Idiopathic Chronic PancreatitisNCT00250484
TMS Treatment for Pain in Chronic Pancreatitis
A study testing Transcranial Magnetic Stimulation in people with Idiopathic Chronic Pancreatitis and Pain, run by Beth Israel Deaconess Medical Center at 1 site in United States.
Trial summary
The researchers aim to study the effects of repetitive transcranial magnetic stimulation (rTMS) on chronic visceral pain in patients with idiopathic chronic pancreatitis. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Idiopathic Chronic Pancreatitis, Pain
- What is being tested?
- Transcranial Magnetic Stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 23 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2004to Dec 2010
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
About this study
Official title: The Effect of 10-Day Treatment of Repetitive Transcranial Magnetic Stimulation on Abdominal Pain in Patients With Chronic Pancreatitis
The researchers aim to study the effects of repetitive transcranial magnetic stimulation (rTMS) on chronic visceral pain in patients with idiopathic chronic pancreatitis.
Read the 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.
- Conditions
- Idiopathic Chronic Pancreatitis, Pain
- Being tested
- Transcranial Magnetic Stimulation, Sham Transcranial Magnetic Stimulation
- Keywords
- analgesia, electric stimulation therapy, electric stimulation, pain, safety
- Medical subject headings
- Pain, Agnosia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transcranial Magnetic StimulationDevice
1Hz transcranial Magnetic Stimulation for 10 days for 26 minutes each day
Sham Transcranial Magnetic StimulationDevice
Sham procedure of transcranial Magnetic Stimulation for 10 days for 26 minutes each day
| Study group | Role | What they receive |
|---|---|---|
| Transcranial Magnetic Stimulation | Active comparator | Active treatment with TMS for 10 days. Receives: Device: Transcranial Magnetic Stimulation |
| Sham Transcranial Magnetic Stimulation | Sham comparator | Patients will receive no active TMS/treatment. Receives: Device: Sham Transcranial Magnetic Stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 1 year
Secondary outcomes (2)
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.
Measured: Baseline and end of treatment at approximately 1 year
Medication Use (Medication Diary)
Data was not collected or recorded because this outcome measure was no longer considered useful or relevant in the study.
Measured: Baseline and end of treatment at approximately 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Nov 2005 (estimated)
- Study startNov 2004
- Primary completionDec 2010
- Study completionDec 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Idiopathic Chronic PancreatitisStudies of the same condition, open and under way.
- More trials run by Beth Israel Deaconess Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Beth Israel Deaconess Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Steven Freedman, Beth Israel Deaconess Medical Center
- Investigators
- Steven D Freedman, MD, PhD, Principal investigator, Beth Israel Deaconess Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00250484
- Sponsor's protocol ID
- 2005P-000259 DK71851
- Other IDs
- R03DK071851
- Status last verified
- Sep 2017
- First submitted
- 7 Nov 2005
- Last updated
- 11 Oct 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No: No plan in protocol to share individual data
Study at a glance
From the registry record, last updated by the sponsor on 11 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of 10-Day Treatment of Repetitive Transcranial Magnetic Stimulation on Abdominal Pain in Patients With Chronic Pancreatitis
- ClinicalTrials.gov ID
- NCT00250484
- Acronym / sponsor ID
- 2005P-000259 DK71851
- Conditions
- Idiopathic Chronic Pancreatitis, Pain
- Keywords
- analgesia, electric stimulation therapy, electric stimulation, pain, safety
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Beth Israel Deaconess Medical CenterUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- Nov 2004
- Primary completion
- Dec 2010 (actual)
- Study completion
- Dec 2010 (actual)
- First posted
- 8 Nov 2005 (estimated)
- Results
- Posted 21 Oct 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Transcranial Magnetic Stimulation | Active comparator | Device: Transcranial Magnetic StimulationActive treatment with TMS for 10 days. |
| Sham Transcranial Magnetic Stimulation | Sham comparator | Device: Sham Transcranial Magnetic StimulationPatients will receive no active TMS/treatment. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Transcranial Magnetic Stimulation1Hz transcranial Magnetic Stimulation for 10 days for 26 minutes each day | Device | Transcranial Magnetic Stimulation |
| Sham Transcranial Magnetic StimulationSham procedure of transcranial Magnetic Stimulation for 10 days for 26 minutes each day | Device | Sham Transcranial Magnetic Stimulation |
Primary outcome
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.
2 secondary outcomes
Cognitive Assessment - Neuropsychological Battery
Time frame: Baseline and end of treatment at approximately 1 year
Medication Use (Medication Diary)
Time frame: Baseline and end of treatment at approximately 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Oct 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No. No plan in protocol to share individual data
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Steven D Freedman, MD, PhD principal investigator
Beth Israel Deaconess Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Transcranial Magnetic Stimulation in people with Idiopathic Chronic Pancreatitis and Pain, run by Beth Israel Deaconess Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Oct 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pain (Visual Analog Scale, CGI, PGA) (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Oct 2017.