A First-in-human Study to Assess the Initial Safety, Tolerability, and Effectiveness of the ONSS Bilateral Occipital Nerve Field Stimulation System for the Prophylactic Treatment of Chronic Cluster Headache in Difficult-to-treat Subjects. (ONFIELD)

A Monocentric, Single-arm, Single-blind Withdrawal First-in-human Study to Assess the Initial Safety, Tolerability, and Effectiveness of the ONSS Bilateral Occipital Nerve Field Stimulation System for the Prophylactic Treatment of Chronic Cluster Headache in Difficult-to-treat Subjects.

The purpose of this clinical trial is to evaluate the safety and effectiveness of the Occipital Nerve Stimulation System (ONSS) in treating chronic cluster headache in adults.

The study aims to answer the following questions:

• What adverse events or medical complications occur following ONSS implantation and stimulation?
• Does treatment with the ONSS reduce the frequency of cluster headache attacks compared with baseline?

Participant Involvement

Participants will:

• Undergo implantation of the ONSS device.
• Use the ONSS for a 48-week treatment period.
• Attend scheduled clinic visits for follow-up assessments and device evaluations.
• Maintain a diary documenting cluster headache attacks and use of rescue medications.
• Complete study-related assessments throughout the study period.

Study Overview

• Status: Recruiting
• Conditions: Chronic Cluster Headache
• Intervention / Treatment: Device: Occipital Nerve Stimulation System

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Christelle Nguepi; Phone Number: +34 613 581 071; Email: c.nguepi@manandscience.com

Study Locations

• Belgium
  • Sint-Niklaas, Belgium, 9100
    • Recruiting
    • Vitaz
    • Contact: Tamy Bonte; Phone Number: +32 3 760 2318; Email: pijncentrum@vitaz.be
    • Principal Investigator: Iris Smet, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. ICHD-3 criteria for chronic cluster headache
2. Documented history of CCH since at least 2 years
3. Minimum mean attack frequency of 4 attacks per week at baseline (-4week to +2 week up to implant)
4. Documented minimum 4 weeks of retrospective cluster headache diary data
5. Age range: 22-70 years
6. Difficult-to-treat CCH with documented previous complete failure, insufficient efficacy, intolerance, or contra-indications to most preventive CH treatments among which are oral steroids or suboccipital infiltrations, verapamil, lithium carbonate and topiramate.

7. No preventive CH treatment or stable preventive CH medication for ≥ 2 weeks before enrolment.

   Subject agrees not to change existing treatment during the whole duration of the trial.

8. Participant written informed consent provided before enrolment
9. Participant willing and capable of subjective evaluation and to fill in an electronic CH diary, to understand questionnaires, and to read, understand and sign the written informed consent form.
10. Partcipant willing and able to comply with study-related requirements, procedures, and visits.

Exclusion Criteria:

1. Other significant neurological, psychiatric, or disabling diseases which in the opinion of the investigator may interfere with the study.
2. History of epilepsy, current treatment of epilepsy
3. Documented history of cerebrovascular accident (CVA)
4. Participants suffering from a substance use disorder, as defined by Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria. Recreational use of cannabis is allowed.
5. Participants at high risk of suicide/suicidal ideation in the past one year assessed with the C-SSRS at screening
6. Having another active implanted device such as a cardiac pacemaker, a spinal cord, peripheral nerve, sphenopalatine ganglion, or deep brain hypothalamic stimulator, and/or a drug delivery pump, etc.
7. Cranial botulinum toxin injections in the past 3 months before enrolment. Administration of the following treatments in the last month before enrolment: monoclonal antibodies blocking calcitonin gene-related peptide transmission, suboccipital infiltrations with steroids and/or local anesthetics, oral steroids, radiofrequency procedure or infiltrations of the sphenopalatine ganglion, opioids WHO 3. Oral or systemic steroids are not allowed during the month before enrolment, except low doses (prednisone not superior to 10mg/day for no more than 7 days) if needed for other disorders.
8. Medication overuse headache (ICHD 3 8.2)
9. Inability to fill out an electronic diary.
10. Previous surgery or trauma involving the cervical spine or the occipital bone
11. Coagulopathy or required anticoagulant medications that cannot be safely discontinued in the perioperative period.
12. Concurrent participation in another clinical study
13. Planned pregnancy, pregnancy, or breastfeeding.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active treatment; Occipital nerve stimulation using the Occipital Nerve Stimulation System	Device: Occipital Nerve Stimulation System; 48 weeks of daily stimualtion with ONS System

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of procedure-related or device-related adverse events at 12 weeks	From implantation to 12 weeks post implantation
Number of adverse events at 48 weeks	From implantation to 48 weeks post-activation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the mean weekly attack frequency		From enrollment to 48 weeks post-activation
50% Responder rate	Proportion of subjects achieving a ≥ 50% reduction in mean weekly attack frequency compared to baseline	From enrollment to 48 weeks post-activation
30% Responder rate	Proportion of subjects achieving a ≥ 30% reduction in mean weekly attack frequency compared to baseline	From enrollment to 48 weeks post-activation
Change in the mean weekly attack intensity compared to baseline	Intensity is assessed using a 5-point ordinal pain scale from 0-no pain to 4-the worst pain	From enrollment to 48 weeks post-activation
Change in the mean number of weekly attack treatments compared to baseline	Attack treatments include but are not limited to triptan injections or nasal sprays or pills, 02 inhalations	From enrollment to 48 weeks post-activation
Scalp distribution of stimulation-induced paraesthesia per scalp region assessed using an 18-region scalp mapping tool	Scalp distribution of stimulation-induced paraesthesia will be assessed weekly and recorded in the participant's electronic diary. Participants will indicate the location(s) of perceived paraesthesia on a standardized scalp map divided into 18 predefined regions. The distribution will be quantified as the percentage of reported paraesthesia across these regions.	From enrollment to 48 weeks post-activation

Collaborators and Investigators

• Sponsor: Man and Science, SA

Study record dates

Study Major Dates

• Study Start (Actual): May 18, 2026
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2027

Study Registration Dates

• First Submitted: June 18, 2026
• First Submitted That Met QC Criteria: June 29, 2026
• First Posted (Actual): June 30, 2026

Study Record Updates

• Last Update Posted (Actual): June 30, 2026
• Last Update Submitted That Met QC Criteria: June 29, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Cluster Headaches
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Headache Disorders; Trigeminal Autonomic Cephalalgias; Cluster Headache
• Other Study ID Numbers: R-00179; CIV-26-02-056414 (Other Identifier: EUDAMED)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No