Validation of Surrogate Measures in Irritable Bowel Syndrome (IBS)

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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Irritable Bowel Syndrome Colonic Diseases Colonic Diseases, Functional Digestive System Diseases Gastrointestinal Diseases Intestinal Diseases

Age range

18 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

NUH, Singapore

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

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

Treatment and study plan

Escitalopram treatment

Drug

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 names: Lexapro

Quantitative Sensory Testing

Behavioral

Rectal Distention Stimulation

Primary outcomes

To correlate clinical measures of IBS activity with experimental measures of central sensitisation and endogenous pain modulation

Time frame: 3 years
- To correlate clinical measures of IBS activity with experimental measures of central sensitisation and endogenous pain modulation over the course of six months
- 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.

Sponsors and collaborators

Lead sponsor

National University Hospital, Singapore

Other

Collaborators

NMRC, Singapore

Registry information

Important dates

Study start: 2009
Primary completion: 2012
Study completion: 2012
First posted: Jun 9, 2008
Registry last updated: Jan 7, 2014

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.

Completed