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TMS Treatment for Pain in Chronic Pancreatitis

Primary Purpose

Idiopathic Chronic Pancreatitis, Pain

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Transcranial Magnetic Stimulation
Sham Transcranial Magnetic Stimulation
Sponsored by
Beth Israel Deaconess Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Idiopathic Chronic Pancreatitis focused on measuring analgesia, electric stimulation therapy, electric stimulation, pain, safety

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Beth Israel Deaconess Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Sham Comparator

Arm Label

Transcranial Magnetic Stimulation

Sham Transcranial Magnetic Stimulation

Arm Description

Active treatment with TMS for 10 days.

Patients will receive no active TMS/treatment.

Outcomes

Primary Outcome Measures

Pain (Visual Analog Scale, CGI, PGA)
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.

Secondary Outcome Measures

Cognitive Assessment - Neuropsychological Battery
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)
Data was not collected or recorded because this outcome measure was no longer considered useful or relevant in the study.

Full Information

First Posted
November 7, 2005
Last Updated
September 11, 2017
Sponsor
Beth Israel Deaconess Medical Center
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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1. Study Identification

Unique Protocol Identification Number
NCT00250484
Brief Title
TMS Treatment for Pain in Chronic Pancreatitis
Official Title
The Effect of 10-Day Treatment of Repetitive Transcranial Magnetic Stimulation on Abdominal Pain in Patients With Chronic Pancreatitis
Study Type
Interventional

2. Study Status

Record Verification Date
September 2017
Overall Recruitment Status
Completed
Study Start Date
November 2004 (undefined)
Primary Completion Date
December 2010 (Actual)
Study Completion Date
December 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Beth Israel Deaconess Medical Center
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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: 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. 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. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Idiopathic Chronic Pancreatitis, Pain
Keywords
analgesia, electric stimulation therapy, electric stimulation, pain, safety

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare Provider
Allocation
Randomized
Enrollment
23 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Transcranial Magnetic Stimulation
Arm Type
Active Comparator
Arm Description
Active treatment with TMS for 10 days.
Arm Title
Sham Transcranial Magnetic Stimulation
Arm Type
Sham Comparator
Arm Description
Patients will receive no active TMS/treatment.
Intervention Type
Device
Intervention Name(s)
Transcranial Magnetic Stimulation
Intervention Description
1Hz transcranial Magnetic Stimulation for 10 days for 26 minutes each day
Intervention Type
Device
Intervention Name(s)
Sham Transcranial Magnetic Stimulation
Intervention Description
Sham procedure of transcranial Magnetic Stimulation for 10 days for 26 minutes each day
Primary Outcome Measure Information:
Title
Pain (Visual Analog Scale, CGI, PGA)
Description
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.
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Cognitive Assessment - Neuropsychological Battery
Description
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.
Time Frame
Baseline and end of treatment at approximately 1 year
Title
Medication Use (Medication Diary)
Description
Data was not collected or recorded because this outcome measure was no longer considered useful or relevant in the study.
Time Frame
Baseline and end of treatment at approximately 1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility 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 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Steven D Freedman, MD, PhD
Organizational Affiliation
Beth Israel Deaconess Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
No plan in protocol to share individual data

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TMS Treatment for Pain in Chronic Pancreatitis

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