Repeated GON Injections in CCH

Phase 3

Recruiting

• Conditions: Cluster Headache
• Interventions: Drug: Saline solution; Drug: Methylprednisolone

• Registration Number: NCT05324748
• Lead Sponsor: Leiden University Medical Center

Brief Summary

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.

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 Timeline

• Study First Submitted: 2022-04-05
• Study First Submitted QC: 2022-04-05
• Study First Posted: 2022-04-12
• Study Start: 2022-11-07
• Status Verified: 2023-12
• Last Update Submitted: 2023-12-19
• Last Update Posted: 2023-12-26
• Primary Completion: 2024-12
• Study Completion: 2024-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 50

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo Arm	Saline solution	-
Intervention Arm	Methylprednisolone	-

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
Median injection interval	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
Ultrasound structural integrity of the greater occipital nerve	1 year
Frequency of weekly cluster headache attacks vs. baseline	1 year
Adverse events	1 year

Trial Locations

Locations (2)

Leiden University Medical Center; 🇳🇱 Leiden, Netherlands

Canisius Wilhelmina Ziekenhuis; 🇳🇱 Nijmegen, Netherlands