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TMS Treatment for Pain in Chronic Pancreatitis

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ClinicalTrials.gov Identifier: NCT00250484
Recruitment Status : Completed
First Posted : November 8, 2005
Results First Posted : October 21, 2016
Last Update Posted : October 11, 2017
Sponsor:
Collaborator:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
Steven Freedman, Beth Israel Deaconess Medical Center

Tracking Information
First Submitted Date  ICMJE November 7, 2005
First Posted Date  ICMJE November 8, 2005
Results First Submitted Date  ICMJE July 20, 2015
Results First Posted Date  ICMJE October 21, 2016
Last Update Posted Date October 11, 2017
Study Start Date  ICMJE November 2004
Actual Primary Completion Date December 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 30, 2016)
Pain (Visual Analog Scale, CGI, PGA) [ Time Frame: 1 year ]
Pain intensity and therefore changes in pain intensity were assessed using a 0-10 Visual Analog Scale where 0 represents the least amount of pain and 10 is the most pain imaginable. The pain evaluation was carried out by a blinded rater based off 1) baseline evaluation: 3 week long pain logs and a diary of pain medication intake, 2) treatment evaluations: participants were also asked to fill out daily pain logs following each TMS session and to keep a diary of pain medications during the CRC stay for the TMS course and 3)follow-up evaluation: finally, there was a follow up measurement 3 weeks after treatment.
Original Primary Outcome Measures  ICMJE
 (submitted: November 7, 2005)
  • Pain (Visual Analog Scale, CGI, PGA)
  • Medication use (medication diary)
Change History Complete list of historical versions of study NCT00250484 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 11, 2017)
  • Cognitive Assessment - Neuropsychological Battery [ Time Frame: Baseline and end of treatment at approximately 1 year ]
    Beck Depression Inventory (BDI), and Visual Analog Scale (VAS) for anxiety were assessed in subjects both as a baseline score before treatment was initiated as and upon conclusion of treatment. BDI is a 0-63 scale increasing with depression severity. A score from 0-13 indicates minimal depression, 14-19 indicates mild depression, 20-28 indicates moderate depression, and 28-63 indicates severe depression. Higher values represent a worse outcome. VAS is a pain assessment ranging from 0-10 increasing with pain severity. High values represent a worse outcome.
  • Medication Use (Medication Diary) [ Time Frame: Baseline and end of treatment at approximately 1 year ]
    Data was not collected or recorded because this outcome measure was no longer considered useful or relevant in the study.
Original Secondary Outcome Measures  ICMJE
 (submitted: November 7, 2005)
Safety (cognitive assessment - neuropsychological battery)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE TMS Treatment for Pain in Chronic Pancreatitis
Official Title  ICMJE The Effect of 10-Day Treatment of Repetitive Transcranial Magnetic Stimulation on Abdominal Pain in Patients With Chronic Pancreatitis
Brief 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Primary Purpose: Treatment
Condition  ICMJE
  • Idiopathic Chronic Pancreatitis
  • Pain
Intervention  ICMJE
  • Device: Transcranial Magnetic Stimulation
    1Hz transcranial Magnetic Stimulation for 10 days for 26 minutes each day
  • Device: Sham Transcranial Magnetic Stimulation
    Sham procedure of transcranial Magnetic Stimulation for 10 days for 26 minutes each day
Study Arms  ICMJE
  • Active Comparator: Transcranial Magnetic Stimulation
    Active treatment with TMS for 10 days.
    Intervention: Device: Transcranial Magnetic Stimulation
  • Sham Comparator: Sham Transcranial Magnetic Stimulation
    Patients will receive no active TMS/treatment.
    Intervention: Device: Sham Transcranial Magnetic Stimulation
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 13, 2015)
23
Original Enrollment  ICMJE
 (submitted: November 7, 2005)
32
Actual Study Completion Date  ICMJE December 2010
Actual Primary Completion Date December 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 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.

Exclusion Criteria:

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.

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; 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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00250484
Other Study ID Numbers  ICMJE 2005P-000259 DK71851
R03DK071851 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Plan Description: No plan in protocol to share individual data
Responsible Party Steven Freedman, Beth Israel Deaconess Medical Center
Study Sponsor  ICMJE Beth Israel Deaconess Medical Center
Collaborators  ICMJE National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators  ICMJE
Principal Investigator: Steven D Freedman, MD, PhD Beth Israel Deaconess Medical Center
PRS Account Beth Israel Deaconess Medical Center
Verification Date September 2017

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