Cluster HeadachePhase 3REGONNCT05324748
Repeated GON Injections in CCH
A Phase 3 study testing Methylprednisolone and Saline solution in people with Cluster Headache, run by Leiden University Medical Center at 2 sites in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Cluster Headache
- What is being tested?
- Methylprednisolone and Saline solution
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 2 sitesNetherlands
- Study dates
- 7 Nov 2022to Jun 2026
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Netherlands2 sites, 2 recruiting
- Recruiting
Leiden University Medical Center
Leiden
Willemijn Naber
- Recruiting
Canisius Wilhelmina Ziekenhuis
Nijmegen
Wim Mulleners
About this study
Official title: 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.
Read more
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.
Read the 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.
- Conditions
- Cluster Headache
- Being tested
- Methylprednisolone, Saline solution
- Keywords
- GON-injection
- Medical subject headings
- Cluster Headache
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Injection with prednisolon
Saline solutionDrug
0,9%
| Study group | Role | What they receive |
|---|---|---|
| Placebo Arm | Placebo comparator | Not described Receives: Drug: Saline solution |
| Intervention Arm | Experimental | Not described Receives: Drug: Methylprednisolone |
What is being measured
The primary outcome is the main question the study is designed to answer.
mean number of days, from first injection until discontinuation, study participants remain using study medication (retention rate in survival curve)
Measured: 1 year
Secondary outcomes (7)
Frequency of weekly cluster headache attacks vs. baseline
Measured: 1 year
Mean duration of attacks vs. baseline
Measured: 1 year
Mean severity (1-10) of attacks vs. baseline
Measured: 1 year
Proportion of study participants with >50% or 100% reduction in attack frequency vs. baseline
Measured: 1 year
Median injection interval
Measured: 1 year
Adverse events
Measured: 1 year
Ultrasound structural integrity of the greater occipital nerve
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Apr 2022
- Study start7 Nov 2022
- Primary completionDec 2025 (estimated)
- Study completionJun 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cluster HeadacheStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Bi-centre, randomized, double-blind, placebo-controlled retention trial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Leiden University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- ZonMw: The Netherlands Organisation for Health Research and Development
- Responsible party
- Principal investigator, Rolf Fronczek, Leiden University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05324748
- Sponsor's protocol ID
- 79665
- Acronym
- REGON
- Status last verified
- Feb 2025
- First submitted
- 5 Apr 2022
- Last updated
- 24 Nov 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Repeated Corticosteroid Injections Around the Greater Occipital Nerve (GON) as Prophylactic Treatment in Chronic Cluster Headache
- ClinicalTrials.gov ID
- NCT05324748
- Acronym / sponsor ID
- REGON / 79665
- Conditions
- Cluster Headache
- Keywords
- GON-injection
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Leiden University Medical CenterUniversity, hospital or other
- Collaborators
- ZonMw: The Netherlands Organisation for Health Research and Development
- Study start
- 7 Nov 2022 (actual)
- Primary completion
- Dec 2025 (estimated)
- Study completion
- Jun 2026 (estimated)
- First posted
- 12 Apr 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Bi-centre, randomized, double-blind, placebo-controlled retention trial
| Arm | Type | Receives |
|---|---|---|
| Placebo Arm | Placebo comparator | Drug: Saline solution |
| Intervention Arm | Experimental | Drug: Methylprednisolone |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MethylprednisoloneInjection with prednisolon | Drug | Intervention Arm |
| Saline solution0,9% | Drug | Placebo Arm |
Primary outcome
mean number of days, from first injection until discontinuation, study participants remain using study medication (retention rate in survival curve)
Time frame: 1 year
7 secondary outcomes
Frequency of weekly cluster headache attacks vs. baseline
Time frame: 1 year
Mean duration of attacks vs. baseline
Time frame: 1 year
Mean severity (1-10) of attacks vs. baseline
Time frame: 1 year
Proportion of study participants with >50% or 100% reduction in attack frequency vs. baseline
Time frame: 1 year
Median injection interval
Time frame: 1 year
Adverse events
Time frame: 1 year
Ultrasound structural integrity of the greater occipital nerve
Time frame: 1 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Nov 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Methylprednisolone and Saline solution in people with Cluster Headache, run by Leiden University Medical Center at 2 sites in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 24 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Willemijn Naber (0715262587, w.c.naber@lumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
mean number of days, from first injection until discontinuation, study participants remain using study medication (retention rate in survival curve) (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Nov 2025.