Occipital nerve stimulation in patients with medically intractable chronic cluster headache:
A PET 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 form 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. The
efficacy of ONS in MICCH will be evaluated in the ICON study (Intractable
chronic Cluster headache Occipital Nerve stimulation study, see protocol
10.016).

Here we propose a clinical PET study in patients included in the ICON study in
the Netherlands to unravel the mechanism of ONS in patients suffering MICCH.

The focus of this present study will be to better understand the mechanism of
ONS in MICCH. The primary objective of this study is to investigate the
putative differences in rCBF at 6 months follow-up compared to baseline between
responders of ONS and non responders of ONS. The secondary objective is to
explore the putative differences in rCBF between high (100%) stimulation and
low (30%) stimulation.

This study will be embedded in the international ICON study. As it is known
from the literature that ONS takes weeks to months to have the optimum effect,
we decided to scan at baseline (before randomisation and implantation of the
device and stimulation, but after the baseline period of 3 months) and after 6
months of stimulation (two different conditions of stimulation: 30% and 100%
stimulation as explained in the protocol NL30794058.10) in on condition. So
each patient will get 2 PET scans. Because we only want to investigate the
effect of the stimulation (not the headache) on the rCBF, patients have to be
pain free two hours before scanning.

PET scan

Known risks of placing the catheter for the PET scan can be a hematoma.
The total amount of radioactivity will be 0,7 milliSievert (mSv) per [15O]
H2Owater scan. This means a total amount of radioactivity of 1,4 mSv. The
total amount of radioactivity that everybody is exposed to in one year, because
of background radiation from the universe and environment, is 2-2,5 mSv. If
patients have been exposed to radiation recently, the researcher will check if
the total amount will not exceed 10 mSv, which is the total amount of radiation
accepted in The Netherlands in these circumstances.

Patients included in the Netherlands will have to travel twice to the Vrije
Universiteit Medisch Centrum (VUMC), Amsterdam, The Netherlands for a PET scan.
The first PET scan will be performed at the end of baseline period and after
the decision of the study neurologist that the patient is still eligible and
will be randomised. An MRI scan of the brain will also be performed during this
first visit. The second visit will be after 6 months of stimulation, just
before the end of the blinded period of the trial. The PET scan of this second
visit will be performed in on condition
Travel expenses will be reimbursed and patients will receive 125 euro per PET
scan.