We would like to modulate the serotonin system with acute tryptophan depletion (ATD) and 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…
ID
Source
Brief title
Condition
- Gastrointestinal motility and defaecation conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary aim is to assess intestinal permeability under altered serotonergic
conditions by means of sugar permeability test
Secondary outcome
Secondary outcomes of the study are to assess tight junction functionality and
serotonin metabolism in duodenal biopsy specimens and to assess visceral
hypersensitivity under altered serotoninergic conditions by the rectal barostat
method. To assess intestinal permeability and serotonin metabolism in ex vivo
Ussing chambers.
Background summary
Serotonin, 5-hydroxytryptamin (5-HT), plays an important role in regulating the
gastrointestinal functions. We postulate, that it also influences gut
permeability and visceral perception and that these changes are linked to one
another.
Study objective
We would like to modulate the serotonin system with acute tryptophan depletion
(ATD) and 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, its
oral ingestion is expected to result inan increased serotonin level. During
these interventions, gut permeability and visceral perception will be measured.
Study design
This study is a double-blind placebo-controlled study.
Intervention
Acute tryptohan depletion will be applied to decrease serotonin levels.
Administration of 5-HTP will be employed to increase serotonin levels.
Study burden and risks
Depending on which study group the participant is in, the risk and the extent
of burden differs. In the ATD group , we can expect mild side effects of the
amino acid drink itself, which do not last longer than 24-48 hours.
Furthermore, the participants will undergo a gastroduodenoscopy twice. This
procedure is generally excepted in medical pratice and considered safe with a
perforation rate of 0.03%. In de 5-HTP group, we can also expect some mild side
effects, and the participant will undergo a gastroduodenoscopy twice and a
barostat measurement also twice. The barostat measurement is also used in
everyday medical practice and there are no risks associated with this
procedure.
P.O. Box 5800
6202 AZ
NL
P.O. Box 5800
6202 AZ
NL
Listed location countries
Age
Inclusion criteria
IBS-patients
Inclusion criteria:
1) IBS will be diagnosed according to the Rome III criteria*:
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:
1) Based on medical history and previous examination, no gastrointestinal complaints can be defined.
2) Age between 18 and 65 years
Exclusion criteria
Exclusion criteria for IBS patients:;1) History of psychiatric disorders including use of psychoactive medication or psychological symptomatology, defined as a diagnosis on the 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) Inability to stop medication that can influence gastrointestinal motility or perception (like loperamide, butylscopolamine, psylliumsead (metamucil), duspatal, metoclopramide, domperidon, erytromycine), or serotonin metabolism (carbidopa, food supplementation) for at least 3 days before tests.
3) Administration of investigational drugs in the 180 days prior to the study
4) Major abdominal surgery interfering with gastrointestinal function (uncomplicated appendectomy, cholecystectomy and hysterectomy allowed, and other surgery upon judgement of the principle investigator)
5) Premenstrual syndrome, dieting (medically prescribed, vegetarian, diabetic, macrobiological, biological dynamic), 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;Exclusion criteria for healthy individuals:
1) History of psychiatric disorders including use of psychoactive medication or psychological symptomatology, defined as a diagnosis on the 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) Major abdominal surgery interfering with gastrointestinal function (uncomplicated appendectomy, laparoscopic cholecystectomy and hysterectomy allowed, and other surgery upon judgement of principle investigator)
5) Premenstrual syndrome, dieting (medically prescribed, vegetarian, diabetic, macrobiological, biological dynamic), 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
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
Register | ID |
---|---|
EudraCT | EUCTR2008-004989-11-NL |
ClinicalTrials.gov | NCT00731003 |
CCMO | NL24459.068.08 |