IG vs ID Bitter Administration

NCT03985865 | Completed Phase 4

• 1 other identifier: S551166
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

We want to investigate whether bitter compounds, denatonium benzoate and quinine hydrochloride, have a distinct effect on gastrointestinal hormone release after infusion into the stomach or duodenum. Furthermore, we want to observe an effect on hunger sensations and hedonic food intake. Moreover, we suggest somatostatin as a driving factor for decreased motilin and ghrelin release after intragastric administration.

Conditions

Obesity

Keywords

Bitter; Motilin; Ghrelin; CCK; GLP-1; SST; Denatonium benzoate; Quinine hydrochloride

Outcome Measures

Primary Outcomes (1)

• Changes in plasma levels of motilin, ghrelin, somatostatin, GLP-1 and CCK after bitter administration into the stomach or duodenum

  Infusion of bitter compounds into the stomach or duodenum is performed via a nasogastric feeding tube. Afterwards, an intravenous dwelling line is placed to take blood samples at several time points during the experiment. Hormone levels of motilin, ghrelin, somatostatin, GLP-1 and CCK are collected with according enzyme inhibitors.

  A first blood sample is taken as a reference 10 min before administration of the condition. After the infusion, every 10 min blood samples are taken for 2 hours.

Secondary Outcomes (2)

• Changes in hunger scores after bitter administration into the stomach or duodenum

  Hunger is scored every 10 min during the whole experiment starting 20 min before the infusion, until 2 hours after the infusion. 1 minute before and after ad libitum drinking, hunger is scored.

• Changes in hedonic food intake after bitter administration into the stomach or duodenum

  2 hours after the infusion of a condition, subjects drink from the milkshake without an intermission.

Study Arms (6)

Intragastric quinine hydrochloride

EXPERIMENTAL

10 µmol of quinine hydrochloride per kg body weight was administrated into the stomach.

Drug: Intragastric quinine hydrochloride

intragastric denatonium benzoate

EXPERIMENTAL

1 µmol of denatonium benzoate per kg body weight was administrated into the stomach.

Drug: Intragastric denatonium benzoate

Intragastric placebo

PLACEBO COMPARATOR

0.1 ml of water (placebo) per kg body weight was administrated into the stomach.

Drug: Intragastric placebo

Intraduodenal quinine hydrochloride

EXPERIMENTAL

10 µmol of quinine hydrochloride per kg body weight was administrated into the duodenum.

Drug: Intraduodenal quinine hydrochloride

Intraduodenal denatonium benzoate

EXPERIMENTAL

1 µmol of denatonium benzoate per kg body weight was administrated into the duodenum.

Drug: Intraduodenal denatonium benzoate

Intraduodenal placebo

PLACEBO COMPARATOR

0.1 ml of water (placebo) per kg body weight was administrated into the duodenum.

Drug: Intraduodenal placebo

Interventions

Intragastric quinine hydrochloride DRUG

A nasogastric feeding tube was positioned into the stomach, and checked with a pH strip. 10 µmol of quinine hydrochloride per kg body weight was administrated into the stomach.

Also known as: IG QHCl

Intragastric quinine hydrochloride

Intragastric denatonium benzoate DRUG

A nasogastric feeding tube was positioned into the stomach, and checked with a pH strip. 1 µmol of denatonium benzoate per kg body weight was administrated into the stomach.

Also known as: IG DB

intragastric denatonium benzoate

Intragastric placebo DRUG

A nasogastric feeding tube was positioned into the stomach, and checked with a pH strip. 0.1 ml of water (placebo) per kg body weight was administrated into the stomach.

Also known as: IG PLC

Intragastric placebo

Intraduodenal quinine hydrochloride DRUG

A nasogastric feeding tube was positioned into the duodenum, and checked with fluoroscopy. 10 µmol of quinine hydrochloride per kg body weight was administrated into the duodenum.

Also known as: ID QHCl

Intraduodenal quinine hydrochloride

Intraduodenal denatonium benzoate DRUG

A nasogastric feeding tube was positioned into the duodenum, and checked with fluoroscopy. 1 µmol of denatonium benzoate per kg body weight was administrated into the duodenum.

Also known as: IG DB

Intraduodenal denatonium benzoate

Intraduodenal placebo DRUG

A nasogastric feeding tube was positioned into the duodenum, and checked with fluoroscopy. 0.1 ml of water (placebo) per kg body weight was administrated into the duodenum.

Also known as: ID PLC

Intraduodenal placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Gender Eligibility Details: Female volunteers have a higher chance to be more sensitive for bitter compounds because of their genetic background in comparison to males.
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject is female between 18 and 65 years of age.
• Subject has a BMI between 18 and 25 kg/m² and has a stable body weight for at least 3 consecutive months at the start of the study and keeps a stable weight during the study visits.
• Women of child-bearing potential agree to apply during the entire duration of the trial a highly effective method of birth control, which is defined as those which result in a low failure rate (i.e., less than 1% per year) when used constantly and correctly such as implants, injectables, combined oral contraceptive method, or some intrauterine devices (IUDs), sexual abstinence, or vasectomized partner. Women of non-childbearing potential may be included if surgically sterile (tubal ligation or hysterectomy) or postmenopausal with at least 2 year without spontaneous menses.
• Subject understands the study procedures and agrees to participate in the study by giving written informed consent.

You may not qualify if:

• Subject is under age of legal consent, male, pregnant or breastfeeding.
• Subject with a BMI ≥ 18 kg/m² or BMI ≤ 25 kg/m².
• Subject has current symptoms or a history of gastrointestinal or other significant somatic or psychiatric diseases or drug allergies.
• Subject has diabetes.
• Subject has a significant heart, lung, liver or kidney disease.
• Subject has any history of a neurological disorder.
• Subject has a history of abdominal surgery. Those having undergone a simple appendectomy more than 1 year prior to the screening visit may participate.
• Subject shows abnormal eating behavior or has an eating disorder.
• History or current use of drugs that can affect glycaemia, gastrointestinal function, motility or sensitivity or gastric acidity.
• History or current use of centrally acting medication, including antidepressants, antipsychotics and/or benzodiazepines (in the last year before screening visit).
• Subject consumes excessive amounts of alcohol, defined as \>14 units per week.
• Subject is currently (defined as within approximately 1 year of the screening visit) a regular or irregular user (including "recreational use") of any illicit drugs (including marijuana) or has a history of drug (including alcohol) abuse. Further, patient is unwilling to refrain from the use of drugs during this study.
• High caffeine intake (\> 500 ml coffee daily or equivalent).
• Inability or unwillingness to perform all of the study procedures, or the subject is considered unsuitable in any way by the principal investigator.
• Recent participation (\<30 days) or simultaneous participation in another clinical study.

Sponsors & Collaborators

• Universitaire Ziekenhuizen KU Leuven: lead

Study Sites (1)

TARGID

Leuven, Vlaams-Brabant, 3000, Belgium

Location

Related Publications (1)

• Verbeure W, Deloose E, Toth J, Rehfeld JF, Van Oudenhove L, Depoortere I, Tack J. The endocrine effects of bitter tastant administration in the gastrointestinal system: intragastric versus intraduodenal administration. Am J Physiol Endocrinol Metab. 2021 Jul 1;321(1):E1-E10. doi: 10.1152/ajpendo.00636.2020. Epub 2021 May 24.

  PMID: 34029163 DERIVED

MeSH Terms

Conditions

Obesity

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Jan Tack

  UZ Leuven

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 11, 2019
• First Posted: June 14, 2019
• Study Start: March 2, 2017
• Primary Completion: May 7, 2018
• Study Completion: May 7, 2018
• Last Updated: June 14, 2019

Record last verified: 2019-01

Locations

BE (1)