Treatment of Chronic Cluster Headache with TENS and ONS (HortONS)

Treatment of Chronic Cluster Headache (Horton's Headache) with Transcutaneous Electrical Nerve Stimulation and Occipital Nerve Stimulation

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.

Study Overview

• Status: Completed
• Conditions: Pain; Headache; Cluster Headache; Chronic Cluster Headache; Primary Headache Disorder; Trigeminal Autonomic Cephalgia; Cephalgia
• Intervention / Treatment: Device: Paresthesia-free (burst) ONS; Device: Placebo

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Aarhus N, Denmark, 8200
    • Aarhus University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age 18 years and above
2. Signed informed written consent
3. Diagnosed with chronic CH according to the ICHD-3 criteria
4. 15 or more CH attacks per month
5. Stable use of preventive headache medication one month prior to enrollment

Exclusion Criteria:

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Paresthesia-free (burst) ONS; 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; Stimulation intensity target of 60% of paresthesia threshold.
Placebo Comparator: Placebo; Implanted lead and IPG, deactivated.	Device: Placebo; ONS system deactivated

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
30% reduction of pain intensity in CH attacks	Weekly self reported pain intensity on a numeric rating scale from 0-10 with 0 being "no pain" and 10 "the worst possible pain". Proportion of participants with a positive treatment outcome of a 30% reduction in pain intensity during CH attacks compared to baseline.	Through month 4, 7 and 10
Feasibility of TENS as a predictor for the efficacy of ONS treatment	Comparison will be made of headache data from the last month of treatment with TENS and tonic ONS, respectively, to evaluate whether a 30% reduction in CH attack duration with TENS-treatment correlates to a 30% reduction in CH attack duration with ONS-treatment.	Through month 4 and 10
Non-inferiority study: Burst ONS versus tonic ONS	Comparing treatment outcome of burst ONS and tonic ONS.	Through month 7 and 10
Patient-perceived Global Impression of Change (PGIC)	The number of participants who rates their condition 'much improved' or 'very much improved' as assessed by PGIC.	At month 4, 7 and 10
Reduction in background headache	Proportion of participants reporting a reduction in background headache. A positive treatment outcome will be defined as a two-point improvement on a four-point scale compared to baseline.	At month 4, 7 and 10
Hospital anxiety and depression scale (HADS)	HADS is a self-assessment questionnaire consisting of seven items each for depression and anxiety sub-scales. Scoring for each item ranges from zero to three, with three denoting highest anxiety or depression level. HADS score will be evaluated at every follow up and compared to baseline.	At month 4, 7 and 10
Health-related quality of life (EuroQoL 5D-5L)	The EQ 5D-5L is a well-established measure of health-related quality of life that is quantified as a utility (a measure of quality of life between 0 and 1) based on a danish value set. Furthermore a total score that ranges from 0-100 (visual analog scale), a higher score indicates better health-related quality of life.	At month 4, 7 and 10
Self reported sleep quality	Proportion af participants reporting a positive treatment outcome defined as a two-point improvement on a four-point scale compared to baseline.	At month 4, 7 and 10

Collaborators and Investigators

• Sponsor: University of Aarhus
• Collaborators: Danish Headache Center; Aarhus University Hospital
• Investigators: Principal Investigator: Ida S Fogh-Andersen, MD PhD fellow, University of Aarhus; Study Director: Kaare Meier, MD PhD, University of Aarhus; Study Chair: Jens Christian H Sørensen, MD PhD DMSc, University of Aarhus; Study Chair: Rigmor H Jensen, MD PhD DMSc, Danish Headache Centre

Study record dates

Study Major Dates

• Study Start (Actual): August 27, 2021
• Primary Completion (Actual): July 15, 2024
• Study Completion (Actual): July 31, 2024

Study Registration Dates

• First Submitted: July 27, 2021
• First Submitted That Met QC Criteria: August 20, 2021
• First Posted (Actual): August 26, 2021

Study Record Updates

• Last Update Posted (Estimated): December 5, 2024
• Last Update Submitted That Met QC Criteria: December 3, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: Neuromodulation; Transcutaneous electrical nerve stimulation; Occipital nerve stimulation
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders; Headache; Cluster Headache; Headache Disorders, Primary; Trigeminal Autonomic Cephalalgias
• Other Study ID Numbers: HortONS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes