Constipation affects up to 20% of the US population, mainly women and the elderly. Affected individuals experience impaired quality of life and most are dissatisfied with current therapy. Our long-term goals are to develop therapies that remedy the underlying multifactorial dysfunction(s), and elucidate their neurobiologic and mechanistic bases. Through the previous application, we showed that biofeedback improved dyssynergic defecation and led to superior patient satisfaction. Here we aim to test new behavioral treatments for other dysfunctions and by integrating this with mechanistic studies we can reveal how the brain and the gut (gut- brain axis) interact, and how biofeedback modulates cortico-rectal function. We propose four specific aims: 1) Currently, biofeedback therapy requires a skilled therapist to train a patient using sophisticated equipment in a physiologic laboratory. We developed and tested a battery powered device for patients to use in their own home. We will determine if a community-based biofeedback therapy is as effective as laboratory- based biofeedback therapy. We will investigate and compare the efficacy, costs and outcomes of 100 patients with dyssynergic defecation, randomized to either home therapy or office-based therapy. 2) Our preliminary studies revealed that gut-brain function is deranged in dyssynergic patients, compared to controls and that biofeedback restores normal function. We will investigate the integrity of anorectal-brain interactions in 50 dyssynergic subjects (before and after biofeedback) and compare this with 25 healthy controls by measuring the cortical evoked potentials (CEP) after electrical stimulation of the anorectum (afferent) and the motor evoked potentials (MEP) following transcranial magnetic stimulation (efferent). 3) Currently, sensory conditioning of a hyposensitive rectum involves repetetive filling of a balloon with a hand-held syringe; this awkward approach reduces its effectiveness. We will test, in a randomized study, if barostat (pressure-driven computerized system) training is superior to syringe-assisted sensory training, in 70 constipated subjects with rectal hyposensitivity. Also, we will examine the neuroenteric mechanism(s) of rectal hyposensitivity by investigating anorectal sensori-motor function as well as CEPs and MEPs, before and after sensory training, and elucidate the locus (central versus peripheral) for neuronal modulation. 4) Constipation accompanied by abdominal pain is commonly associated with rectal hypersensitivity, a condition with no effective therapy. We developed and tested a new behavioral therapy, comprising of sensory adaptation training (SAT) using a barostat. In a RCT, we will compare SAT with escitalopram, a SSRI, in 60 constipated IBS patients and test its efficacy in reducing pain and improving hypersensitivity. These studies aim to define the mechanisms of, and evaluate new therapies for dyssynergia, rectal hyposensitivity and rectal hypersensitivity, and could significantly impact constipation treatments.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
7R01DK057100-11
Application #
8384363
Study Section
Clinical and Integrative Gastrointestinal Pathobiology Study Section (CIGP)
Program Officer
Hamilton, Frank A
Project Start
1999-10-01
Project End
2014-06-30
Budget Start
2012-02-17
Budget End
2014-06-30
Support Year
11
Fiscal Year
2011
Total Cost
$278,521
Indirect Cost
Name
Georgia Regents University
Department
Type
Schools of Medicine
DUNS #
966668691
City
Augusta
State
GA
Country
United States
Zip Code
30912
Erdogan, A; Rao, S S C; Thiruvaiyaru, D et al. (2016) Randomised clinical trial: mixed soluble/insoluble fibre vs. psyllium for chronic constipation. Aliment Pharmacol Ther 44:35-44
Rao, S S C; Benninga, M A; Bharucha, A E et al. (2015) ANMS-ESNM position paper and consensus guidelines on biofeedback therapy for anorectal disorders. Neurogastroenterol Motil 27:594-609
Coss-Adame, Enrique; Rao, Satish S C; Valestin, Jessica et al. (2015) Accuracy and Reproducibility of High-definition Anorectal Manometry and Pressure Topography Analyses in Healthy Subjects. Clin Gastroenterol Hepatol 13:1143-50.e1
Rao, Satish S C; Coss-Adame, Enrique; Tantiphlachiva, Kasaya et al. (2014) Translumbar and transsacral magnetic neurostimulation for the assessment of neuropathy in fecal incontinence. Dis Colon Rectum 57:645-52
Coss-Adame, Enrique; Rao, Satish S C (2014) Brain and gut interactions in irritable bowel syndrome: new paradigms and new understandings. Curr Gastroenterol Rep 16:379
Yu, Siegfried W B; Rao, Satish S C (2014) Anorectal physiology and pathophysiology in the elderly. Clin Geriatr Med 30:95-106
Fedewa, Amy; Rao, Satish S C (2014) Dietary fructose intolerance, fructan intolerance and FODMAPs. Curr Gastroenterol Rep 16:370
Bharucha, Adil E; Rao, Satish S C (2014) An update on anorectal disorders for gastroenterologists. Gastroenterology 146:37-45.e2
Coss-Adame, Enrique; Erdogan, Askin; Rao, Satish S C (2014) Treatment of esophageal (noncardiac) chest pain: an expert review. Clin Gastroenterol Hepatol 12:1224-45
Singh, S; Heady, S; Coss-Adame, E et al. (2013) Clinical utility of colonic manometry in slow transit constipation. Neurogastroenterol Motil 25:487-95

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