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

NCT03017768 | Completed

• 1 other identifier: S57087
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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.

Conditions

Esophageal Sensitivity

Keywords

Acute tryptophan depletion, esophageal sensitivity,

Outcome Measures

Primary Outcomes (4)

• Measurement of changes in esophageal sensitivity after acute tryptophan depletion assessed by multimodal esophageal stimulation protocol

  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 sessions per HV with at least one week interval, duration of each session: approximately 7 hours. Temperature stimulation: 30 minutes

• Measurement of changes in esophageal sensitivity after acute tryptophan depletion

  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.

  2 sessions per HV with at least one week interval, duration of each session: approximately 7 hours. Mechanical stimulation: 30 minutes

• Measurement of changes in esophageal sensitivity after acute tryptophan depletion

  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.

  2 sessions per HV with at least one week interval, duration of each session: approximately 7 hours. Electrical stimulation: 30 minutes

• Measurement of changes in esophageal sensitivity after acute tryptophan depletion

  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.

  2 sessions per HV with at least one week interval, duration of each session: approximately 7 hours. Chemical stimulation: 30 minutes

Study Arms (2)

Acute tryptophan depletion

ACTIVE COMPARATOR

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; Device: Multimodal stimulation probe

Placebo

PLACEBO COMPARATOR

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; Device: Multimodal stimulation probe

Interventions

Acute tryptophan depletion DIETARY_SUPPLEMENT

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

Acute tryptophan depletion

Placebo DIETARY_SUPPLEMENT

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

Placebo

Multimodal stimulation probe DEVICE

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.

Acute tryptophan depletion; Placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• \- Age between 18 and 60 years old

You may not qualify if:

• 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.

Sponsors & Collaborators

• Universitaire Ziekenhuizen KU Leuven: lead

Study Sites (1)

Targid, KU Leuven

Leuven, Vlaams-Brabant, 3000, Belgium

Location

Study Officials

• Jan Tack, M.D., PhD

  TARGID, KU Leuven

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: December 21, 2016
• First Posted: January 11, 2017
• Study Start: June 1, 2016
• Primary Completion: March 24, 2017
• Study Completion: March 24, 2017
• Last Updated: June 28, 2017

Record last verified: 2016-12

Locations

BE (1)