TMS Treatment for Pain in Chronic Pancreatitis
Condition: Idiopathic Chronic Pancreatitis; Pain
MeSH terms: Pancreatitis; Pancreatitis, Chronic
Study type: Interventional

Summary: 
      The researchers aim to study the effects of repetitive transcranial magnetic stimulation
      (rTMS) on chronic visceral pain in patients with idiopathic chronic pancreatitis.
    

Detailed description: 
      The purpose of this protocol is to investigate a possible novel treatment for intractable
      visceral pain in patients with chronic pancreatitis. Pain is a major contributor to the poor
      quality of life in patients with chronic pancreatitis. The refractory nature of this
      condition to medical and surgical procedures prompted us to hypothesize that one mechanism
      leading to pain in these patients is the dysfunction of brain cortical regulation of visceral
      sensation. This notion is particularly supported by findings that patients with chronic
      pancreatitis can continue to experience disabling pain even after total pancreatectomy. This
      suggests that symptoms are sustained by a pancreas-independent, neural-based mechanism.
      Visceral sensation is particularly processed in the secondary somatosensory area - SII.
      Therefore, chronic pancreatitis pain may be sustained by a dysfunction of SII rather than by
      pancreatic inflammation alone. The researchers hypothesize further that the dysfunction of
      SII is one of hyper-excitability. According to this hypothesis, suppression of SII activity
      may help control the pain in patients with chronic pancreatitis. Temporary inhibition of SII
      activity can be obtained by a novel tool, namely transcranial magnetic stimulation (TMS),
      which can suppress brain excitability non-invasively beyond the duration of the TMS if
      appropriate stimulation parameters are employed. In the initial sham controlled, double blind
      pilot trial of 5 subjects with idiopathic chronic pancreatitis, TMS applied to SII resulted
      in significant pain improvement in 3 of the subjects. The researchers will rigorously test
      the hypothesis that chronic pancreatitis pain is sustained by a dysfunction of SII
      characterized by hyperexcitability through two specific aims:

        1. The first aim of this study is to examine whether slow repetitive TMS (rTMS) applied to
           SII in patients with pain and chronic pancreatitis has an analgesic effect as measured
           by changes in the Visual Analogue Scale (VAS) for pain and a decrease in analgesic
           intake, as well as an overall improvement in quality of life. In addition, if this study
           finds a significant effect of rTMS on pain reduction, the duration of this effect will
           be further assessed. TMS will be applied at parameters of stimulation known to decrease
           excitability.

        2. The second aim of the study is to assess the safety of rTMS in this patient population.
           In the pilot study none of the patients experienced any adverse effects of a single
           session of rTMS. However, the extension of the study protocol to a 10-day course of
           daily rTMS requires careful safety assessment. Fifteen-day courses of rTMS have been
           used for treatment of various neuropsychiatric diseases without any complications if
           safety guidelines are carefully followed. The researchers will adhere to the current
           safety recommendations for rTMS endorsed by the International Society for Transcranial
           Stimulation and the International Federation for Clinical Neurophysiology. Therefore,
           the researchers hypothesize that the proposed rTMS protocol will be safe for the patient
           population.

        3. The third aim of the study is to study the physiologic mechanism of action of rTMS in
           these patients using magnetic resonance imaging (MRI). In doing so, the researchers aim
           to contribute to a better understanding of the pathophysiology of chronic pain in
           patients with pancreatitis by investigating the correlation between pain improvement and
           areas of brain activation. This could lead to the development of markers of therapeutic
           response. Magnetic resonance spectroscopy allows a non-invasive measure of GABAergic and
           glutamatergic activity in a defined volume of interest in the brain. The researchers
           hypothesize that the balance of GABA and glutamate will be abnormal in SII in patients
           with pain from chronic pancreatitis, with a relative decrease in GABA and increase in
           glutamate indicating an abnormal, hyperexcitable dysfunction. This abnormality will be
           normalized by rTMS in correlation with its analgesic effect.
    

Intervention name(s): Transcranial Magnetic Stimulation; Sham Transcranial Magnetic Stimulation
Intervention type(s): Device; Device
Intervention description(s): 1Hz transcranial Magnetic Stimulation for 10 days for 26 minutes each day; Sham procedure of transcranial Magnetic Stimulation for 10 days for 26 minutes each day
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Primary purpose: Treatment
Keywords: analgesia; electric stimulation therapy; electric stimulation; pain; safety