Irritable Bowel SyndromeNCT00731003
The Effect of Serotonergic Modulation on Intestinal Permeability and Visceral Hypersensitivity in Healthy Individuals and Irritable Bowel Syndrome (IBS) Patients
A study testing Oxitriptan, Acute tryptophan depletion and Amino acid drink with tryptophan in people with Irritable Bowel Syndrome, run by Maastricht University Medical Center at 1 site in Netherlands.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Irritable Bowel Syndrome
- What is being tested?
- Oxitriptan, Acute tryptophan depletion and Amino acid drink with tryptophan
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteNetherlands
- Study dates
- Apr 2009to May 2011
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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
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- 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)
- 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.
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Maastricht University Medical Center+
Maastricht, Limburg, 6200AZ
About this study
Official title: 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.
- Conditions
- Irritable Bowel Syndrome
- Being tested
- Oxitriptan, Acute tryptophan depletion, Amino acid drink with tryptophan, Placebo capsule
- Keywords
- serotonin, gut permeability, visceral sensitivity, irritable bowel syndrome
- Medical subject headings
- Irritable Bowel Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OxitriptanDrug
100 mg 5-Hydroxytryptophan will be administered orally.
Acute tryptophan depletionOther
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 tryptophanOther
Amino acid drink with tryptophan, placebo for the ATD procedure
Placebo capsuleDrug
Placebo for 5-HTP
| Study group | Role | What they receive |
|---|---|---|
| I | Experimental | ATD procedure Receives: Other: Acute tryptophan depletion |
| II | Experimental | Oxitriptan Receives: Drug: Oxitriptan |
| III | Placebo comparator | Amino acid mixture with tryptophan Receives: Other: Amino acid drink with tryptophan |
| IV | Placebo comparator | Placebo capsule Receives: Drug: Placebo capsule |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary aim is to assess intestinal permeability under altered serotonergic conditions by means of sugar permeability test
Measured: 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
Measured: 2010
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Aug 2008 (estimated)
- Study startApr 2009
- Primary completionMay 2011
- Study completionMay 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Irritable Bowel SyndromeStudies of the same condition, open and under way.
- More trials run by Maastricht University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Maastricht University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Top Institute Food and Nutrition
- Responsible party
- Sponsor
- Investigators
- A AM Masclee, Prof. Dr., Principal investigator, Maastricht University HospitalF Troost, PhD, Principal investigator, Maastricht University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00731003
- Sponsor's protocol ID
- MEC 08-2-070
- Status last verified
- Nov 2014
- First submitted
- 4 Aug 2008
- Last updated
- 13 Nov 2014
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 24943480Keszthelyi 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.
PubMed 23731747Keszthelyi 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.
PubMed 22301931
Study at a glance
From the registry record, last updated by the sponsor on 13 Nov 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Serotonergic Modulation on Intestinal Permeability and Visceral Hypersensitivity in Healthy Individuals and IBS Patients
- ClinicalTrials.gov ID
- NCT00731003
- Acronym / sponsor ID
- MEC 08-2-070
- Conditions
- Irritable Bowel Syndrome
- Keywords
- serotonin, gut permeability, visceral sensitivity, irritable bowel syndrome
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Maastricht University Medical CenterUniversity, hospital or other
- Collaborators
- Top Institute Food and Nutrition
- Study start
- Apr 2009
- Primary completion
- May 2011 (actual)
- Study completion
- May 2011 (actual)
- First posted
- 8 Aug 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| I | Experimental | Other: Acute tryptophan depletionATD procedure |
| II | Experimental | Drug: OxitriptanOxitriptan |
| III | Placebo comparator | Other: Amino acid drink with tryptophanAmino acid mixture with tryptophan |
| IV | Placebo comparator | Drug: Placebo capsulePlacebo capsule |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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:
- Based on the medical history and previous examination, no other causes for the abdominal complaints can be defined.
- Age between 18 and 65 years
Key exclusion criteria (22 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Oxitriptan100 mg 5-Hydroxytryptophan will be administered orally. | Drug | II |
| Acute tryptophan depletionAcute tryptophan depletion employs the oral ingestion of an amino acid mixture devoid of tryptophan, the precursor of serotonin, which results in lowered serotonin levels. | Other | I |
| Amino acid drink with tryptophanAmino acid drink with tryptophan, placebo for the ATD procedure | Other | III |
| Placebo capsulePlacebo for 5-HTP | Drug | IV |
Primary outcome
The primary aim is to assess intestinal permeability under altered serotonergic conditions by means of sugar permeability test
Time frame: 2010
1 secondary outcome
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Nov 2014.
- Results publication: PubMed 24943480Keszthelyi 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.
- Results publication: PubMed 23731747Keszthelyi 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.
- Results publication: PubMed 22301931Keszthelyi 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
A AM Masclee, Prof. Dr. principal investigator
Maastricht University Hospital
F Troost, PhD principal investigator
Maastricht University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Oxitriptan, Acute tryptophan depletion and Amino acid drink with tryptophan in people with Irritable Bowel Syndrome, run by Maastricht University Medical Center at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Nov 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The primary aim is to assess intestinal permeability under altered serotonergic conditions by means of sugar permeability test (time frame: 2010). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00731003, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Nov 2014.