Chronic Cluster HeadachePhase 3ICONNCT01151631
Occipital Nerve Stimulation in Medically Intractable Chronic Cluster Headache
A Phase 3 study testing occipital nerve stimulation in people with Chronic Cluster Headache, run by Leiden University Medical Center at 7 sites in 4 countries.
Trial summary
Cluster headache (CH) is a primary headache disorder characterized by recurrent short-lasting attacks (15 to 180 minutes) of excruciating unilateral periorbital pain accompanied by ipsilateral cranial autonomic signs. The 1-year prevalence of CH is about 0.1 %, the male: female ratio is 3:1. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Cluster Headache
- What is being tested?
- occipital nerve stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 130 participants
- Where
- 7 sitesin 4 countries
- Study dates
- Oct 2010to Mar 2019
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of patients with CH shall be in accordance with The International Classification of Headache Disorders, 2nd Edition:
- At least 5 attacks fulfilling criteria B-D B. Severe or very severe unilateral orbital, supraorbital and/or temporal pain lasting 15-180 minutes if untreated
- Headache is accompanied by at least 1 of the following:
- ipsilateral conjunctival injection and/or lacrimation
- ipsilateral nasal congestion and/or rhinorrhoea
- ipsilateral eyelid oedema
Show all 30Show fewer
- ipsilateral forehead and facial sweating
- ipsilateral miosis and/or ptosis
- a sense of restlessness or agitation D. Attacks have a frequency from 1 every other day to 8 per day E. Not attributed to another disorder
- Chronic cluster headache A. Attacks fulfilling criteria A-E for Cluster headache B. Attacks recur over >1 year without remission periods or with remission periods lasting <1 month
- ICHD-II criteria for CCH (see above)
- Minimum mean attack frequency of 4 attacks per week
- Minimum age of 18 years old
- Signed study specific informed consent form
- Agreeing to refrain from starting new prophylactic CH medication, including steroids, or any other therapy aimed at CH and agrees to maintain existing prophylactic CH medication from 4 weeks before entering the baseline period throughout the duration of the double blind phase of the study. It is allowed to change the dose of prophylactic medication during the study based on the opinion of the treating medical specialist.
- Availability during follow-up period
- An MRI to exclude structural lesions potentially causing CCH.
- Medically intractable (see below)
- Definition medically intractable :
- Failed adequate trials of regulatory approved and conventional treatments according to local national guidelines
- Adequate trial:
- Appropriate dose and duration of treatment according to local guidelines Appropriate length of time Consideration of medication overuse
- Failed:
- No therapeutic or unsatisfactory effect, intolerable side effects, contraindications to use
- Must have tried agents of at least three classes of the following, of which 1 and 2 are obligatory, and 1 should come from 3-5: (recommendation of Goadsby et al. applied to Dutch national guidelines)
- Verapamil
- Lithium
- Methysergide
- Topiramate
- Gabapentin
Who cannot join
- Other significant neurological or disabling diseases which in the opinion of the clinician may interfere with the study
- Pregnancy or the wish to become pregnant during the study period
- Cardiac pacemaker and other neuromodulatory devices
- Psychiatric or cognitive disorders and/or behavioural problems which in the opinion of the clinician may interfere with the study
- Taking CH prophylactic medication for conditions other than CH which in the opinion of the clinician may interfere with the study
- Serious drug habituation and/or overuse of acute headache medication for other headaches than CH
Show all 11Show fewer
- Inability to complete the (electronic) diary in a sensible and accurate manner
- Structural intracranial or cervical vascular lesions that may potentially cause CH
- Previous destructive surgery involving the C2 or C3 roots (vertebrae) or deep brain stimulation
- Enrollment in other clinical studies that may confound the results of this study
- Requiring anticoagulation therapy or antithrombotic or thrombocyte aggregation-inhibitor for a concomitant condition that cannot be stopped peri-operatively. The local peri-operative protocol of each individual participating centre will be followed
Trial locations and contacts
7 sites in 4 countries.
7 sites in 4 countries
Netherlands4 sites
Boerhaave MC
Amsterdam
Atrium medical centre
Heerlen, 6417
Leiden University Medical Center
Leiden, 2333 ZA
Canisius Wilhelmina Hospital
Nijmegen, 6532 SZ
About this study
Cluster headache (CH) is a primary headache disorder characterized by recurrent short-lasting attacks (15 to 180 minutes) of excruciating unilateral periorbital pain accompanied by ipsilateral cranial autonomic signs. The 1-year prevalence of CH is about 0.1 %, the male: female ratio is 3:1. The majority of patients have cluster periods of weeks to months with frequent attacks which are alternated with symptom-free periods of months to several years; the episodic from of CH. In about 10% of patients the CH is chronic (CCH) in which either no remission occurs within 1 year or the remissions last less than 1 month. At least 10 % of CCH patients are refractory to medical treatment or cannot tolerate the treatments.
Recent pilot studies suggest that occipital nerve stimulation (ONS) in medically intractable CCH (MICCH) might offer an effective alternative to medical treatment. There are no randomised clinical trials and a placebo effect cannot be excluded. Long term tolerability is known from other indications.
Read more
Here the investigators propose a prospective, randomised, double blind, parallel group multi-centre international clinical study to compare the reduction in attack frequency from baseline of occipital nerve stimulation (ONS) in patients with MICCH between two different stimulation conditions: high (100%) and low (30%) stimulation.
Following implantation there will first be a run-in phase of 10 days of 10% stimulation intensity, followed by a stepwise monthly increase up to either 30% or 100%. Patients will be assessed monthly by a blinded assessor. The primary outcome measure is the mean number of attacks over the last 4 weeks of the double blind 6 month treatment period in the 100% versus the 30% treatment group. Hereafter, in an open extension phase of 6 months, all patients will receive 100% stimulation or the stimulation considered optimal by the patient.
Secondary outcome measures include the rate of responders (≥ 50% reduction in attack frequency during the last 4 weeks of each treatment period), patient's satisfaction, medication use, quality of life, mean pain intensity, economic evaluation and whether patients would recommend the treatment to another patient. The investigators will also investigate whether predictive factors can be identified for efficacy.
Read the detailed description
Trigeminal autonomic cephalalgias (TACs) are characterized by frequent, short-lasting attacks of unilateral extremely severe headaches accompanied by ipsilateral facial autonomic features and are the most severe of the primary headache disorders. TACs include cluster headache (CH), paroxysmal hemicrania (PH) and short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT). CH is the most common form of TAC. The 1-year prevalence is about 1 in 1000, with the vast majority of patients having episodic CH (ECH): periods of weeks to months with frequent attacks which are alternated with symptom-free periods of several months to years. About 10% have chronic CH (CCH): attack free periods of less than one month in every 12 months, unless treatment is given. The chronic form can be primary unremitting from onset, or can be secondary, transform from the episodic form. CCH may spontaneously become episodic.
Effective acute treatments for CH attacks are injectable or intranasal triptans and oxygen inhalation. Steroids (only for a short period), verapamil, lithium carbonate and methysergide are the most effective preventive therapies. At least 10% of patients with CCH is or may become refractory to or cannot tolerate medical therapy. For patients with medically intractable CCH (MICCH) there is no common treatment. Different experimental treatments, such as deep brain stimulation (DBS), radiofrequency lesions, glycerol injections, gamma knife, and surgery or root section of the trigeminal nerve are either substantially ineffective, or have significant short-comings with serious complications such as death or neurological deficits such as anaesthesia dolorosa or lack of efficacy.
CH has considerable impact on socio-economic and personal functions due to direct costs of healthcare services and indirect costs of lost work days and decreased work efficacy. Higher pain scores and a higher percentage of patients with poor health due to pain and social functioning are found among CH patients compared with patients suffering from migraine. The impact on social functions, quality of life and use of healthcare of patients with MICCH is most likely even larger, although precise figures are not available. In the study of Burns et al. patients, suffering from MICCH, had on average over four attacks per day. Attacks of CH have been described by patients as being worse than child birth. Recently treatment of headache was listed as one of the top priorities of US National the Institute of Medicine's agenda for comparative-effectiveness research.
Functional imaging studies in CH identified activations in the region of the posterior hypothalamus, which led to the use of neurostimulation therapy in MICCH. Hypothalamic DBS was shown to be effective in some patients with MICCH but unfortunately this treatment is associated with a high risk of (even lethal) consequences.
Structures in the occipital region of the head are mainly innervated by the greater occipital nerve that is a branch of the C2 spinal root. Convergence of cervical, somatic trigeminal and dural trigeminovascular afferents on second order nociceptors in the brain stem is well documented. Stimulation of the greater occipital nerve increased metabolic activity in cervical regions of the spinal cord and in the trigeminal nucleus caudalis in the cat. In humans an occipital nerve blockade decreased the ipsi- and contralateral R2 response, confirming the anatomic and functional convergence of afferent cervical and trigeminal pathways. These studies suggest that modulation of these pathways may influence headache.
Suboccipital injection of corticosteroid with local anaesthetics was shown to be effective in a placebo-controlled trial. In this study 4 patients suffering from CCH were included. In all patients the attacks recurred eventually. The authors suggest that suboccipital steroid injections ought to be tried as a single shot treatment before invasive treatments are considered such as DBS, but in later studies this turned out to be of no predictive value of the response to neuromodulation therapies.
Along the same line, stimulation of the greater occipital nerve (ONS) has been tried with some success in intractable headaches including CCH. Burns et al. described 14 patients suffering from MICCH and were treated with ONS in an open retrospective study. Ten patients improved; three improved by 90% or more, 3 by 40%-90% and 4 by 20-30%. In a prospective open ONS study on MICCH patients Magis et al. showed a reduction in attack frequency of 79.9%. No serious complications were described in both studies.
- Conditions
- Chronic Cluster Headache
- Being tested
- occipital nerve stimulation
- Medical subject headings
- Cluster Headache
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
occipital nerve stimulationDevice
Also called Versitrel™, Pisces Quad® Plus, Versitrel™ Patient Programmer
Low occipital bilateral Quad Plus, midline to laterally directed, secured by titan anchors, connected to Versitrel. No trial stimulation. Suggested stimulation parameters: Pulse width: 450, Amplitude: protocol, Rate: 60
| Study group | Role | What they receive |
|---|---|---|
| 100% occipital nerve stimulation | Active comparator | Stimulation frequency and pulse width will be uniformly held constant at 60 Hz and pulse width at 450 ms. The perception and discomfort amplitude will be defined by increasing the stimulation amplitude in steps of 0.1 V. The amplitude at which the patient starts feeling paraesthesis is called the perception threshold. The threshold at which the patient does not want the voltage to be increased any further because of painful sensations is designated the discomfort threshold. 100% stimulation is defined as stimulation at 90% of the range between perception and discomfort thresholds. Receives: Device: occipital nerve stimulation |
| 30% occipital nerve stimulation | Sham comparator | 30% stimulation means a stimulation level at 30% of the range between perception threshold and 100% stimulation level Receives: Device: occipital nerve stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
The mean attack frequency (MAF) over the last 4 weeks in the 100% and the 30% treatment groups
An attack is defined as any attack recognised by the patient as being a CH attack. So also the attacks treated with oxygen or triptans.
Measured: 6 months
Secondary outcomes (11)
The MAF during follow up
Measured: for each 4 week period of the whole follow-up period
The mean attack intensity (on a scale from 0-10) will be calculated and will be compared between and within the 2 groups.
Measured: over the last 4 weeks for each group at baseline, 6 and 12 months follow up
Rate of responders (>50% reduction in attack frequency in the last 4 weeks compared to baseline) will be calculated and compared between groups
Measured: 6 and 12 months follow up
Economic evaluation
Measured: baseline and 6 months follow-up
Anticipated group randomisation
Measured: at 12 months follow-up
Awareness of paraesthesias
Measured: weekly during 6 months follow up
The use of acute attack medication
Measured: during the last 4 weeks at baseline periode and 6 months follow up
Patient satisfaction
The investigators will ask the patient whether he/she would recommend the treatment to another patient using a 5 point (Likert) scale: Strongly disagree, disagree, neither agree nor disagree, agree, strongly agree.
Measured: 6 and 12 months follow up
Responder identification
It is also investigated whether predictive factors can be identified with respect to the outcome in a hypothesis generating manner. We will look at the body mass index (BMI) and assess the predictive value of response after 5-7 days.
Measured: 12 months follow up
Adverse events
All and treatment-related adverse events will be documented by the investigators.
Measured: 1 year
MAF
MAF: We will repeat the primary analysis, with the MAF as outcome instead of the logarithm of the MAF.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jun 2010 (estimated)
- Study startOct 2010
- Primary completionSep 2018
- Study completionMar 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Chronic Cluster HeadacheStudies of the same condition, open and under way.
- More trials run by Leiden University Medical CenterThe sponsor's other registered studies.
- 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
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 130 participants (actual)
Sponsor and investigators
- Lead sponsor
- Leiden University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Maastricht University Medical Center, Erasmus Medical Center, Technical University of Twente, Canisius-Wilhelmina Hospital, University of Copenhagen, University Hospital, Ghent, Royal Free Hospital NHS Foundation Trust, Medtronic, Centre Hospitalier Régional de la Citadelle, Kiel Pain Clinic, University Hospital Schleswig-Holstein, National Institute of Neuroscience, Budapest
- Responsible party
- Principal investigator, MDFerrari, Leiden University Medical Center
- Investigators
- Michel Ferrari, MD PhD, Principal investigator, Leiden University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01151631
- Sponsor's protocol ID
- ICON-01
- Acronym
- ICON
- Status last verified
- Feb 2020
- First submitted
- 24 Jun 2010
- Last updated
- 28 Feb 2020
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Burns B, Watkins L, Goadsby PJ. Treatment of intractable chronic cluster headache by occipital nerve stimulation in 14 patients. Neurology. 2009 Jan 27;72(4):341-5. doi: 10.1212/01.wnl.0000341279.17344.c9.
PubMed 19171831Burns B, Watkins L, Goadsby PJ. Treatment of medically intractable cluster headache by occipital nerve stimulation: long-term follow-up of eight patients. Lancet. 2007 Mar 31;369(9567):1099-106. doi: 10.1016/S0140-6736(07)60328-6.
PubMed 17398309Magis D, Allena M, Bolla M, De Pasqua V, Remacle JM, Schoenen J. Occipital nerve stimulation for drug-resistant chronic cluster headache: a prospective pilot study. Lancet Neurol. 2007 Apr;6(4):314-21. doi: 10.1016/S1474-4422(07)70058-3.
PubMed 17362835Brandt RB, Mulleners W, Wilbrink LA, Brandt P, van Zwet EW, Huygen FJ, Ferrari MD, Fronczek R; ICON study group. Intra- and interindividual attack frequency variability of chronic cluster headache. Cephalalgia. 2023 Feb;43(2):3331024221139239. doi: 10.1177/03331024221139239.
PubMed 36739508Wilbrink LA, de Coo IF, Doesborg PGG, Mulleners WM, Teernstra OPM, Bartels EC, Burger K, Wille F, van Dongen RTM, Kurt E, Spincemaille GH, Haan J, van Zwet EW, Huygen FJPM, Ferrari MD; ICON study group. Safety and efficacy of occipital nerve stimulation for attack prevention in medically intractable chronic cluster headache (ICON): a randomised, double-blind, multicentre, phase 3, electrical dose-controlled trial. Lancet Neurol. 2021 Jul;20(7):515-525. doi: 10.1016/S1474-4422(21)00101-0.
PubMed 34146510
Study at a glance
From the registry record, last updated by the sponsor on 28 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Occipital Nerve Stimulation in Medically Intractable Chronic Cluster Headache
- ClinicalTrials.gov ID
- NCT01151631
- Acronym / sponsor ID
- ICON / ICON-01
- Conditions
- Chronic Cluster Headache
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 130 participants (actual)
- Lead sponsor
- Leiden University Medical CenterUniversity, hospital or other
- Collaborators
- Maastricht University Medical Center, Erasmus Medical Center, Technical University of Twente, Canisius-Wilhelmina Hospital, University of Copenhagen, University Hospital, Ghent, Royal Free Hospital NHS Foundation Trust, Medtronic, Centre Hospitalier Régional de la Citadelle, Kiel Pain Clinic, University Hospital Schleswig-Holstein, National Institute of Neuroscience, Budapest
- Study start
- Oct 2010
- Primary completion
- Sep 2018 (actual)
- Study completion
- Mar 2019 (actual)
- First posted
- 28 Jun 2010 (estimated)
- 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.
Cluster headache (CH) is a primary headache disorder characterized by recurrent short-lasting attacks (15 to 180 minutes) of excruciating unilateral periorbital pain accompanied by ipsilateral cranial autonomic signs. The 1-year prevalence of CH is about 0.1 %, the male: female ratio is 3:1. The majority of patients have cluster periods of weeks to months with frequent attacks which are alternated with symptom-free periods of months to several years; the episodic from of CH. In about 10% of patients the CH is chronic (CCH) in which either no remission occurs within 1 year or the remissions last less than 1 month. At least 10 % of CCH patients are refractory to medical treatment or cannot tolerate the treatments.
Recent pilot studies suggest that occipital nerve stimulation (ONS) in medically intractable CCH (MICCH) might offer an effective alternative to medical treatment. There are no randomised clinical trials and a placebo effect cannot be excluded. Long term tolerability is known from other indications.
Here the investigators propose a prospective, randomised, double blind, parallel group multi-centre international clinical study to compare the reduction in attack frequency from baseline of occipital nerve stimulation (ONS) in patients with MICCH between two different stimulation conditions: high (100%) and low (30%) stimulation.
Following implantation there will first be a run-in phase of 10 days of 10% stimulation intensity, followed by a stepwise monthly increase up to either 30% or 100%. Patients will be assessed monthly by a blinded assessor. The primary outcome measure is the mean number of attacks over the last 4 weeks of the double blind 6 month treatment period in the 100% versus the 30% treatment group. Hereafter, in an open extension phase of 6 months, all patients will receive 100% stimulation or the stimulation considered optimal by the patient.
Secondary outcome measures include the rate of responders (≥ 50% reduction in attack frequency during the last 4 weeks of each treatment period), patient's satisfaction, medication use, quality of life, mean pain intensity, economic evaluation and whether patients would recommend the treatment to another patient. The investigators will also investigate whether predictive factors can be identified for efficacy.
Detailed description
Trigeminal autonomic cephalalgias (TACs) are characterized by frequent, short-lasting attacks of unilateral extremely severe headaches accompanied by ipsilateral facial autonomic features and are the most severe of the primary headache disorders. TACs include cluster headache (CH), paroxysmal hemicrania (PH) and short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT). CH is the most common form of TAC. The 1-year prevalence is about 1 in 1000, with the vast majority of patients having episodic CH (ECH): periods of weeks to months with frequent attacks which are alternated with symptom-free periods of several months to years. About 10% have chronic CH (CCH): attack free periods of less than one month in every 12 months, unless treatment is given. The chronic form can be primary unremitting from onset, or can be secondary, transform from the episodic form. CCH may spontaneously become episodic.
Effective acute treatments for CH attacks are injectable or intranasal triptans and oxygen inhalation. Steroids (only for a short period), verapamil, lithium carbonate and methysergide are the most effective preventive therapies. At least 10% of patients with CCH is or may become refractory to or cannot tolerate medical therapy. For patients with medically intractable CCH (MICCH) there is no common treatment. Different experimental treatments, such as deep brain stimulation (DBS), radiofrequency lesions, glycerol injections, gamma knife, and surgery or root section of the trigeminal nerve are either substantially ineffective, or have significant short-comings with serious complications such as death or neurological deficits such as anaesthesia dolorosa or lack of efficacy.
CH has considerable impact on socio-economic and personal functions due to direct costs of healthcare services and indirect costs of lost work days and decreased work efficacy. Higher pain scores and a higher percentage of patients with poor health due to pain and social functioning are found among CH patients compared with patients suffering from migraine. The impact on social functions, quality of life and use of healthcare of patients with MICCH is most likely even larger, although precise figures are not available. In the study of Burns et al. patients, suffering from MICCH, had on average over four attacks per day. Attacks of CH have been described by patients as being worse than child birth. Recently treatment of headache was listed as one of the top priorities of US National the Institute of Medicine's agenda for comparative-effectiveness research.
Functional imaging studies in CH identified activations in the region of the posterior hypothalamus, which led to the use of neurostimulation therapy in MICCH. Hypothalamic DBS was shown to be effective in some patients with MICCH but unfortunately this treatment is associated with a high risk of (even lethal) consequences.
Structures in the occipital region of the head are mainly innervated by the greater occipital nerve that is a branch of the C2 spinal root. Convergence of cervical, somatic trigeminal and dural trigeminovascular afferents on second order nociceptors in the brain stem is well documented. Stimulation of the greater occipital nerve increased metabolic activity in cervical regions of the spinal cord and in the trigeminal nucleus caudalis in the cat. In humans an occipital nerve blockade decreased the ipsi- and contralateral R2 response, confirming the anatomic and functional convergence of afferent cervical and trigeminal pathways. These studies suggest that modulation of these pathways may influence headache.
Suboccipital injection of corticosteroid with local anaesthetics was shown to be effective in a placebo-controlled trial. In this study 4 patients suffering from CCH were included. In all patients the attacks recurred eventually. The authors suggest that suboccipital steroid injections ought to be tried as a single shot treatment before invasive treatments are considered such as DBS, but in later studies this turned out to be of no predictive value of the response to neuromodulation therapies.
Along the same line, stimulation of the greater occipital nerve (ONS) has been tried with some success in intractable headaches including CCH. Burns et al. described 14 patients suffering from MICCH and were treated with ONS in an open retrospective study. Ten patients improved; three improved by 90% or more, 3 by 40%-90% and 4 by 20-30%. In a prospective open ONS study on MICCH patients Magis et al. showed a reduction in attack frequency of 79.9%. No serious complications were described in both studies.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 100% occipital nerve stimulation | Active comparator | Device: occipital nerve stimulationStimulation frequency and pulse width will be uniformly held constant at 60 Hz and pulse width at 450 ms. The perception and discomfort amplitude will be defined by increasing the stimulation amplitude in steps of 0.1 V. The amplitude at which the patient starts feeling paraesthesis is called the perception threshold. The threshold at which the patient does not want the voltage to be increased any further because of painful sensations is designated the discomfort threshold. 100% stimulation is defined as stimulation at 90% of the range between perception and discomfort thresholds. |
| 30% occipital nerve stimulation | Sham comparator | Device: occipital nerve stimulation30% stimulation means a stimulation level at 30% of the range between perception threshold and 100% stimulation level |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (30 listed)
- Diagnosis of patients with CH shall be in accordance with The International Classification of Headache Disorders, 2nd Edition:
- At least 5 attacks fulfilling criteria B-D B. Severe or very severe unilateral orbital, supraorbital and/or temporal pain lasting 15-180 minutes if untreated
- Headache is accompanied by at least 1 of the following:
- ipsilateral conjunctival injection and/or lacrimation
- ipsilateral nasal congestion and/or rhinorrhoea
Key exclusion criteria (11 listed)
- Other significant neurological or disabling diseases which in the opinion of the clinician may interfere with the study
- Pregnancy or the wish to become pregnant during the study period
- Cardiac pacemaker and other neuromodulatory devices
- Psychiatric or cognitive disorders and/or behavioural problems which in the opinion of the clinician may interfere with the study
- Taking CH prophylactic medication for conditions other than CH which in the opinion of the clinician may interfere with the study
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 |
|---|---|---|
| occipital nerve stimulationAlso: Versitrel™, Pisces Quad® Plus, Versitrel™ Patient ProgrammerLow occipital bilateral Quad Plus, midline to laterally directed, secured by titan anchors, connected to Versitrel. No trial stimulation. Suggested stimulation parameters: Pulse width: 450, Amplitude: protocol, Rate: 60 | Device | 100% occipital nerve stimulation, 30% occipital nerve stimulation |
Primary outcome
The mean attack frequency (MAF) over the last 4 weeks in the 100% and the 30% treatment groups
Time frame: 6 months
An attack is defined as any attack recognised by the patient as being a CH attack. So also the attacks treated with oxygen or triptans.
11 secondary outcomes
The MAF during follow up
Time frame: for each 4 week period of the whole follow-up period
The mean attack intensity (on a scale from 0-10) will be calculated and will be compared between and within the 2 groups.
Time frame: over the last 4 weeks for each group at baseline, 6 and 12 months follow up
Rate of responders (>50% reduction in attack frequency in the last 4 weeks compared to baseline) will be calculated and compared between groups
Time frame: 6 and 12 months follow up
Economic evaluation
Time frame: baseline and 6 months follow-up
Anticipated group randomisation
Time frame: at 12 months follow-up
Awareness of paraesthesias
Time frame: weekly during 6 months follow up
The use of acute attack medication
Time frame: during the last 4 weeks at baseline periode and 6 months follow up
Patient satisfaction
Time frame: 6 and 12 months follow up
Responder identification
Time frame: 12 months follow up
Adverse events
Time frame: 1 year
MAF
Time frame: 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Feb 2020.
- Background: PubMed 19171831Burns B, Watkins L, Goadsby PJ. Treatment of intractable chronic cluster headache by occipital nerve stimulation in 14 patients. Neurology. 2009 Jan 27;72(4):341-5. doi: 10.1212/01.wnl.0000341279.17344.c9.
- Background: PubMed 17398309Burns B, Watkins L, Goadsby PJ. Treatment of medically intractable cluster headache by occipital nerve stimulation: long-term follow-up of eight patients. Lancet. 2007 Mar 31;369(9567):1099-106. doi: 10.1016/S0140-6736(07)60328-6.
- Background: PubMed 17362835Magis D, Allena M, Bolla M, De Pasqua V, Remacle JM, Schoenen J. Occipital nerve stimulation for drug-resistant chronic cluster headache: a prospective pilot study. Lancet Neurol. 2007 Apr;6(4):314-21. doi: 10.1016/S1474-4422(07)70058-3.
- Derived from this study: PubMed 36739508Brandt RB, Mulleners W, Wilbrink LA, Brandt P, van Zwet EW, Huygen FJ, Ferrari MD, Fronczek R; ICON study group. Intra- and interindividual attack frequency variability of chronic cluster headache. Cephalalgia. 2023 Feb;43(2):3331024221139239. doi: 10.1177/03331024221139239.
- Derived from this study: PubMed 34146510Wilbrink LA, de Coo IF, Doesborg PGG, Mulleners WM, Teernstra OPM, Bartels EC, Burger K, Wille F, van Dongen RTM, Kurt E, Spincemaille GH, Haan J, van Zwet EW, Huygen FJPM, Ferrari MD; ICON study group. Safety and efficacy of occipital nerve stimulation for attack prevention in medically intractable chronic cluster headache (ICON): a randomised, double-blind, multicentre, phase 3, electrical dose-controlled trial. Lancet Neurol. 2021 Jul;20(7):515-525. doi: 10.1016/S1474-4422(21)00101-0.
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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. This study is not recruiting at the moment.
Michel Ferrari, MD PhD principal investigator
Leiden University Medical Center
7 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing occipital nerve stimulation in people with Chronic Cluster Headache, run by Leiden University Medical Center at 7 sites in 4 countries.
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 30 inclusion and 11 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: finished, as of the sponsor's last update on 28 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in Netherlands, Belgium, Germany, Hungary. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The mean attack frequency (MAF) over the last 4 weeks in the 100% and the 30% treatment groups (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01151631, which also lists 5 linked publications.
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 28 Feb 2020.