Electrical Stimulation of the Sphenopalatine Ganglion for the Treatment of Migraine Headaches
This application proposes a clinical study of electrical stimulation of the sphenopalatine
ganglia (SPG) as a treatment for up to three individuals with episodic migraine headache.
The present study is aimed at obtaining pilot data to guide a future controlled trial of
this treatment modality. The study population will include individuals suffering from
episodic migraine headaches with chronic severe disability, as demonstrated by the Migraine
Disability Assessment Questionnaire (Lipton, 2000) and Headache Impact Test short form
(HIT-6™) (Kosinski, 2003).
The treatment involves implantation of an electrode into the SPG. The electrode is connected
subcutaneously to an infraclavicular stimulator (PrimeAdvanced™ 37702 Multi-program
Neurostimulator System, Medtronic Inc., Minneapolis MN). Proper electrode placement will be
verified using anatomic and physiologic techniques. Participants will receive the Medtronic
Model 3389 or 3387 lead, or Medtronic subcompact lead Model 3776-45, 3776-60, or 3776-75.
Stimulation will be delivered in a range of frequencies from 20 to 130 Hz, and pulse width
from 60 to 450 μsec, and a titrated voltage. The voltages used for chronic stimulation may
range up to the pulse generator maximum of 10.5 volts but are anticipated to generally be
below 3 volts, keeping below the 30 µcoulomb/cm² charge density safety limit, and below the
threshold for adverse stimulation-related effects. The minimum number of contacts on the
quadripolar leads will be activated as necessary to produce a response.
The Prime Advanced neurostimulator to be used in this study allows the clinician to set all
stimulation parameters including the maximum allowable amplitude. It is our responsibility
to assure that appropriate stimulation parameters are used to result in appropriate
electrical exposure charge density) below a 30 µC/cm2/phase limit. As is done with
commercially available neurostimulators, during this study, we will utilize the charts
presented in Figures 1 and 2 below to assist in selection of programming parameters, and
this programming will be maintained by software controls within the neurostimulator.
For this exploratory study of 3 patients, the maximum electrical stimulating parameters,
resulting electrical exposure (e.g., charge density), will be determined using the methods
described above. It is our responsibility to assure that safe stimulation parameters are
used at all times and that the maximum settings do not exceed the safety limits. Our plan
is to begin with lead 3776 if possible, because it does not require an extra extension, but
we would use 3387 or 3389 if clinically indicated.
The proposed study is a physician-sponsored research investigation of three patients, and
the attention to stimulation parameters will be much greater than can be expected for a
commercially released product. It is our responsibility within this investigational study
to insure the selected stimulation parameters do not exceed the safety limit of
30μC/cm2/phase. Patients participating in the study will only be able to lower stimulation
amplitudes, thereby keeping stimulation parameters BELOW any clinician set maximum. The
only programs available to or accessible by the patients will maintain the previously
described parameter set limitations. Thus, the programming of the Implantable Programmable
Generator (IPG) will keep the three patients from stimulating outside or above the set and
The primary outcome measures for assessing the efficacy of migraine treatment will be a
subject reported daily diary noting frequency and intensity of headaches. During this
investigation we will obtain preliminary controlled data on the safety and efficacy of SPG
stimulation for migraine treatment.
Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Migraine Relief at 2 hours post stimulation
Pain is rated at stimulation and 2 hours after stimulation initiated based on four point categorical scale, FDA-approved, where 0 = no headache pain, 1= mild pain, 2 = moderate pain, 3 = severe pain. This scale has been used since 1991 for all regulatory submission migraine protocols. Each migraine is categorized in a binary fashion as meeting the endpoint at 2 hours. Migraine relief or Pain relief is defined as moving from pain levels of 3 to 2 down to 1 or 0.
Stewart J Tepper, MD
The Cleveland Clinic
United States: Food and Drug Administration
IDE Number : G100007
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