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The Effect of a 10-day Course of Transcranial Magnetic Stimulation on Abdominal Pain in Patients With Locally Advanced and Advanced Pancreatic Cancer, a Randomized Phase II Study.


Phase 2
18 Years
65 Years
Open (Enrolling)
Both
Pain, Visceral Pain, Pancreatic Cancer

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Trial Information

The Effect of a 10-day Course of Transcranial Magnetic Stimulation on Abdominal Pain in Patients With Locally Advanced and Advanced Pancreatic Cancer, a Randomized Phase II Study.


The primary aim of this protocol is to investigate a possible novel treatment for visceral
pain in patients with locally advanced or advanced pancreatic cancer. Pain is a major
contributor to the poor quality of life in patients with pancreatic cancer. Most patients
with locally advanced or advanced pancreatic cancer have abdominal pain that requires
treatment with increasing doses of narcotic pain medication. The refractory nature of
pancreatic cancer pain to pharmacologic therapy led us to hypothesize that one mechanism
leading to pain in these patients is dysfunction of brain cortical regulation of visceral
sensation. This notion is supported by the finding that deep electrical stimulation of the
brain can produce pain relief in patients with intractable pain due to progressive cancers
of various types (Young and Brechner 1986). In addition, patients with pancreatitis, a
non-malignant pancreatic condition causing chronic pain, can continue to experience
disabling pain even after total pancreatectomy. These finding suggests that pain symptoms in
pancreatic cancer can be sustained by a pancreas-independent, neural-based mechanisms in the
brain.

Visceral sensation is processed in the secondary somatosensory area (SII). Therefore,
pancreatic cancer pain may be sustained by dysfunction of SII rather than by local effects
of the cancer alone. We hypothesize further, that dysfunction of SII is one of
hyper-excitability. According to this hypothesis, suppression of SII activity may help
control the pain in patients with pancreatic cancer and may provide synergy with
pharmacologic treatment.

Temporary inhibition of SII activity can be obtained by a novel, non-invasive procedure
called transcranial magnetic stimulation (TMS). TMS can suppress brain excitability beyond
the duration of the direct application of TMS if appropriate stimulation parameters are
utilized. This hypothesis is supported by a sham controlled, double blind pilot trial of 5
subjects with idiopathic chronic pancreatitis: active rTMS applied to SII resulted in
significant pain improvement in three of the subjects while sham did not provide any benefit
in any of these patients. Furthermore, recent evidence suggests that stimulation of other
brain areas, such as the dorsolateral pre-frontal cortex, can modulate acute, experimentally
invoked pain (Graff-Guerrero et al 2005).

We will rigorously test the hypothesis that pain due to pancreatic cancer is sustained by
dysfunction of SII characterized by hyperexcitability through two specific aims:

1. The first aim of this study is to examine whether 1Hz repetitive TMS (rTMS) applied to
SII for ten days during two consecutive weeks in patients with abdominal pain due to
pancreatic cancer has an analgesic effect.

1. The primary outcome for this aim is the difference in pain score level on the
Visual Analogue Scale at Day 11 and at Day 28 compared to the week before rTMS.
The null hypothesis is that there is no difference in pain score between pre and
post-treatment.

2. The secondary outcome for this aim is to assess the difference in the use of
narcotics for pain control on Day 11 and Day 28 compared to Day 1. The null
hypothesis is that there is no difference in narcotic use (in IV morphine
equivalency units) between pre and post-treatment.

2. The second aim of the study is to assess the safety of rTMS in patients with pancreatic
cancer.

3. The third aim of this study is to investigate whether rTMS treatment is associated with
a change in the activity of right SII using magnetic resonance spectroscopy. Therefore
we will compare the levels of these substances between the two different time points
(baseline and post-treatment) and between left and right SII. We expect a decrease in
the excitatory neurotransmitters levels (Glutamine - Glx) in the stimulated area as a
result of the inhibitory rTMS.

SAFETY In a pilot study of chronic pancreatitis patients, no subject experienced adverse
effects from a single session of rTMS. Subjects in an ongoing study of a 10-day course or
rTMS in chronic pancreatitis patients also have not experienced adverse events (10 patients
thus far). Fifteen-day courses of rTMS have been used for the treatment of various
neuropsychiatric diseases without any complications if safety guidelines are carefully
followed. We 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, we hypothesize that the proposed rTMS protocol will be
safe for our patient population.


Inclusion Criteria:



- Locally advanced or metastatic pancreatic cancer

- Abdominal pain attributable to pancreatic cancer that requires daily narcotic use

- Stable narcotic dosage the week before study entry

- A computed tomography of the abdomen within four weeks of study entry

- CA19-9 within four weeks of study entry

- ECOG Performance status >=3

Exclusion Criteria:

- Known brain metastasis

- Patients with major depression with suicidal risk

- Prior neurosurgical procedures

- History of epilepsy

- Previous head injury

- History of Stroke

- Abnormal neurological examination other than as signs of the condition studied in the
present protocol

- Contraindication to TMS:

Implanted pacemaker;Medication pump;Vagal stimulator;Deep brain stimulator;Metallic
hardware in the head or scalp: shrapnel, surgical clips, or fragments from welding;Signs
of increased intracranial pressure

- TENS unit and ventriculo-peritoneal shunt

- Pregnancy

Unable to undergo a brain MR

- claustrophobia refractory to anxiolytics

- ferromagnetic metal in the body such as a prosthetic heart valve, a pacemaker, or a
brain aneurysm clip).

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Pain (visual analog scale, CGI,PGA); Medication use (medication diary)

Outcome Time Frame:

1 year

Safety Issue:

Yes

Principal Investigator

Felipe Fregni, MD, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Beth Israel Deaconess Medical Center

Authority:

United States: Federal Government

Study ID:

2005P-000311

NCT ID:

NCT00324428

Start Date:

May 2006

Completion Date:

February 2008

Related Keywords:

  • Pain
  • Visceral Pain
  • Pancreatic Cancer
  • TMS
  • Visceral Pain
  • Analgesia
  • Pancreatic Cancer
  • Cancer
  • Electric stimulation therapy
  • Electric stimulation
  • Pain
  • Safety
  • Pancreatic Neoplasms

Name

Location

Beth Israel Deaconess Medical CenterBoston, Massachusetts  02215