Treatment of Chronic Cluster Headache with TENS and ONS

NCT05023460 | Completed DMC FDA Device

• 1 other identifier: HortONS
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief Summary

The study is an investigator-initiated, prospective, randomized, placebo-controlled, double blind clinical trial that aims to investigate the effect of transcutaneous electrical nerve stimulation (TENS) and occipital nerve stimulation (ONS) on attack frequency and severity in patients with chronic cluster headache (CH). Study outline Month 1: Baseline. Establishment of a baseline profile of the participants CH attacks (severity, duration, medicine utilization etc), health-related quality of life (QoL) and symptoms of anxiety and depression. No active treatment. Follow-up visit after 30 days. Months 2-4: TENS period. All participants will receive TENS-treatment. Clinical follow-up visit by the end of month four. Months 5-7: Double-blinded, randomized experimental period. All participants will have an ONS-system (lead, impulse generator) implanted and will be randomized 1:1 to receive either 1) burst (paresthesia-free) ONS or 2) placebo (deactivated ONS system). Clinical follow-up visit by the end of month seven. Months 8-10: Open label period. All participants will receive tonic (conventional, paresthesia-inducing) ONS. Clinical follow-up visit by the end of month ten. During every study phase each participant will fill out a weekly electronic headache registration as well as answering questionnaires regarding health-related quality of life and symptoms of anxiety and depression before every follow-up visit.

Conditions

Chronic Cluster Headache; Primary Headache Disorder; Headache; Cluster Headache; Pain; Cephalgia; Trigeminal Autonomic Cephalgia

Keywords

Occipital nerve stimulation; Neuromodulation; Transcutaneous electrical nerve stimulation

Outcome Measures

Primary Outcomes (3)

• 30% reduction in CH attack frequency with TENS- and ONS-treatment

  Proportion of participants with a positive treatment outcome of a 30% reduction in CH attack frequency compared to baseline. A CH attack is here defined as any attack recognised by the patient as a CH attack.

  Primary evaluation through month 4 (TENS) and 7 (ONS, blinded)

• Incidence of treatment-emerged adverse events [safety] in TENS treatment

  Treatment related adverse events and adverse device effects will be registered on an ongoing basis. Serious events will be handled immediately.

  Evaluation at month 4

• Incidence of treatment-emerged adverse events [safety] in ONS treatment

  Treatment related adverse events and adverse device effects will be registered on an ongoing basis. Serious events will be handled immediately.

  Evaluation at month 7 (burst ONS) and 10 (tonic ONS)

Secondary Outcomes (8)

• 30% reduction of pain intensity in CH attacks

  Through month 4, 7 and 10

• Feasibility of TENS as a predictor for the efficacy of ONS treatment

  Through month 4 and 10

• Non-inferiority study: Burst ONS versus tonic ONS

  Through month 7 and 10

• Patient-perceived Global Impression of Change (PGIC)

  At month 4, 7 and 10

• Reduction in background headache

  At month 4, 7 and 10

Study Arms (2)

Paresthesia-free (burst) ONS

ACTIVE COMPARATOR

Implanted lead and impulse generator (IPG), paresthesia-free (burst) active stimulation. Lead implanted subcutaneously over greater occipital nerves. Implanted IPG capable of providing paresthesia-free stimulation continuously.

Device: Paresthesia-free (burst) ONS

Placebo

PLACEBO COMPARATOR

Implanted lead and IPG, deactivated.

Device: Placebo

Interventions

Paresthesia-free (burst) ONS DEVICE

Stimulation intensity target of 60% of paresthesia threshold.

Paresthesia-free (burst) ONS

Placebo DEVICE

ONS system deactivated

Placebo

Eligibility Criteria

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

You may qualify if:

• Age 18 years and above
• Signed informed written consent
• Diagnosed with chronic CH according to the ICHD-3 criteria
• or more CH attacks per month
• Stable use of preventive headache medication one month prior to enrollment

You may not qualify if:

• Other ongoing neuromodulation therapy
• Current alcohol and/or drug abuse
• Severe psychiatric disorder
• Other chronic primary or chronic secondary headache disorder (e.g. chronic migraine)
• Major posterior neck surgery in C2-C3 level and above
• Pregnancy
• Treatment with oral steroids or GON injection within one month of study participation

Sponsors & Collaborators

• University of Aarhus: lead
• Aarhus University Hospital: collaborator
• Danish Headache Center: collaborator

Study Sites (1)

Aarhus University Hospital

Aarhus N, 8200, Denmark

Location

Related Publications (2)

• Fogh-Andersen IS, Petersen AS, Jensen RH, Sorensen JCH, Meier K. Transcutaneous electrical nerve stimulation of the occipital nerves as treatment for chronic cluster headache. Headache. 2025 Jun;65(6):973-982. doi: 10.1111/head.14889. Epub 2024 Dec 20.

  PMID: 39703191 DERIVED

• Fogh-Andersen IS, Sorensen JCH, Petersen AS, Jensen RH, Meier K. The HortONS study. Treatment of chronic cluster headache with transcutaneous electrical nerve stimulation and occipital nerve stimulation: study protocol for a prospective, investigator-initiated, double-blinded, randomized, placebo-controlled trial. BMC Neurol. 2023 Oct 21;23(1):379. doi: 10.1186/s12883-023-03435-9.

  PMID: 37865755 DERIVED

MeSH Terms

Conditions

Cluster Headache; Headache Disorders, Primary; Headache; Pain; Trigeminal Autonomic Cephalalgias

Condition Hierarchy (Ancestors)

Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Ida S Fogh-Andersen, MD PhD fellow

  University of Aarhus

  PRINCIPAL INVESTIGATOR

• Kaare Meier, MD PhD

  University of Aarhus

  STUDY DIRECTOR

• Jens Christian H Sørensen, MD PhD DMSc

  University of Aarhus

  STUDY CHAIR

• Rigmor H Jensen, MD PhD DMSc

  Danish Headache Centre

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PhD fellow

Study Record Dates

• First Submitted: July 27, 2021
• First Posted: August 26, 2021
• Study Start: August 27, 2021
• Primary Completion: July 15, 2024
• Study Completion: July 31, 2024
• Last Updated: December 5, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)