Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

The Effect of Acute Tryptophan Depletion (ATD) on Esophageal Sensitivity in Healthy Volunteers

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03017768
Recruitment Status : Completed
First Posted : January 11, 2017
Last Update Posted : June 28, 2017
Sponsor:
Information provided by (Responsible Party):
Universitaire Ziekenhuizen Leuven

Brief Summary:

Esophageal hypersensitivity is considered an important pathophysiological mechanism in patients suffering form non-erosive gastro-esophageal reflux disease. Serotonin (5-HT) is predominantly found in the central nervous system and in the gastro-intestinal (GI) tract. 5-HT plays a major role in the regulation of GI secretion, motility and sensitivity, and has been associated with emotion regulation. Acute tryptophan depletion (ATD) temporarily reduces the availability of tryptophan (TRP), thereby decreasing central and peripheral 5-HT synthesis. From previous studies, ATD is known to affect GI physiology and enhance visceral pain perception in the colon. The aim of the study was to investigate the effect of ATD on esophageal sensitivity in healthy volunteers (HV).

Esophageal multimodal sensitivity was assessed after intragastric infusion of an amino-acid mixture (AA-mix) containing 15 AAs with TRP (control condition) or without TRP (ATD condition). After an incubation period of 5 hours, a probe with a polyurethane bag was positioned in the distal esophagus. Thermal (recirculating a heated saline solution through the bag), mechanical (increasing bag volume), electrical (2 stimulation electrodes) and chemical sensitivity (modified Bernstein) were tested and at 3 time points blood samples were collected for biochemical analysis. General mood was assessed by the Positive and Negative Affect Schedule (PANAS) and the State-Trait Anxiety Inventory (STAI) questionnaires.


Condition or disease Intervention/treatment Phase
Esophageal Sensitivity Dietary Supplement: Acute tryptophan depletion Dietary Supplement: Placebo Device: Multimodal stimulation probe Not Applicable

Show Show detailed description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 15 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single (Participant)
Primary Purpose: Basic Science
Official Title: The Effect of Acute Tryptophan Depletion (ATD) on Esophageal Sensitivity in Healthy Volunteers: a Randomized, Single-blind, Placebo-controlled Study
Study Start Date : June 2016
Actual Primary Completion Date : March 24, 2017
Actual Study Completion Date : March 24, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Allergy
Drug Information available for: Tryptophan

Arm Intervention/treatment
Active Comparator: Acute tryptophan depletion
Administration of an amino acid mixture consisting of 15 amino acids, (4.1g L-alanine, 2.4g glycine, 2.4g L-histidine, 6.0g L-isoleucine, 10.1g L-leucine, 6.7g L-lysine, 4.3g L-phenylalanine, 9.2g L-proline, 5.2g L-serine, 4.3g L-threonine, 5.2g L-tyrosine, 6.7g L-valine, 3.7g L-argine, 2.0g L-cysteine, 3.0g L-methionine) lacking tryptophan to investigate the effect of tryptophan depletion on esophageal sensitivity
Dietary Supplement: Acute tryptophan depletion
an amino-acid mixture will be administered without tryptophan (active comparator). After an incubation period of 5 hours esophageal sensitivity will be assessed by multimodal stimulation to evaluate the effect of depleted tryptophan levels on esophageal sensitivity

Device: Multimodal stimulation probe
The multimodal esophageal probe allows to perform 4 types of stimulations in the esophagus (thermal, mechanical, electrical and chemical stimulation). These 4 modalities will be evaluated to assess esophageal sensitivity.

Placebo Comparator: Placebo
Administration of an amino acid mixture consisting of 15 amino acids, (4.1g L-alanine, 2.4g glycine, 2.4g L-histidine, 6.0g L-isoleucine, 10.1g L-leucine, 6.7g L-lysine, 4.3g L-phenylalanine, 9.2g L-proline, 5.2g L-serine, 4.3g L-threonine, 5.2g L-tyrosine, 6.7g L-valine, 3.7g L-argine, 2.0g L-cysteine, 3.0g L-methionine and 3.0g L-trypyophan). Since this amino-acid mixture contains tryptophan it is used as the placebo arm of this cross-over study
Dietary Supplement: Placebo
an amino-acid mixture with tryptophan (placebo mixture) will be administered. After an incubation period of 5 hours esophageal sensitivity will be assessed by multimodal stimulation

Device: Multimodal stimulation probe
The multimodal esophageal probe allows to perform 4 types of stimulations in the esophagus (thermal, mechanical, electrical and chemical stimulation). These 4 modalities will be evaluated to assess esophageal sensitivity.




Primary Outcome Measures :
  1. Measurement of changes in esophageal sensitivity after acute tryptophan depletion assessed by multimodal esophageal stimulation protocol [ Time Frame: 2 sessions per HV with at least one week interval, duration of each session: approximately 7 hours. Temperature stimulation: 30 minutes ]
    Investigation of the effect of acute tryptophan depletion on esophageal sensitivity to multimodal stimulation in a group of healthy volunteers. This will be assessed by comparing the Temperature values (°C) of the stimulation tests between the placebo and acute tryptophan depletion condition to see if tryptophan depletion affects the sensitivity to increasing temperature.

  2. Measurement of changes in esophageal sensitivity after acute tryptophan depletion [ Time Frame: 2 sessions per HV with at least one week interval, duration of each session: approximately 7 hours. Mechanical stimulation: 30 minutes ]
    Investigation of the effect of acute tryptophan depletion on esophageal sensitivity to multimodal stimulation in a group of healthy volunteers. This will be assessed by comparing the balloon volumes (volume in ml) of the stimulation tests between the placebo and acute tryptophan depletion condition to see if tryptophan depletion affects the sensitivity to increasing balloon volume.

  3. Measurement of changes in esophageal sensitivity after acute tryptophan depletion [ Time Frame: 2 sessions per HV with at least one week interval, duration of each session: approximately 7 hours. Electrical stimulation: 30 minutes ]
    Investigation of the effect of acute tryptophan depletion on esophageal sensitivity to multimodal stimulation in a group of healthy volunteers. This will be assessed by comparing the tolerated intensity of the electrical pulses (mA) of the stimulation tests between the placebo and acute tryptophan depletion condition to see if tryptophan depletion affects the sensitivity to increasing electrical pulses.

  4. Measurement of changes in esophageal sensitivity after acute tryptophan depletion [ Time Frame: 2 sessions per HV with at least one week interval, duration of each session: approximately 7 hours. Chemical stimulation: 30 minutes ]
    Investigation of the effect of acute tryptophan depletion on esophageal sensitivity to multimodal stimulation in a group of healthy volunteers. This will be assessed by comparing the volume of infused acid (ml) of the stimulation tests between the placebo and acute tryptophan depletion condition to see if tryptophan depletion affects the sensitivity to acid infusion.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

- Age between 18 and 60 years old

Exclusion Criteria:

  • history of psychiatric disease or a positive first degree psychiatric family history,
  • pregnancy or lactation,
  • concomitant administration of any centrally activating medication
  • medication affecting esophageal motility,
  • significant co-morbidities (neuromuscular, cardiovascular, pulmonary, endocrine, autoimmune, renal and hepatic),
  • prior history of esophageal, Ear-Nose and Throat or gastric surgery or endoscopic anti-reflux procedure,
  • history of gastrointestinal disease
  • During the last two weeks before the study, the volunteers should be free from medication, except for oral contraceptives.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03017768


Locations
Layout table for location information
Belgium
Targid, KU Leuven
Leuven, Vlaams-Brabant, Belgium, 3000
Sponsors and Collaborators
Universitaire Ziekenhuizen Leuven
Investigators
Layout table for investigator information
Principal Investigator: Jan Tack, M.D., PhD TARGID, KU Leuven
Layout table for additonal information
Responsible Party: Universitaire Ziekenhuizen Leuven
ClinicalTrials.gov Identifier: NCT03017768    
Other Study ID Numbers: S57087
First Posted: January 11, 2017    Key Record Dates
Last Update Posted: June 28, 2017
Last Verified: December 2016
Keywords provided by Universitaire Ziekenhuizen Leuven:
Acute tryptophan depletion, esophageal sensitivity,
Additional relevant MeSH terms:
Layout table for MeSH terms
Hypersensitivity
Immune System Diseases
Tryptophan
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs