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

NCT04014634 | Completed Phase 4 DMC

• 1 other identifier: NL6719705818
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 6

Brief Summary

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.

Conditions

Cluster Headache, Episodic; Greater Occipital Nerve Injection

Outcome Measures

Primary Outcomes (1)

• Verapamil mean total dose

  Difference in mean total dose of verapamil used during the study period

  12 week period

Secondary Outcomes (4)

• Days to remission

  12 weeks

• Daily attacks

  12 weeks

• Peak dose verapamil

  12 weeks

• Preamature termination

  12 weeks

Other Outcomes (10)

• Use of attack medication

  12 weeks

• Daily attack severity and duration

  For the total study period and each of the three consecutive 4-week time periods

• Attack-freedom

  days 7, 14 and 28

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Injection of NaCl

Other: Placebo

Verum

EXPERIMENTAL

Drug: Methylprednisolone

Interventions

Methylprednisolone DRUG

Single GON injection with methylprednisolone

Verum

Placebo OTHER

Single GON-injection with NaCl

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Leiden University Medical Center: lead
• Netherlands Brain Foundation: collaborator
• Innovatiefonds Zorgverzekeraars: collaborator

Study Sites (6)

Boerhaave Clinics

Amsterdam, North Holland, Netherlands

Location

LUMC

Leiden, South Holland, Netherlands

Location

Alrijne Ziekenhuis

Leiderdorp, South Holland, Netherlands

Location

Tergooi Ziekenhuis

Blaricum, Netherlands

Location

Zuyderland Medisch Centrum

Heerlen, Netherlands

Location

Canisius-Wilhelmina Hospital

Nijmegen, Netherlands

Location

Related Publications (1)

• Brandt RB, Mulleners WM, Couturier E, Carpay JA, Gerlach OHH, Niesters M, Haan J, van Zwet EW, Ferrari MD, Fronczek R. Greater occipital nerve injection with methylprednisolone as transitional therapy in episodic cluster headache: Results from an RCT. Cephalalgia. 2025 Sep;45(9):3331024251370324. doi: 10.1177/03331024251370324. Epub 2025 Sep 24.

  PMID: 40990636 DERIVED

MeSH Terms

Conditions

Cluster Headache

Interventions

Methylprednisolone

Condition Hierarchy (Ancestors)

Trigeminal Autonomic Cephalalgias; Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Rolf Fronczek, MD, PhD

  LUMC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator

Study Record Dates

• First Submitted: July 8, 2019
• First Posted: July 10, 2019
• Study Start: August 1, 2019
• Primary Completion: August 27, 2021
• Study Completion: August 27, 2021
• Last Updated: March 13, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

NL (6)