IG vs ID Bitter Administration

NCT ID: NCT03985865

Last Updated: 2019-06-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 14 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-03-02
• Study Completion Date: 2018-05-07

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.

Detailed Description

Intragastric administration of the bitter tastants denatonium benzoate (DB) or quinine hydrochloride (QHCl) decreases orexigenic hormone levels, and reduces hunger sensations. Contradictory, in vitro studies on human gastric and duodenal tissue showed that DB exposure increased motilin and octanoylated ghrelin levels. DB stimulated somatostatin (SST) release, which is an inhibiting paracrine hormone. We hypothesized that the reduction in hunger ratings and hormone levels is stronger after intragastric compared to intraduodenal administration, and that these differences are mediated by differential SST release. Fourteen healthy female volunteers participated in a randomized, placebo-controlled crossover study. After an overnight fast, DB (1 µmol/kg), QHCl (10 µmol/kg) or placebo were given intragastric or intraduodenal via a feeding tube. Blood samples were taken at regular time points to obtain the hormonal release. Hunger was rated at the same points on a 100 mm visual analog scale (VAS). Ad libitum milkshake intake was assessed at the end of the experiment and taste was scored on a VAS.

Conditions

Obesity

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: SINGLE

Study Groups

Intragastric quinine hydrochloride

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

Group Type: EXPERIMENTAL

Intragastric quinine hydrochloride

Intervention Type: 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.

intragastric denatonium benzoate

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

Group Type: EXPERIMENTAL

Intragastric denatonium benzoate

Intervention Type: 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.

Intragastric placebo

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

Group Type: PLACEBO_COMPARATOR

Intragastric placebo

Intervention Type: 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.

Intraduodenal quinine hydrochloride

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

Group Type: EXPERIMENTAL

Intraduodenal quinine hydrochloride

Intervention Type: 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.

Intraduodenal denatonium benzoate

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

Group Type: EXPERIMENTAL

Intraduodenal denatonium benzoate

Intervention Type: 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.

Intraduodenal placebo

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

Group Type: PLACEBO_COMPARATOR

Intraduodenal placebo

Intervention Type: 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.

Interventions

Intragastric quinine hydrochloride

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.

Intervention Type: DRUG

Intragastric denatonium benzoate

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.

Intervention Type: DRUG

Intragastric placebo

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.

Intervention Type: DRUG

Intraduodenal quinine hydrochloride

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.

Intervention Type: DRUG

Intraduodenal denatonium benzoate

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.

Intervention Type: DRUG

Intraduodenal placebo

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.

Intervention Type: DRUG

Other Intervention Names

IG QHCl; IG DB; IG PLC; ID QHCl; IG DB; ID PLC

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.
• Subjects with lactose intolerance.
• Subjects with quinine allergy.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Universitaire Ziekenhuizen KU Leuven

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jan Tack

Role: PRINCIPAL_INVESTIGATOR

UZ Leuven

Locations

TARGID

Leuven, Vlaams-Brabant, Belgium

Countries

Belgium

References

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.

Reference Type: DERIVED

PMID: 34029163 (View on PubMed)

Other Identifiers

S551166

Identifier Type: -

Identifier Source: org_study_id