Neuroimaging and Biomarkers in Chronic Visceral Pain

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01602575
Recruitment Status : Completed
First Posted : May 21, 2012
Last Update Posted : May 14, 2018
National Institutes of Health (NIH)
National Center for Complementary and Integrative Health (NCCIH)
Information provided by (Responsible Party):
Kirsten Tillisch, MD, University of California, Los Angeles

Brief Summary:
The purpose of this study is to use functional magnetic resonance imaging (fMRI) to evaluate brain resting state networks, responses to abdominal stimuli and the effect of MBSR Training on these measures. The goal of this study is to identify biomarkers of IBS and assess the responsiveness these biomarkers after MBSR Training. A biomarker, or biological marker, is in general a substance or measure used as an indicator of a biological state. It is a characteristic that is measured and evaluated as an indicator of normal biological processes, disease processes, or responses to a therapeutic intervention, in this case MBSR.

Condition or disease Intervention/treatment Phase
Irritable Bowel Syndrome Behavioral: Mindfulness based Stress Reduction Training (MBSR) Not Applicable

Detailed Description:

Irritable bowel syndrome (IBS) is the most common chronic visceral pain disorder ranking among the most common of all persistent pain disorders with prevalence rates of 8-12% of the population.3 Diagnostic criteria for IBS include persistent abdominal pain and/or discomfort associated with changes in bowel habit. In the majority of patients, symptoms of other co-morbid pain conditions, such as epigastric pain (functional dyspepsia), pelvic pain (IC/PBS) and musculoskeletal pain (FM) are reported. Estimates are that >50% of the U.S. workforce experiences some type of pain and 13% lose productive work time due to pain over a 2 week period, leading to over 60 billion dollars per year in lost productivity costs.4 There are no generally agreed upon biomarkers for IBS, and diagnoses are exclusively based on subjective symptom criteria. As with most of the persistent pain disorders, IBS patients and their providers have increasingly embraced a biopsychosocial model incorporating psychological and social factors along with physiologic factors, and this forms the basis for integrative treatment approaches. This multimodal approach often incorporates Mind-Body treatments, and there is a growing literature showing clinical efficacy in IBS for interventions incorporating such Mind-Body approaches as meditation, hypnosis, yoga and cognitive therapy.5 However, there is little understanding of the physiological mechanisms underlying mind-body therapies, and for this reason optimization of the treatments for specific individuals and populations is difficult.

In this project we aim to use neuroimaging based biomarkers of IBS to examine which of these physiological measures show changes specific to a mind-body treatment with previously documented efficacy, Mindfulness Based Stress Reduction Training or MBSR. MBSR was chosen as a target treatment for several reasons: Recent clinical trial data suggests there is efficacy in improving IBS symptoms with MBSR, it has demonstrated prior success with other chronic pain conditions and there is considerable literature on meditation associated brain changes.

The primary Objective is to validate optimal biomarker candidates by assessment of treatment responsiveness in IBS patients following Mindfulness Based Stress Reduction (MBSR). The secondary objectives are to determine the generality of optimal biomarkers from Aim 1 and 2 and look at factors such as sex, age, co-morbid pain or mood symptoms, and/or baseline disease severity as moderators of the performance of candidate biomarkers.

Also, exploratory analyses will be performed to assess the effect of an 8 week MBSR training on measures of disease cognition, quality of life and mood defined by pre and post test scores on the behavioral measures listed in the study methods.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 119 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Neuroimaging Biomarkers of Mind-Body Treatment Response in Chronic Visceral Pain
Study Start Date : January 2013
Actual Primary Completion Date : March 20, 2016
Actual Study Completion Date : March 20, 2018

Arm Intervention/treatment
Experimental: mindfulness treatment
Mindfulness based stress reduction is the intervention in this single arm trial
Behavioral: Mindfulness based Stress Reduction Training (MBSR)
8 (2 hr) classes weekly of MBSR and required homework of MBSR practice approximately 30 minutes per day.
Other Names:
  • Spastic colon
  • Irritable colon
  • MBSR
  • Mindfulness Meditation

Primary Outcome Measures :
  1. Validate Optimal Biomarker candidates [ Time Frame: After MBSR training (8 weeks). ]
    To validate optimal brain biomarker candidates by assessment of treatment responsiveness in IBS patients following and 8 week course in Mindfulness Based Stress Reduction (MBSR).

Secondary Outcome Measures :
  1. Specificity, generality and moderation of biomarker response to MBSR treatment. [ Time Frame: Post MBSR training at 3 month follow up. ]

    Specificity of biomarker response to MBSR measured by changes in selected biomarker candidates correlation w/improvement in mindfulness at end of treatment & 3-month f/u.

    Determine generality of optimal biomarkers via examination of factors such as sex, age, co-morbid pain,mood, and/or baseline disease severity, as moderators of biomarker performance.

    Moderation of biomarker performance by symptoms: Disease severity, duration, and comorbid symptoms.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Patients must meet the Rome III criteria for IBS and lack red flag symptoms, such as weight loss, bloody stool, and fever. In the setting of clinical uncertainty on the part of the examining gastroenterologist, laboratory testing or prior medical records may be requested.
  2. Upper gastrointestinal symptoms, ie. dyspepsia or heartburn, are acceptable as long as IBS is their most bothersome symptom complex.
  3. Subject cannot have completed structured training in MBSR or other mindfulness or meditation.
  4. Subject cannot be currently practicing MBSR.
  5. A minimal severity score of 75 on the IBS-SSS at screening will be required to ensure at least mild-moderate symptoms at baseline.
  6. Literate in English
  7. Ambulatory without a need for assistive devices.
  8. Able to participate in the sitting and mild yoga positions required for the MBSR course.
  9. Right handed due to importance of laterality in brain imaging analysis
  10. Not pregnant, nursing or postpartum.
  11. No metals in body, including ferrous metallic implants and tattoos
  12. No history of claustrophobia.
  13. Able to lay still on back for extended period of time ( about 90 minutes).
  14. if unable to participate in the MRI portion of the study you may be eligible to come to the MBSR classes at no cost if you agree to complete the classes, homework and on-line questionnaires.

Exclusion criteria:

  1. Planned major medical intervention in the next 6 months (e.g. surgery), or surgery in the past 6 months.
  2. Presence of a significant and ongoing medical problem that would interfere with participation in the study or testing the study hypotheses (e.g. major heart disease, neurological disorders, inflammatory bowel disease, etc).
  3. Presence of a major psychiatric diagnosis such as schizophrenia, Bipolar disorder, Post-traumatic Stress Disorder, or Obsessive Compulsive disorder. However, subjects with a history of DSMIV diagnosis of Anxiety or Depression, in whom symptoms are not active will be allowed but noted for post-hoc analysis.
  4. use of centrally acting medications that will interfere with the neuroimaging testing (e.g. narcotic medications). As in past studies we will allow subjects taking stable doses of antidepressant medications (TCAs, SSRIs, SNRIs) for at least six months prior to study to participate.
  5. Body Mass Index greater than 30.
  6. Current or past history of chronic pain syndrome other than IBS in the IBS group (pain >6 months at any location).
  7. History of gastrointestinal surgery other than uncomplicated appendectomy or cholecystectomy.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01602575

United States, California
Oppenheimer Center for Neurobiology of Stress
Los Angeles, California, United States, 90095
Sponsors and Collaborators
University of California, Los Angeles
National Institutes of Health (NIH)
National Center for Complementary and Integrative Health (NCCIH)
Principal Investigator: Kirsten Tillisch, MD University of California, Los Angeles

Responsible Party: Kirsten Tillisch, MD, Principal Investigator, University of California, Los Angeles Identifier: NCT01602575     History of Changes
Other Study ID Numbers: R01AT007137 ( U.S. NIH Grant/Contract )
R01AT007137 ( U.S. NIH Grant/Contract )
First Posted: May 21, 2012    Key Record Dates
Last Update Posted: May 14, 2018
Last Verified: May 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Neuroimaging data will be shared after initial analysis and publication at to members of the Pain repository

Keywords provided by Kirsten Tillisch, MD, University of California, Los Angeles:

Additional relevant MeSH terms:
Irritable Bowel Syndrome
Visceral Pain
Colonic Diseases, Functional
Colonic Diseases
Intestinal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Nociceptive Pain
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms