Occipital Nerve Stimulation in Medically Intractable Chronic Cluster Headache (ICON)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified February 2011 by Leiden University Medical Center.
Recruitment status was  Recruiting
Sponsor:
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
Information provided by:
Leiden University Medical Center
ClinicalTrials.gov Identifier:
NCT01151631
First received: June 24, 2010
Last updated: July 11, 2011
Last verified: February 2011
  Purpose

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.


Condition Intervention Phase
Chronic Cluster Headache
Device: occipital nerve stimulation
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Occipital Nerve Stimulation in Medically Intractable Chronic Cluster Headache

Resource links provided by NLM:


Further study details as provided by Leiden University Medical Center:

Primary Outcome Measures:
  • The mean attack frequency (MAF) over the last 4 weeks in the 100% and the 30% treatment groups [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • The MAF [ Time Frame: for each 4 week period of the whole follow-up period ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Economic evaluation [ Time Frame: baseline and 6 months follow-up ] [ Designated as safety issue: No ]
  • Anticipated group randomisation [ Time Frame: at 12 months follow-up ] [ Designated as safety issue: No ]
  • Awareness of paraesthesias [ Time Frame: weekly during 6 months follow up ] [ Designated as safety issue: No ]
  • The use of acute attack medication [ Time Frame: during the last 4 weeks at baseline periode and 6 months follow up ] [ Designated as safety issue: No ]
  • Patient satisfaction [ Time Frame: 6 and 12 months follow up ] [ Designated as safety issue: No ]
    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.

  • Responder identification [ Time Frame: 12 months follow up ] [ Designated as safety issue: No ]
    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.

  • Adverse events [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    All and treatment-related adverse events will be documented by the investigators.


Estimated Enrollment: 144
Study Start Date: October 2010
Estimated Study Completion Date: January 2014
Estimated Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 100% occipital nerve stimulation
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.
Device: occipital nerve stimulation
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
Other Name: Versitrel™, Pisces Quad® Plus, Versitrel™ Patient Programmer
Sham Comparator: 30% occipital nerve stimulation
30% stimulation means a stimulation level at 30% of the range between perception threshold and 100% stimulation level
Device: occipital nerve stimulation
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
Other Name: Versitrel™, Pisces Quad® Plus, Versitrel™ Patient Programmer

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

* Diagnosis of patients with CH shall be in accordance with The International Classification of Headache Disorders, 2nd Edition:

A. 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

C. Headache is accompanied by at least 1 of the following:

  1. ipsilateral conjunctival injection and/or lacrimation
  2. ipsilateral nasal congestion and/or rhinorrhoea
  3. ipsilateral eyelid oedema
  4. ipsilateral forehead and facial sweating
  5. ipsilateral miosis and/or ptosis
  6. 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)

  1. Verapamil
  2. Lithium
  3. Methysergide
  4. Topiramate
  5. Gabapentin

Exclusion Criteria:

  • 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
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01151631

Contacts
Contact: Poldi Wilbrink, MD 0031715265042 l.a.wilbrink@lumc.nl
Contact: Onno Teernstra, MD PhD 0031455766652 oteernstra@gmail.com

Locations
Netherlands
Atrium medical centre Not yet recruiting
Heerlen, Netherlands, 6417
Contact: Onno Teernstra, MD PhD    0031455766652    oteernstra@gmail.com   
Principal Investigator: Onno Teernstra, MD PhD         
Leiden University Medical Center Recruiting
Leiden, Netherlands, 2333 ZA
Contact: Poldi Wilbrink, MD    0031715265042    l.a.wilbrink@lumc.nl   
Contact: Michel Ferrari, MD PhD    0031715262895    m.d.ferrari@lumc.nl   
Sub-Investigator: Poldi Wilbrink, MD         
Canisius Wilhelmina Hospital Recruiting
Nijmegen, Netherlands, 6532 SZ
Contact: Wim Mulleners, MD, PhD    003124 365 85 64    w.mulleners@cwz.nl   
Sponsors and Collaborators
Leiden University Medical Center
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
Investigators
Principal Investigator: Michel Ferrari, MD PhD Leiden University Medical Center
  More Information

Publications:
Responsible Party: Prof. Michel D. Ferrari, MD PhD, Department of Neurology, LUMC, Leiden, The Netherlands
ClinicalTrials.gov Identifier: NCT01151631     History of Changes
Other Study ID Numbers: ICON-01
Study First Received: June 24, 2010
Last Updated: July 11, 2011
Health Authority: Netherlands: Maastricht University Medical Centre

Additional relevant MeSH terms:
Headache
Cluster Headache
Trigeminal Autonomic Cephalalgias
Headache Disorders, Primary
Headache Disorders
Pain
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Brain Diseases
Central Nervous System Diseases

ClinicalTrials.gov processed this record on October 01, 2014