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Completed

NCT Number: NCT00731003

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

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Key information

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Maastricht University Medical Center+

Maastricht, Limburg, 6200AZ, Netherlands

Who can participate

Healthy volunteers accepted: Yes

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

Inclusion criteria

  • IBS-patients

Inclusion criteria

  • 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.
  • Based on the medical history and previous examination, no other causes for the abdominal complaints can be defined.
  • 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:
  • Severe co-morbidity hindering a rectal barostat procedure, according to the gastroenterologist's perception.
  • Abdominal surgery, except for uncomplicated appendectomy, laparoscopic cholecystectomy or hysterectomy.
  • 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.
  • 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
  • Administration of investigational drugs in the 180 days prior to the study
  • Premenstrual syndrome, dieting, pregnancy, lactation
  • Excessive alcohol consumption (>20 alcoholic consumption per week)
  • Smoking
  • Blood donation within 3 months before the study period
  • Self-admitted HIV-positive state
  • Irregular day-night rhythm

Exclusion criteria

for healthy individuals:

  • 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
  • Use of medication, except oral contraceptives, within 14 days prior to testing
  • Administration of investigational drugs in the 180 days prior to the study
  • Previous abdominal surgery (other than uncomplicated appendectomy, laparoscopic cholecystectomy and hysterectomy)
  • Premenstrual syndrome, dieting, pregnancy, lactation
  • Excessive alcohol consumption (>20 alcoholic consumption per week)
  • Smoking
  • Blood donation within 3 months before the study period
  • Self-admitted HIV-positive state
  • Irregular day-night rhythm
  • Severe co-morbidity hindering a rectal barostat procedure, according to the gastroenterologist's perception.

Treatment and study plan

Oxitriptan

Drug

100 mg 5-Hydroxytryptophan will be administered orally.

Acute tryptophan depletion

Other

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.

Amino acid drink with tryptophan

Other

Amino acid drink with tryptophan, placebo for the ATD procedure

Placebo capsule

Drug

Placebo for 5-HTP

Primary outcomes

  1. The primary aim is to assess intestinal permeability under altered serotonergic conditions by means of sugar permeability test

    Time frame: 2010

Secondary outcomes

  1. 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

Sponsors and collaborators

Lead sponsor

Maastricht University Medical Center

Other

Collaborators

  • Top Institute Food and Nutrition

Registry information

Official study title

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

Important dates

Study start
2009
Primary completion
2011
Study completion
2011
First posted
Aug 8, 2008
Registry last updated
Nov 13, 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.

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