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

NCT ID: NCT00731003

Last Updated: 2014-11-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-04-30

Study Completion Date

2011-05-31

Brief Summary

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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.

Detailed Description

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Conditions

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Irritable Bowel Syndrome

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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I

ATD procedure

Group Type EXPERIMENTAL

Acute tryptophan depletion

Intervention Type 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.

II

Oxitriptan

Group Type EXPERIMENTAL

Oxitriptan

Intervention Type DRUG

100 mg 5-Hydroxytryptophan will be administered orally.

III

Amino acid mixture with tryptophan

Group Type PLACEBO_COMPARATOR

Amino acid drink with tryptophan

Intervention Type OTHER

Amino acid drink with tryptophan, placebo for the ATD procedure

IV

Placebo capsule

Group Type PLACEBO_COMPARATOR

Placebo capsule

Intervention Type DRUG

Placebo for 5-HTP

Interventions

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Oxitriptan

100 mg 5-Hydroxytryptophan will be administered orally.

Intervention Type DRUG

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.

Intervention Type OTHER

Amino acid drink with tryptophan

Amino acid drink with tryptophan, placebo for the ATD procedure

Intervention Type OTHER

Placebo capsule

Placebo for 5-HTP

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* IBS-patients


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


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

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


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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Top Institute Food and Nutrition

OTHER

Sponsor Role collaborator

Maastricht University Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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A AM Masclee, Prof. Dr.

Role: PRINCIPAL_INVESTIGATOR

Maastricht University Hospital

F Troost, PhD

Role: PRINCIPAL_INVESTIGATOR

Maastricht University

Locations

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Maastricht University Medical Center+

Maastricht, Limburg, Netherlands

Site Status

Countries

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Netherlands

References

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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.

Reference Type RESULT
PMID: 24943480 (View on PubMed)

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.

Reference Type RESULT
PMID: 23731747 (View on PubMed)

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.

Reference Type RESULT
PMID: 22301931 (View on PubMed)

Other Identifiers

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MEC 08-2-070

Identifier Type: -

Identifier Source: org_study_id