, Netherlands
    • Zuyderland Medisch Centrum
  • Nijmegen, Netherlands
    • Canisius-Wilhelmina Hospital
  • Noord Holland
    • Amsterdam, Noord Holland, Netherlands
      • Boerhaave Clinics
  • Zuid Holland
    • Leiden, Zuid Holland, Netherlands
      • LUMC
    • Leiderdorp, Zuid Holland, Netherlands
      • Alrijne Ziekenhuis

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients have to be diagnosed with episodic cluster headache according to the international classification of headache disorders - third edition, ICHD-3
• Patients have to be aged 18-65 years
• Patients need to be newly diagnosed and treatment naïve, or already diagnosed and currently free from prophylactic treatment
• Patients need to have a mean of 1 or more attacks per day in the 3 days preceding inclusion.
• Patients should be in their cluster period for shorter than 4 weeks before inclusion.

Exclusion Criteria:

• A contraindication for treatment with steroids or verapamil
• The use of anticoagulants or known bleeding disorder.
• Use of any prophylactic medication for cluster headache
• Patients with a history of other primary headache who are currently using prophylactic medication for this headache
• Pregnancy

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Verum	Drug: Methylprednisolone; Single GON injection with methylprednisolone
Placebo Comparator: Placebo; Injection of NaCl	Other: Placebo; Single GON-injection with NaCl

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Verapamil mean total dose	Difference in mean total dose of verapamil used during the study period	12 week period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Days to remission	Median number of days to remission (7 consecutive days without attack)	12 weeks
Daily attacks	Mean number of attacks per day during the study period	12 weeks
Peak dose verapamil	Peak dose verapamil	12 weeks
Preamature termination	Premature termination of study due to need for escape medication	12 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Use of attack medication	The total use of attack medication (stratified for oxygen and sumatriptan)	12 weeks
Daily attack severity and duration	Mean number, severity (1-10) and duration of attack per day.	For the total study period and each of the three consecutive 4-week time periods
Attack-freedom	Percentage of patients that are attack-free at days 7, 14 and 28	days 7, 14 and 28
Non-cluster headache	Occurrence of 'non-cluster' headache (number of days and mean intensity per affected day)	12 weeks
Adverse events	Percentage of subjects with adverse-events (stratified for type of side effect (AE, SAE, SUSAR))	12 weeks
Subjective feeling	Subjective feeling at days 7, 14 and 28 (visual analogue scale, VAS. Scale from 0 to 10 where 0 is worst imaginable and 10 best imaginable)	Days 7, 14 and 28
Satisfaction score	Satisfaction score (7 point scale, 0 to 6. 0 is completely unsatisfied and 6 completely satisfied)	12 weeks
Recommendation	Would the patient recommend this treatment to others	Days 7, 14 and 28
Blinding participants	What treatment does the patient think he/she received (placebo/GON/uncertain)	Days 7, 14 and 28
Blinding investigators	What treatment do the investigators think the patient has had	Days 7, 14 and 28

Collaborators and Investigators

• Sponsor: Leiden University Medical Center
• Collaborators: Netherlands Brain Foundation; Innovatiefonds Zorgverzekeraars
• Investigators: Principal Investigator: Rolf Fronczek, MD, PhD, LUMC

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2019
• Primary Completion (Actual): August 27, 2021
• Study Completion (Actual): August 27, 2021

Study Registration Dates

• First Submitted: July 8, 2019
• First Submitted That Met QC Criteria: July 8, 2019
• First Posted (Actual): July 10, 2019

Study Record Updates

• Last Update Posted (Actual): March 13, 2024
• Last Update Submitted That Met QC Criteria: March 12, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Headache Disorders, Primary; Headache Disorders; Trigeminal Autonomic Cephalalgias; Headache; Cluster Headache; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Neuroprotective Agents; Protective Agents; Prednisolone; Methylprednisolone Acetate; Methylprednisolone; Methylprednisolone Hemisuccinate; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate
• Other Study ID Numbers: NL6719705818

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: All Data will be stored using Castor EDC. All hard copies will be stored in the individual centers. If requested, after study completion, data can be shared with de PIs in participating centers.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No