The Effect of Serotonergic Modulation on Intestinal Permeability and Visceral Hypersensitivity in Healthy Individuals and Irritable Bowel Syndrome (IBS) Patients

November 11, 2014 updated by: Maastricht University Medical Center

The Effect of Serotonergic Modulation on Intestinal Permeability and Visceral Hypersensitivity in Healthy Individuals and IBS Patients

Serotonin, 5-hydroxytryptamin (5-HT), plays an important role in regulating the gastrointestinal functions. In this study we will modulate the serotonin system with acute tryptophan depletion (ATD) and administration of 5-hydroxytryptophan (5-HTP). ATD is based on ingestion of an amino acid drink devoid of the precursor of serotonin and hence caused a decreased serotonin level. 5-hydroxy-tryptophan is the direct precursor of serotonin and its administration, an increased serotonin level is expected. During these interventions, gut permeability and visceral sensitivity will be measured in healthy individuals and patients with irritable bowel syndrome, which is characterized by altered permeability and visceral hypersensitivity.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

60

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
    • Limburg
      • Maastricht, Limburg, Netherlands, 6200AZ
        • Maastricht University Medical Center+

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • IBS-patients

Inclusion criteria:

  1. IBS will be diagnosed according to the Rome III criteria* [35]:

    Recurrent abdominal pain or discomfort at least 3 days per month in the last 3 months associated with 2 or more of the following:

    • Improvement with defecation
    • Onset associated with a change in frequency of stool

    • Onset associated with a change in form (appearance) of stool

      • Criteria fulfilled for the last 3 months with symptom onset at least 6 months prior to diagnosis
      • Discomfort means an uncomfortable sensation not described as pain. In pathophysiological research and clinical trails, a pain/discomfort frequency of at least 2 days a week during screening evaluation is an indication for subject's eligibility.
  2. Based on the medical history and previous examination, no other causes for the abdominal complaints can be defined.
  3. Age between 18 and 65 years

Healthy individuals

Inclusion criteria:

All subjects will be screened with a standardized psychiatric examination using the mini international neuropsychiatric interview (MINI) to determine present psychiatric state. General psychological state will be assessed using the 17 item Hamilton depression rating scale (HAM-D17), the Dutch version of the symptom checklist (SCL-90) and the hospital anxiety and depression rating scale (HADS). The psychiatric evaluation will be carried out by a psychiatrist. Volunteers with deviating scores on any topic will be excluded from participation.

Healthy individuals between age 18 and 65 years will be included in the study.

Exclusion Criteria:

  • Exclusion criteria for IBS patients:

    1. Severe co-morbidity hindering a rectal barostat procedure, according to the gastroenterologist's perception.
    2. Abdominal surgery, except for uncomplicated appendectomy, laparoscopic cholecystectomy or hysterectomy.
    3. Inability to stop medication that can influence gastrointestinal motility or perception (like loperamide, butylscopolamine, psylliumsead (metamucil), duspatal, metoclopramide, domperidon, erytromycine), or serotonin metabolism (carbidopa) for at least 3 days before tests.
    4. History of psychiatric disorders including use of psychoactive medication or psychological symptomatology, defined as a diagnosis on the MINI, HAM-D17 score above 18, global severity index score on SCL-90 for females ≥150, for males ≥131, or HADS scores ≥ 8. First-degree family members with psychiatric disorders
    5. Administration of investigational drugs in the 180 days prior to the study
    6. Premenstrual syndrome, dieting, pregnancy, lactation
    7. Excessive alcohol consumption (>20 alcoholic consumption per week)
    8. Smoking
    9. Blood donation within 3 months before the study period
    10. Self-admitted HIV-positive state
    11. Irregular day-night rhythm

Exclusion criteria for healthy individuals:

  1. History of gastrointestinal, psychiatric disorders including use of psychoactive medication or psychological symptomatology, defined as a diagnosis on the MINI, HAM-D17 score above 18, global severity index score on SCL-90 for females ≥150, for males ≥131, or HADS scores ≥ 8 First-degree family members with psychiatric disorders
  2. Use of medication, except oral contraceptives, within 14 days prior to testing
  3. Administration of investigational drugs in the 180 days prior to the study
  4. Previous abdominal surgery (other than uncomplicated appendectomy, laparoscopic cholecystectomy and hysterectomy)
  5. Premenstrual syndrome, dieting, pregnancy, lactation
  6. Excessive alcohol consumption (>20 alcoholic consumption per week)
  7. Smoking
  8. Blood donation within 3 months before the study period
  9. Self-admitted HIV-positive state
  10. Irregular day-night rhythm
  11. Severe co-morbidity hindering a rectal barostat procedure, according to the gastroenterologist's perception.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: I
ATD procedure
Other: Acute tryptophan depletion
Acute tryptophan depletion employs the oral ingestion of an amino acid mixture devoid of tryptophan, the precursor of serotonin, which results in lowered serotonin levels.
Experimental: II
Oxitriptan
Drug: Oxitriptan
100 mg 5-Hydroxytryptophan will be administered orally.
Placebo Comparator: III
Amino acid mixture with tryptophan
Other: Amino acid drink with tryptophan
Amino acid drink with tryptophan, placebo for the ATD procedure
Placebo Comparator: IV
Placebo capsule
Drug: Placebo capsule
Placebo for 5-HTP

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
The primary aim is to assess intestinal permeability under altered serotonergic conditions by means of sugar permeability test
Time Frame: 2010
2010

Secondary Outcome Measures

Outcome Measure
Time Frame
To assess tight junction functionality and serotonin metabolism To assess visceral hypersensitivity under altered serotoninergic conditions To examine biopsy specimens for serotonergic and intestinal permeability parameters in ex vivo circumstances
Time Frame: 2010
2010

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Maastricht University Medical Center

Collaborators

Top Institute Food and Nutrition

Investigators

  • Principal Investigator: A AM Masclee, Prof. Dr., Maastricht University Hospital
  • Principal Investigator: F Troost, PhD, Maastricht University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2009

Primary Completion (Actual)

May 1, 2011

Study Completion (Actual)

May 1, 2011

Study Registration Dates

First Submitted

August 4, 2008

First Submitted That Met QC Criteria

August 7, 2008

First Posted (Estimate)

August 8, 2008

Study Record Updates

Last Update Posted (Estimate)

November 13, 2014

Last Update Submitted That Met QC Criteria

November 11, 2014

Last Verified

November 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MEC 08-2-070

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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