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

NCT00731003 | Completed DMC

• 1 other identifier: MEC 08-2-070
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Irritable Bowel Syndrome

Keywords

serotonin; gut permeability; visceral sensitivity; irritable bowel syndrome

Outcome Measures

Primary Outcomes (1)

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

  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

  2010

Study Arms (4)

I

EXPERIMENTAL

ATD procedure

Other: Acute tryptophan depletion

II

EXPERIMENTAL

Oxitriptan

Drug: Oxitriptan

III

PLACEBO COMPARATOR

Amino acid mixture with tryptophan

Other: Amino acid drink with tryptophan

IV

PLACEBO COMPARATOR

Placebo capsule

Drug: Placebo capsule

Interventions

Oxitriptan DRUG

100 mg 5-Hydroxytryptophan will be administered orally.

II

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.

I

Amino acid drink with tryptophan OTHER

Amino acid drink with tryptophan, placebo for the ATD procedure

III

Placebo capsule DRUG

Placebo for 5-HTP

IV

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• IBS-patients
• 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
• 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.

You may not qualify if:

• 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
• 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)

Sponsors & Collaborators

• Maastricht University Medical Center: lead
• Top Institute Food and Nutrition: collaborator

Study Sites (1)

Maastricht University Medical Center+

Maastricht, Limburg, 6200AZ, Netherlands

Location

Related Publications (3)

• Keszthelyi D, Troost FJ, Jonkers DM, van Eijk HM, Lindsey PJ, Dekker J, Buurman WA, Masclee AA. Serotonergic reinforcement of intestinal barrier function is impaired in irritable bowel syndrome. Aliment Pharmacol Ther. 2014 Aug;40(4):392-402. doi: 10.1111/apt.12842. Epub 2014 Jun 18.

  PMID: 24943480 RESULT

• Keszthelyi D, Troost FJ, Jonkers DM, Kruimel JW, Leue C, Masclee AA. Decreased levels of kynurenic acid in the intestinal mucosa of IBS patients: relation to serotonin and psychological state. J Psychosom Res. 2013 Jun;74(6):501-4. doi: 10.1016/j.jpsychores.2013.01.008. Epub 2013 Feb 15.

  PMID: 23731747 RESULT

• Keszthelyi D, Troost FJ, Jonkers DM, van Donkelaar EL, Dekker J, Buurman WA, Masclee AA. Does acute tryptophan depletion affect peripheral serotonin metabolism in the intestine? Am J Clin Nutr. 2012 Mar;95(3):603-8. doi: 10.3945/ajcn.111.028589. Epub 2012 Feb 1.

  PMID: 22301931 RESULT

MeSH Terms

Conditions

Irritable Bowel Syndrome

Interventions

5-Hydroxytryptophan; Tryptophan

Condition Hierarchy (Ancestors)

Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Essential

Study Officials

• A AM Masclee, Prof. Dr.

  Maastricht University Hospital

  PRINCIPAL INVESTIGATOR

• F Troost, PhD

  Maastricht University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 4, 2008
• First Posted: August 8, 2008
• Study Start: April 1, 2009
• Primary Completion: May 1, 2011
• Study Completion: May 1, 2011
• Last Updated: November 13, 2014

Record last verified: 2014-11

Locations

NL (1)