Validation of Surrogate Measures in Irritable Bowel Syndrome (IBS)

NCT ID: NCT00693732

Last Updated: 2014-01-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-02-28
• Study Completion Date: 2012-01-31

Brief Summary

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.

Conditions

Irritable Bowel Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SCREENING
• Blinding Strategy: QUADRUPLE

Study Groups

1, IBS patients

Group Type: ACTIVE_COMPARATOR

Escitalopram treatment

Intervention Type: 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.

Quantitative sensory testing

Intervention Type: BEHAVIORAL

Rectal Distention Stimulation

2,Healthy controls

Group Type: EXPERIMENTAL

Escitalopram treatment

Intervention Type: 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.

Quantitative sensory testing

Intervention Type: BEHAVIORAL

Rectal Distention Stimulation

Interventions

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.

Intervention Type: DRUG

Quantitative sensory testing

Rectal Distention Stimulation

Intervention Type: BEHAVIORAL

Other Intervention Names

Lexapro

Eligibility 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

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

NMRC, Singapore

UNKNOWN

Sponsor Role: collaborator

National University Hospital, Singapore

OTHER

Sponsor Role: lead

Responsible Party

Medicine

Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

NUH

Singapore, Singapore, Singapore

National University Hospital

Singapore, , Singapore

Countries

Singapore

Other Identifiers

D/06/264

Identifier Type: -

Identifier Source: org_study_id