SAT vs Escitalopram for Rectal Hypersensitivity

Randomized Controlled Trial of Treating Rectal Hypersensitivity - Comparing Escitalopram With Sensory Adaptation Training

Constipation is a common digestive disorder. After excluding dietary factors, drugs and other secondary causes, at least three broad pathophysiologic subtypes are recognized- dyssynergic defecation, constipation-predominant irritable bowel syndrome (IBS-C) and slow transit constipation (STC), all predominantly affect women and elderly. Many patients also demonstrate abnormal rectal perception with both rectal hyposensitivity and hypersensitivity being common. Recent surveys show that most constipated patients are dissatisfied with current therapy. Also, constipated patients showed significant psychological dysfunction and impaired quality of life. OBJECTIVE: To investigate a novel biofeedback technique of improving rectal hypersensitivity.

METHODS: A large compliant balloon attached to a barostat was placed in the rectum in 8 patients with rectal hypersensitivity (urgency/pain threshold <30 mm Hg). Sensory deconditioning was performed by incremental balloon distensions (1-2 mmHg) until normal thresholds were reached.

Study Overview

• Status: Completed
• Conditions: Rectal Hypersensitivity; Irritable Bowel Syndrome-Constipation
• Intervention / Treatment: Procedure: Sensory Adaptation Training; Drug: Escitalopram Therapy

Detailed Description

To investigate a novel biofeedback technique of improving rectal hypersensitivity using rectal barostat and to compare this with clinical standard of care comprising of low dose antidepressant therapy with escitalopram. Patients will be randomized to sensory adaptation training or escitalopram in a 1:1 ratio

• Study Type: Interventional
• Enrollment (Actual): 55
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Augusta University
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals and Clinics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

All patients must fulfill the diagnostic criteria for IBS-C (Rome III) as defined below and have rectal hypersensitivity (see below).

• Patients must report recurrent abdominal pain or discomfort for at least 3 days per month in the last 3 months with two or more of the following symptoms:

  • Improvement with defecation; and/or
  • Onset associated with a change in frequency of stool; and/or
  • Onset associated with a change in form (appearance) of stool
• No structural diseases

• On a diary:

  • Pain/discomfort for at least 2 days/week;
  • No loose or watery stool <25% of bowel movements.

Exclusion Criteria:

• Patients with mixed-IBS.
• Patients currently on SSRI or MAO inhibitors. Patients on stable doses of other antidepressants will be included provided the dose is unchanged during study.
• Patients taking drugs that are constipating, (e.g.; calcium channel antagonists will either be excluded or drug discontinued)
• Patients with co-morbid illnesses; severe cardiac disease, chronic renal failure or previous gastrointestinal surgery except cholecystectomy and appendectomy.
• Neurologic diseases e.g.; head injury, epilepsy, multiple sclerosis, strokes, spinal cord injuries.
• Impaired cognizance (mini mental score of < 15) and/or legally blind.
• Pregnant or likely to conceive during the course of the study. Women with potential for pregnancy must be willing to use contraceptive measures during the study. Urinary pregnancy tests will be performed on such women prior to any radiologic procedures.
• Hirschsprung's disease.
• Alternating constipation and diarrhea (22).
• Ulcerative/Crohns colitis.
• Previous pelvic surgery, rectocele/bladder repair, radical hysterectomy, anal surgery.
• Rectal prolapse or anal fissure.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Sensory Adaptation training; a large compliant balloon is placed in the rectum attached to a barostat. The balloon is distended in 1 mm increments until patient reports moderate discomfort and then increased in 1 mm increments until maximum tolerable pressure. Gradually over 6 training sessions, administered biweekly, the maximum tolerable pressure is increased over 3 months, if treatment is successful.	Procedure: Sensory Adaptation Training; This study will last for approximately 3 months and will include 4-6 clinic visits with each visit lasting 2 hours every week or every 2 weeks. At the beginning of each visit we will ask you about your health status and level of satisfaction of your bowel habits. We will then place the pencil-thick probe and balloon inside your rectum and attach it to the barostat device and a computer. We will increase and decrease the volumes of the balloon until the most pressure you can tolerate or a certain level of pressure as measured by the machine is reached, whichever occurs first. You will continue to keep stool diaries and pain diaries for 7 days before and after each visit.; Other Names: Barostat procedure
Experimental: Escitalopram Therapy; Patients randomized to this arm will receive daily 10 mg escitalopram for 3 months. If the medication is effective their bowel symptoms and pain thersholds will improve.	Drug: Escitalopram Therapy; Escitalopram; 10 mg every day, orally.; Other Names: Lexapro (Escitalopram) therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rectal Sensory Thresholds	The primary physiologic outcome measure is increase in rectal sensory thresholds after treatment. A rectal hypersensitivity responder is defined as an individual who show at least 20% increase in two or more sensory thresholds (first, desire and urge defecate/pain) after treatment when compared to baseline, and will be compared between the SAT and escitalopram groups. An overall responder is defined as both a hypersensitivity responder and abdominal pain responder.	Trial entry and at the end of 3 months
Abdominal Pain	The symptomatic outcome measure is decrease in pain score as assessed by daily pain logs where pain is scored on a scale of 0 to 4, after treatment when compared to the baseline period. A pain responder is defined as a subject with 30% decrease in pain compared to baseline.	Trial entry and at the end of 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Global Bowel Satisfaction Score (GSA)	The global bowel satisfaction will be analysed using a visual analog scale 0-10 cm (0 - very dissatisfied, 10 - completely satisfied).	Trial entry and at the end of 3 months
Bowel symptoms	We will assess the number of complete spontaneous bowel movements, mean straining scores, mean stool consistency (Bristol Stool Scale) (numerical mean scores for individual questions) between the two groups.	Trial entry and at the end of 3 months
Rectal compliance	We will assess the changes in intrarectal pressures and intrarectal volumes during Barostat rectal balloon distention between the two groups.	Trial entry and at the end of 3 months
IBS quality of life	The IBS quality of life will be assessed using the 8 domains of IBS-QOL and compared between the two groups.	Trial entry and at the end of 3 months
Psychological profiles	The psychological profiles will be assessed using the SCL-90R questionnaire and compared between the two groups.	Trial entry and at the end of 3 months

Collaborators and Investigators

• Sponsor: Augusta University
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Principal Investigator: Satish SC Rao, MD, PhD, Augusta University

Publications and helpful links

General Publications

• Rao SSC, Coss-Adame E, Yan Y, Erdogan A, Valestin J, Ayyala DN. Sensory Adaptation Training or Escitalopram for IBS With Constipation and Rectal Hypersensitivity: A Randomized Controlled Trial. Clin Transl Gastroenterol. 2021 Jul 13;12(7):e00381. doi: 10.14309/ctg.0000000000000381.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2007
• Primary Completion (Actual): December 31, 2015
• Study Completion (Actual): December 31, 2019

Study Registration Dates

• First Submitted: December 21, 2007
• First Submitted That Met QC Criteria: December 31, 2007
• First Posted (Estimate): January 2, 2008

Study Record Updates

• Last Update Posted (Actual): August 6, 2020
• Last Update Submitted That Met QC Criteria: August 4, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Immune System Diseases; Signs and Symptoms, Digestive; Gastrointestinal Diseases; Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Hypersensitivity; Irritable Bowel Syndrome; Constipation; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Antidepressive Agents, Second-Generation; Antiparkinson Agents; Anti-Dyskinesia Agents; Citalopram; Dexetimide
• Other Study ID Numbers: 2R01 KD57100-05A2; 2R01DK057100-06A2 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No