Study of Endogenous Inhibitory Modulation During Gastric and Somatic Stimulation

Activation of Endogenous Inhibitory Modulation During Gastric and Somatic Stimulation in Functional Dyspepsia Patients and Healthy Controls

Visceral hypersensitivity as evidence of central sensory sensitization is evident in many patients with functional disorders such as functional dyspepsia (FD) and irritable bowel syndrome (IBS). We recently demonstrated both somatic hypersensitivity and abnormal endogenous pain modulation in IBS, both of which indicate central sensitization as a crucial mechanism in IBS. Endogenous pain mechanisms regulate, fine-tune and integrate sensory and homeostatic, including neuroendocrine, immune, motor and autonomic nervous system processes. Hitherto, no studies have investigated the role endogenous pain modulation in FD. Abnormal modulation could explain several of the symptom complexes associated with FD and provide a rationale for exploration of new treatments.

The current study was designed to

1. investigate the gastric sensitivity in FD patients and healthy controls during gastric capsaicin stimulation
2. assess the endogenous pain inhibitory modulation system in FD patients and healthy controls during heterotopic stimulation

Study Overview

• Status: Completed
• Conditions: Functional Dyspepsia
• Intervention / Treatment: Procedure: gastric capsaicin with heterotopic stimulation/ distraction

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Singapore
  • Singapore, Singapore, 119074
    • National University Hospital
  • Singapore, Singapore, 119742
    • National University of Singapore

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

FD patients:

• Eighty male and female FD patients according to Rome III criteria (Drossman, 2006), aged 18 to 70 years, will be recruited from primary and secondary care via advertisements and our referral networks.
• FD discomfort or pain should be the most prominent symptom.
• Patients must have been off all FD and analgesic medication and any drugs potentially influencing sensory function for at least two weeks before study start and be able to remain off such medication for the duration of the study period.

Healthy controls:

• Forty male and female healthy volunteers, 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 will be recruited.

Exclusion Criteria:

Exclusion criteria for both FD patients and healthy controls:

• Organic gastrointestinal or other significant systemic disease, including cardiovascular, dermatological, psychiatric, neurological and endocrine diseases. Patients with peptic ulcer scars are also excluded.
• Chronic or acute pain, except related to other functional syndromes (irritable bowel syndrome, chronic pelvic pain, fibromyalgia, migraine).
• H. pylori positive.
• Abdominal surgery, including gastric resection or cholecystectomy (except appendectomy)
• History of brain disease or brain surgery.
• Ongoing treatment with any drugs or need for drugs (or complementary medication) within last 14 days.
• Treatment with any investigational drug during the preceding 30 days.
• Ingestion of spicy, chilli pepper containing meal, or use of capsaicin skin cream in last 48 hours before start of study or any study day.
• Pregnancy or lactation.
• No written informed consent obtained from subject.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1, FD patients; Eighty male and female FD patients according to Rome III criteria (Drossman, 2006), aged 18 to 70 years, will be recruited from primary and secondary care via advertisements and our referral networks	Procedure: gastric capsaicin with heterotopic stimulation/ distraction; The subjects are randomized to swallow either a capsaicin 0.50mg capsule or an identical placebo capsule with 100ml of water If after 15 minutes pain scores do not reach a minimum level of 30, a further double-blinded capsule of the same content will be swallowed with 100ml of water. This is repeated to a maximum of 8 capusles until pain with VAS >30 is reported.
Experimental: 2,Healthy controls; Forty male and female healthy volunteers, 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 will be recruited.	Procedure: gastric capsaicin with heterotopic stimulation/ distraction; The subjects are randomized to swallow either a capsaicin 0.50mg capsule or an identical placebo capsule with 100ml of water If after 15 minutes pain scores do not reach a minimum level of 30, a further double-blinded capsule of the same content will be swallowed with 100ml of water. This is repeated to a maximum of 8 capusles until pain with VAS >30 is reported.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Differences between healthy controls and FD subjects in visceral pain scores.	within 2 hours of Capsaicin challenge

Collaborators and Investigators

• Sponsor: National University Hospital, Singapore
• Collaborators: NMRC, Singapore

Study record dates

Study Major Dates

• Study Start: September 1, 2008
• Primary Completion (Actual): September 1, 2011
• Study Completion (Actual): September 1, 2012

Study Registration Dates

• First Submitted: June 5, 2008
• First Submitted That Met QC Criteria: June 6, 2008
• First Posted (Estimate): June 9, 2008

Study Record Updates

• Last Update Posted (Estimate): January 7, 2014
• Last Update Submitted That Met QC Criteria: January 6, 2014
• Last Verified: January 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Dyspepsia; Physiological Effects of Drugs; Peripheral Nervous System Agents; Sensory System Agents; Dermatologic Agents; Antipruritics; Capsaicin
• Other Study ID Numbers: D/07/088