Repeated GON Injections in CCH (REGON)

Repeated Corticosteroid Injections Around the Greater Occipital Nerve (GON) as Prophylactic Treatment in Chronic Cluster Headache

Background:

- The effect of repeated GON-injections has never been studied in a double-blind randomized trial as a prophylactic therapy in a well-documented group of chronic patients. As such, (repeated) GON-injection has not yet found its place in current (inter)national treatment protocols for chronic cluster headache.

Objectives:

- The primary objective is to determine if repeated GON-injection result in effective control of cluster headache attacks for more days compared to placebo in chronic cluster headache.

Eligibility:

- Patients will be selected from the LUMC (Leiden University Medical Center) and CWZ (Canisius Wilhelmina Hospital) chronic cluster headache populations, diagnosed based upon the ICHD-3.

Design:

- Bi-centre, randomized, double-blind, placebo-controlled retention trial with a maximum follow-up of one year.

Study Overview

• Status: Recruiting
• Conditions: Cluster Headache
• Intervention / Treatment: Drug: Saline solution; Drug: Methylprednisolone

Detailed Description

A single injection of the greater occipital nerve (GON) with corticosteroids ('GON-injection') has been shown to be efficacious for the prophylactic treatment of cluster headache, with only mild, local side effects and often has its effect within days. It is a low-cost and safe treatment option; however, the beneficial effects are limited to weeks to months. This makes the injection suitable for episodic cluster headache, where periods with headache attacks last weeks to months. However, the effect of repeated GON-injections has never been studied in a double-blind randomized trial as a prophylactic therapy in a well-documented group of chronic patients. As such, (repeated) GON-injection has not yet found its place in current (inter)national treatment protocols for chronic cluster headache. The injection is often only used as a last-resort treatment in a very limited number of headache centres in a trial-and-error approach with a treatment interval varying between 3 and 6 months. It is, therefore, not known what chronic cluster headache patients can expect from this treatment.

Hypothesis: Repeated GON-injections are a safe, well-tolerated, convenient, and cost-effective therapy to rapidly and long-term reduce the attack frequency in chronic cluster headache.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Willemijn Naber; Phone Number: 0715262587; Email: w.c.naber@lumc.nl

Study Locations

• Netherlands
  • Leiden, Netherlands
    • Recruiting
    • Leiden University Medical Center
    • Contact: Willemijn Naber
  • Nijmegen, Netherlands
    • Recruiting
    • Canisius Wilhelmina Ziekenhuis
    • Contact: Wim Mulleners

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥18 and ≤ 70 years
• Chronic cluster headache (International Classification of Headache Disorders - third edition; ICHD-3)
• Ictal pain must be always at the same side
• ≥4 weekly attacks of cluster headache in the prospective one-month baseline observation period
• On a stable regimen of cluster headache prophylactics for >4 weeks prior to onset of study treatment and agreeing not to increase the dose and not starting a new cluster prophylactic during the study period

Exclusion Criteria:

• Contra-indication against, or current use of, corticosteroids
• Occipital nerve stimulation (ONS)
• Use of anticoagulation medication or a known bleeding disorder
• Inability to use an electronic diary to monitor individual attacks and other items
• Other headaches if the patient cannot reliably distinguish them from attacks of cluster headache
• Current use of prophylactic medication for other headaches
• 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: Intervention Arm	Drug: Methylprednisolone; Injection with prednisolon
Placebo Comparator: Placebo Arm	Drug: Saline solution; 0,9%

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
mean number of days, from first injection until discontinuation, study participants remain using study medication (retention rate in survival curve)	1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
Adverse events	1 year
Frequency of weekly cluster headache attacks vs. baseline	1 year
Mean duration of attacks vs. baseline	1 year
Mean severity (1-10) of attacks vs. baseline	1 year
Proportion of study participants with >50% or 100% reduction in attack frequency vs. baseline	1 year
Median injection interval	1 year
Ultrasound structural integrity of the greater occipital nerve	1 year

Collaborators and Investigators

• Sponsor: Leiden University Medical Center
• Collaborators: ZonMw: The Netherlands Organisation for Health Research and Development

Study record dates

Study Major Dates

• Study Start (Actual): November 7, 2022
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: April 5, 2022
• First Submitted That Met QC Criteria: April 5, 2022
• First Posted (Actual): April 12, 2022

Study Record Updates

• Last Update Posted (Actual): November 24, 2025
• Last Update Submitted That Met QC Criteria: November 19, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: GON-injection
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Headache Disorders; Trigeminal Autonomic Cephalalgias; Cluster Headache; Pharmaceutical Preparations; Polycyclic Compounds; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Crystalloid Solutions; Isotonic Solutions; Solutions; Pregnadienetriols; Prednisolone; Methylprednisolone; Saline Solution
• Other Study ID Numbers: 79665

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