Repeated GON Injections in CCH

Study Overview
=================
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.

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

Conditions
-----------------
Cluster Headache

Intervention / Treatment
-----------------
* Drug: Methylprednisolone
* Drug: Saline solution


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Bi-centre, randomized, double-blind, placebo-controlled retention trial
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo Arm<br> | Drug: Saline solution<br>* 0,9%<br>|
| Experimental: Intervention Arm<br> | Drug: Methylprednisolone<br>* Injection with prednisolon<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| Adverse events |  | 1 year | 
| Ultrasound structural integrity of the greater occipital nerve |  | 1 year | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
GON-injection