Transcranial Magnetic Stimulation (TMS) for Pain in Chronic Pancreatitis or Functional Gastrointestinal Disorders

This study has been completed.
Information provided by (Responsible Party):
Steven Freedman, Beth Israel Deaconess Medical Center Identifier:
First received: August 11, 2005
Last updated: March 10, 2015
Last verified: March 2015

August 11, 2005
March 10, 2015
November 2004
December 2010   (final data collection date for primary outcome measure)
  • Pain (visual analog scale) [ Time Frame: 5 months ] [ Designated as safety issue: No ]
    Examine whether slow repetitive rTMS has an analgesic effect as measured by changes in the Visual Analog Scale
  • Analgesic use (medication diary) [ Time Frame: 5 months ] [ Designated as safety issue: No ]
  • Pain (visual analog scale)
  • Medication use (medication diary)
Complete list of historical versions of study NCT00130052 on Archive Site
Number of participants with adverse events. [ Time Frame: 5 months ] [ Designated as safety issue: No ]
Not Provided
Not Provided
Transcranial Magnetic Stimulation (TMS) for Pain in Chronic Pancreatitis or Functional Gastrointestinal Disorders
The Effect of 10-day Treatment of Repetitive Transcranial Magnetic Stimulation on Abdominal Pain in Patients With Chronic Pancreatitis or Functional Gastrointestinal Disorders

The researchers aim to study the effects of repetitive transcranial magnetic stimulation (rTMS) on chronic pain in patients with chronic pancreatitis and functional gastrointestinal disorders.

The purpose of this protocol is to investigate a possible novel treatment for intractable visceral pain in patients with chronic pancreatitis and functional gastrointestinal disorders. Pain is a major contributor to the poor quality of life in this patient population. 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, suggesting 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 noninvasively 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 or functional gastrointestinal disorders 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.
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
  • Pain
  • Pancreatitis
  • Functional Gastrointestinal Disorders
  • Procedure: Transcranial Magnetic Stimulation
  • Procedure: Sham Transcranial Magnetic Stimulation
  • Experimental: TMS
    Subject will undergo rapid Transcranial Magnetic Stimulation (rTMS) at 90% of maximum.
    Intervention: Procedure: Transcranial Magnetic Stimulation
  • Sham Comparator: TMS Sham
    Subject will undergo a sham version of the rapid Transcranial Magnetic Stimulation (rTMS) protocol.
    Intervention: Procedure: Sham Transcranial Magnetic Stimulation
Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
December 2010
December 2010   (final data collection date for primary outcome measure)

Inclusion Criteria:

Patients will be eligible if:

  • They are age 18 years or older
  • They have daily abdominal pain for at least three months attributed to their chronic pancreatitis or functional gastrointestinal disorder
  • Average pain scores (VAS) in the baseline period higher than 4.

The diagnosis of chronic pancreatitis will be based on the existence of chronic abdominal pain and at least one of the four following criteria:

  • Calcifications throughout the pancreas on plain abdominal radiograph.
  • Endoscopically derived pancreatogram showing ductal changes consistent with chronic pancreatitis.
  • Abnormal secretin pancreatic function test with a peak bicarbonate level of less than 70 mEq/L (normal being >80 mEq/L).
  • Tissue diagnosis of chronic pancreatitis from a surgical specimen.

Other causes of chronic pancreatitis will be excluded as follows:

  • Hereditary pancreatitis based on genetic mutations or a family history of pancreatitis;
  • Alcohol abuse (the criteria for "at risk" [heavy] drinking established by the National Institute on Alcohol Abuse and Alcoholism [NIAAA], which suggest that the person is at risk for adverse consequences, are greater than 14 drinks per week or 4 drinks per occasion for men, and greater than 7 drinks per week or 3 drinks per occasion for women);
  • Medications associated with the development of pancreatitis (e.g. valproic acid, metronidazole, tetracycline, sulfonamides, nitrofurantoin, azathioprine, pentamidine), trauma, metabolic causes including hyperlipidemia and hypercalcemia, and autoimmune pancreatitis.

Exclusion Criteria:

Participants will be excluded if there are known complications of chronic pancreatitis requiring interventions including pseudocysts or pancreatic duct obstruction or if there is the presence of cancer. In addition, in order to minimize the risk of TMS, the following exclusion criteria will be followed:

  • Patients with a clinical diagnosis of severe depression including suicidal ideation
  • Prior neurosurgical procedure
  • Past history of epilepsy or family history of epilepsy
  • Previous head injury
  • Metal located in the head, i.e. shrapnel, surgical clips, or fragments from welding or metal implants.
  • Signs of increased intracranial pressure
  • Stroke
  • Chronic treatment with epileptogenic medications
  • Abnormal neurological examination other than as signs of the condition studied in the present protocol
  • Implanted pacemaker
  • Medication pump
  • Vagal stimulator
  • Deep brain stimulator
  • Transcutaneous electrical stimulation (TENS) unit and ventriculo-peritoneal shunt
  • Pregnancy
  • Other chronic medical conditions and history of substance abuse
  • History of medical and surgical therapies for pain within 3 months
18 Years and older
Contact information is only displayed when the study is recruiting subjects
United States
Not Provided
Steven Freedman, Beth Israel Deaconess Medical Center
Beth Israel Deaconess Medical Center
Not Provided
Principal Investigator: Steven D Freedman, MD, PhD Beth Israel Deaconess Medical Center/ Harvard Medical School
Beth Israel Deaconess Medical Center
March 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP