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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified February 2011 by Maastricht University Medical Center.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Top Institute Food and Nutrition
Information provided by:
Maastricht University Medical Center
ClinicalTrials.gov Identifier:
NCT00731003
First received: August 4, 2008
Last updated: February 16, 2011
Last verified: February 2011
  Purpose

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.


Condition Intervention
Irritable Bowel Syndrome
Drug: Oxitriptan
Other: Acute tryptophan depletion
Other: Amino acid drink with tryptophan
Drug: Placebo capsule

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Basic Science
Official Title: The Effect of Serotonergic Modulation on Intestinal Permeability and Visceral Hypersensitivity in Healthy Individuals and IBS Patients

Resource links provided by NLM:


Further study details as provided by Maastricht University Medical Center:

Primary Outcome Measures:
  • The primary aim is to assess intestinal permeability under altered serotonergic conditions by means of sugar permeability test [ Time Frame: 2010 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Estimated Enrollment: 60
Study Start Date: April 2009
Estimated Study Completion Date: May 2011
Estimated Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00731003

Contacts
Contact: D Keszthelyi, MD daniel.keszthelyi@intmed.unimaas.nl

Locations
Netherlands
Maastricht University Medical Center+ Recruiting
Maastricht, Limburg, Netherlands, 6200AZ
Contact: Daniel Keszthelyi, MD    0031433881982    daniel.keszthelyi@intmed.unimaas.nl   
Sponsors and Collaborators
Maastricht University Medical Center
Top Institute Food and Nutrition
Investigators
Principal Investigator: A AM Masclee, Prof. Dr. Maastricht University Hospital
Principal Investigator: F Troost, PhD Maastricht University
  More Information

No publications provided by Maastricht University Medical Center

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Prof. Dr. A. Masclee, Maastricht University
ClinicalTrials.gov Identifier: NCT00731003     History of Changes
Other Study ID Numbers: MEC 08-2-070
Study First Received: August 4, 2008
Last Updated: February 16, 2011
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Maastricht University Medical Center:
serotonin
gut permeability
visceral sensitivity
irritable bowel syndrome

Additional relevant MeSH terms:
Irritable Bowel Syndrome
Syndrome
Hypersensitivity
Colonic Diseases, Functional
Colonic Diseases
Intestinal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Disease
Pathologic Processes
Immune System Diseases
Tryptophan
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 20, 2014