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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified August 2009 by Beth Israel Deaconess Medical Center.
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by:
Beth Israel Deaconess Medical Center
ClinicalTrials.gov Identifier:
NCT00130052
First received: August 11, 2005
Last updated: August 28, 2009
Last verified: August 2009
  Purpose

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.


Condition Intervention Phase
Pain
Pancreatitis
Functional Gastrointestinal Disorders
Procedure: Transcranial Magnetic Stimulation
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: The Effect of 10-day Treatment of Repetitive Transcranial Magnetic Stimulation on Abdominal Pain in Patients With Chronic Pancreatitis or Functional Gastrointestinal Disorders

Resource links provided by NLM:


Further study details as provided by Beth Israel Deaconess Medical Center:

Primary Outcome Measures:
  • Pain (visual analog scale)
  • Medication use (medication diary)

Secondary Outcome Measures:
  • Safety

Estimated Enrollment: 32
Study Start Date: November 2004
Detailed Description:

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.
  Eligibility

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

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
  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: NCT00130052

Locations
United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
Sponsors and Collaborators
Beth Israel Deaconess Medical Center
Investigators
Principal Investigator: Steven D Freedman, MD, PhD Beth Israel Deaconess Medical Center/ Harvard Medical School
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00130052     History of Changes
Other Study ID Numbers: 2004P-000352
Study First Received: August 11, 2005
Last Updated: August 28, 2009
Health Authority: United States: Institutional Review Board

Keywords provided by Beth Israel Deaconess Medical Center:
analgesia
electric stimulation therapy
electric stimulation
pain
safety

Additional relevant MeSH terms:
Digestive System Diseases
Gastrointestinal Diseases
Pancreatitis
Pancreatitis, Chronic
Pancreatic Diseases

ClinicalTrials.gov processed this record on July 29, 2014