Irritable bowel syndrome (IBS) is a chronic medical condition which affects 10-15% of the population in industrialized countries. IBS is associated with a profound impairment of patient's quality of life, significant loss of productivity, and $2 billion in direct health care costs in the US alone, mainly due to unsatisfactory treatment. Patient heterogeneity in terms of disease pathogenesis, symptom expression and psychological co-morbidities are among the factors implicated in the variation of therapeutic responses. Therefore, the need to develop biological markers that can distinguish patients likely to benefit most from specific forms of treatment, and as importantly, from a placebo treatment, is imperative. We have recently concluded a 6 week randomized clinical trial in IBS patients (n=262) to examine the effects of placebo and acupuncture treatments, compared to a natural history control group. Blood samples were collected at baseline and at 3 and 6 weeks of follow-up. The positive results of this trial and sample availability allow us to perform a secondary Omics analysis examining patient variability in response to treatment. Our primary hypothesis is that serum proteins participate directly or indirectly to the brain-gut interactions associated with clinical responses in IBS. Our second hypothesis is that patients who clinically respond to placebo or acupuncture treatment have distinct serum protein profiles from those who don't respond. A third hypothesis is that placebo or acupuncture treatment results in changes in the serum proteome. We will incorporate various high throughput experimental approaches, some of them targeted to specific biological pathways and others leading to unbiased discoveries, to pursue the goals of this study. The serum proteomics analysis will be complemented with an investigation of common polymorphisms in genes of interest that emerge. Findings stemmed from such studies could lead to improvement of inclusion/exclusion criteria in randomized clinical trials based on biological screens. In terms of personalized medicine, findings could result in methodologies to enhance medication responses, adjust the doses or select medications with fewer side effects.

Public Health Relevance

Self healing using mind-body mechanisms, including placebo effects, can have a major impact on health care, though the biological process is poorly defined and understood. In a previous NIH-funded clinical study of 262 patients with irritable bowel syndrome (IBS), a gastrointestinal disease that affects up to 15% of the US population, we showed that placebo treatment, augmented by a supportive patient-practitioner interaction, could dramatically improve clinical symptoms and overall quality of life in those patients. The same study also indicated that acupuncture has potential benefit for some patients. The current application is a secondary, follow- up analysis of blood samples collected during the initial study. We will use high throughput approaches (Omics) and bioinformatics to identify biological markers for the various mind-body effects of placebo and acupuncture treatments. Our second goal is to generate a biological signature which can be used to predict individuals who respond and those who do not to such non-pharmacological treatments. Our findings will improve the design of clinical trials and contribute to the practice of personalized medicine.

Agency
National Institute of Health (NIH)
Institute
National Center for Complementary & Alternative Medicine (NCCAM)
Type
Research Project (R01)
Project #
5R01AT004662-05
Application #
8459026
Study Section
Special Emphasis Panel (ZAT1-SM (12))
Program Officer
Pontzer, Carol H
Project Start
2009-05-01
Project End
2014-04-30
Budget Start
2013-05-01
Budget End
2014-04-30
Support Year
5
Fiscal Year
2013
Total Cost
$395,969
Indirect Cost
$83,750
Name
Beth Israel Deaconess Medical Center
Department
Type
DUNS #
071723621
City
Boston
State
MA
Country
United States
Zip Code
02215
Hall, Kathryn T; Jablonski, Kathleen A; Chen, Ling et al. (2016) Catechol-O-methyltransferase association with hemoglobin A1c. Metabolism 65:961-967
Hall, Kathryn T; Tolkin, Benjamin R; Chinn, Garrett M et al. (2015) Conscientiousness is modified by genetic variation in catechol-O-methyltransferase to reduce symptom complaints in IBS patients. Brain Behav 5:39-44
Hall, Kathryn T; Loscalzo, Joseph; Kaptchuk, Ted J (2015) Genetics and the placebo effect: the placebome. Trends Mol Med 21:285-94
Hall, Kathryn T; Nelson, Christopher P; Davis, Roger B et al. (2014) Polymorphisms in catechol-O-methyltransferase modify treatment effects of aspirin on risk of cardiovascular disease. Arterioscler Thromb Vasc Biol 34:2160-7
Jensen, K B; Petrovic, P; Kerr, C E et al. (2014) Sharing pain and relief: neural correlates of physicians during treatment of patients. Mol Psychiatry 19:392-8
Hall, Kathryn T; Kaptchuk, Ted J (2013) Genetic biomarkers of placebo response: what could it mean for future trial design? Clin Investig (Lond) 3:311-314
Raicek, Jacqueline E; Stone, Bradley H; Kaptchuk, Ted J (2012) Placebos in 19th century medicine: a quantitative analysis of the BMJ. BMJ 345:e8326
Hall, Kathryn T; Lembo, Anthony J; Kirsch, Irving et al. (2012) Catechol-O-methyltransferase val158met polymorphism predicts placebo effect in irritable bowel syndrome. PLoS One 7:e48135
Bishop, Felicity L; Jacobson, Eric E; Shaw, Jessica R et al. (2012) Scientific tools, fake treatments, or triggers for psychological healing: how clinical trial participants conceptualise placebos. Soc Sci Med 74:767-74
Bishop, Felicity L; Adams, Alison E M; Kaptchuk, Ted J et al. (2012) Informed consent and placebo effects: a content analysis of information leaflets to identify what clinical trial participants are told about placebos. PLoS One 7:e39661

Showing the most recent 10 out of 15 publications