Validation of Surrogate Measures in Irritable Bowel Syndrome (IBS)

This study has been completed.
Sponsor:
Collaborator:
NMRC, Singapore
Information provided by (Responsible Party):
Medicine, National University Hospital, Singapore
ClinicalTrials.gov Identifier:
NCT00693732
First received: June 5, 2008
Last updated: January 6, 2014
Last verified: January 2014
  Purpose

Visceral and somatic hypersensitivity as evidence of central sensory sensitization occur in the majority of Irritable Bowel Syndrome (IBS) patients. We recently demonstrated abnormal endogenous pain modulation as a cause of the sensitization in IBS and identified the underlying dysfunctional neuromatrix using functional MR-imaging (fMRI). Endogenous pain mechanisms regulate, fine-tune and integrate sensory and homeostatic, including neuroendocrine, immune and autonomic nervous system processes. Specific measures of sensitization and endogenous pain modulation correlate with clinical measures of somatic and neuropathic pain, suggesting usefulness as surrogate markers for clinical pain outcomes. Validation of experimental measures as surrogate markers in IBS would provide a considerable advance in pathophysiological and therapeutic research in this pharmacoeconomically burdensome disease.


Condition Intervention Phase
Irritable Bowel Syndrome
Drug: Escitalopram treatment
Behavioral: Quantitative sensory testing
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Screening
Official Title: Validation of Surrogate Measures in Irritable Bowel Syndrome (IBS)

Resource links provided by NLM:


Further study details as provided by National University Hospital, Singapore:

Primary Outcome Measures:
  • To correlate clinical measures of IBS activity with experimental measures of central sensitisation and endogenous pain modulation [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    1. To correlate clinical measures of IBS activity with experimental measures of central sensitisation and endogenous pain modulation over the course of six months
    2. To correlate changes in brain and brainstem activation patterns in a subgroup of 15 patients and 15 controls by functional MRI with clinical IBS activity, symptom and pain scores, experimental measures of central sensitisation and endogenous pain modulation over the course of six months.


Enrollment: 30
Study Start Date: February 2009
Study Completion Date: January 2012
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1, IBS patients Drug: Escitalopram treatment
On study inclusion at Visit 2, patients will be successively randomised using a computer generated randomisation list to either placebo or escitalopram (Lundbeck Export A/S, Singapore) 10mg given at bedtime in the first 2 weeks, followed by 20mg in the next 6 weeks. The treatments will be identical in appearance and will be administered in double-blind fashion. Treatment with any anticoagulants, antidiabetics, antimigraine drugs, antispasmodics, analgesics, psychoactive agents including antidepressants, Zelmac®, TCM or acupuncture for IBS and any drugs affecting nociception as judged by investigator are prohibited during the entire study.
Other Name: Lexapro
Behavioral: Quantitative sensory testing
Rectal Distention Stimulation
Experimental: 2,Healthy controls Drug: Escitalopram treatment
On study inclusion at Visit 2, patients will be successively randomised using a computer generated randomisation list to either placebo or escitalopram (Lundbeck Export A/S, Singapore) 10mg given at bedtime in the first 2 weeks, followed by 20mg in the next 6 weeks. The treatments will be identical in appearance and will be administered in double-blind fashion. Treatment with any anticoagulants, antidiabetics, antimigraine drugs, antispasmodics, analgesics, psychoactive agents including antidepressants, Zelmac®, TCM or acupuncture for IBS and any drugs affecting nociception as judged by investigator are prohibited during the entire study.
Other Name: Lexapro
Behavioral: Quantitative sensory testing
Rectal Distention Stimulation

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

IBS patients:

  • One hundred fifty male and female IBS patients (Rome III criteria), aged 18 to 70 years, recruited from primary and secondary care via advertisements and referral networks.
  • Minimum IBS symptom rating of 75 in IBS severity scoring system (IBS-SSS) in last two weeks.
  • IBS discomfort or pain must have been patient's most prominent symptom.
  • A minimum of 40 patients each IBS-constipated (IBS-C) and IBS-diarrhoeic (IBS-D) (Rome III) to be included.
  • Patients must have been off all IBS and analgesic medication and any drugs potentially influencing sensory function for at least two weeks before study start.

Healthy controls:

  • Fifteen healthy controls aged 18 to 70 years without any gastrointestinal pathology or history of significant abdominal pain, bowel disorders, bloating or discomfort during the last 3 months.

Exclusion Criteria:

Exclusion criteria for both IBS patients and healthy controls:

  • Organic gastrointestinal or other significant systemic disease, including cardiovascular, psychiatric, neurological and endocrine diseases, as judged by investigator
  • Chronic or acute pain, except related to other functional syndromes (functional dyspepsia, chronic pelvic pain, fibromyalgia, migrane)
  • Bowel resections (except appendectomy)
  • Multiple abdominal operations, excluding hysterectomy
  • History of brain disease or brain surgery
  • Ongoing treatment with any anticoagulants, antidiabetics, antimigraine drugs, antispasmodics, analgesics, psychoactive agents including antidepressants, Zelmac®, TCM or acupuncture for IBS and any drugs affecting nociception as judged by investigator within last 14 days
  • Treatment with any investigational drug during the preceding 30 days
  • Pregnancy or lactation.
  • Claustrophobia
  • Metal implants in body (fMRI exclusion criterion)
  • No written informed consent obtained from subject
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00693732

Locations
Singapore
National University Hospital
Singapore, Singapore, 119074
NUH
Singapore, Singapore, 117597
Sponsors and Collaborators
National University Hospital, Singapore
NMRC, Singapore
  More Information

No publications provided

Responsible Party: Medicine, National University Hospital, Singapore
ClinicalTrials.gov Identifier: NCT00693732     History of Changes
Other Study ID Numbers: D/06/264
Study First Received: June 5, 2008
Last Updated: January 6, 2014
Health Authority: Singapore: Domain Specific Review Boards

Additional relevant MeSH terms:
Irritable Bowel Syndrome
Colonic Diseases, Functional
Colonic Diseases
Intestinal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Dexetimide
Citalopram
Antiparkinson Agents
Anti-Dyskinesia Agents
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Parasympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Muscarinic Antagonists
Cholinergic Antagonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Serotonin Agents
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs

ClinicalTrials.gov processed this record on August 21, 2014