ObesityPhase 4IG vs IDNCT03985865
IG vs ID Bitter Administration
A Phase 4 study testing Intragastric quinine hydrochloride, Intragastric denatonium benzoate and Intraduodenal quinine hydrochloride in people with Obesity, run by Universitaire Ziekenhuizen KU Leuven at 1 site in Belgium.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Obesity
- What is being tested?
- Intragastric quinine hydrochloride, Intragastric denatonium benzoate and Intraduodenal quinine hydrochloride
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 14 participants
- Where
- 1 siteBelgium
- Study dates
- 2 Mar 2017to 7 May 2018
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 17Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Influence of Bitter Substrates on Hunger, Gastrointestinal Hormone Release and Hedonic Food Intake
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.
Read the 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
- Being tested
- Intragastric quinine hydrochloride, Intragastric denatonium benzoate, Intragastric placebo, Intraduodenal quinine hydrochloride, Intraduodenal denatonium benzoate
- Keywords
- Bitter, Motilin, Ghrelin, CCK, GLP-1, SST, Denatonium benzoate, Quinine hydrochloride
- Medical subject headings
- Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intragastric quinine hydrochlorideDrug
Also called IG QHCl
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 benzoateDrug
Also called IG DB
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 placeboDrug
Also called IG PLC
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 hydrochlorideDrug
Also called ID QHCl
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 benzoateDrug
Also called IG DB
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 placeboDrug
Also called ID PLC
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.
| Study group | Role | What they receive |
|---|---|---|
| Intragastric quinine hydrochloride | Experimental | 10 µmol of quinine hydrochloride per kg body weight was administrated into the stomach. Receives: Drug: Intragastric quinine hydrochloride |
| intragastric denatonium benzoate | Experimental | 1 µmol of denatonium benzoate per kg body weight was administrated into the stomach. Receives: Drug: Intragastric denatonium benzoate |
| Intragastric placebo | Placebo comparator | 0.1 ml of water (placebo) per kg body weight was administrated into the stomach. Receives: Drug: Intragastric placebo |
| Intraduodenal quinine hydrochloride | Experimental | 10 µmol of quinine hydrochloride per kg body weight was administrated into the duodenum. Receives: Drug: Intraduodenal quinine hydrochloride |
| Intraduodenal denatonium benzoate | Experimental | 1 µmol of denatonium benzoate per kg body weight was administrated into the duodenum. Receives: Drug: Intraduodenal denatonium benzoate |
| Intraduodenal placebo | Placebo comparator | 0.1 ml of water (placebo) per kg body weight was administrated into the duodenum. Receives: Drug: Intraduodenal placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Infusion of bitter compounds into the stomach or duodenum is performed via a nasogastric feeding tube. Hunger is scored on a 100 mm visual analog scale at several time points during the experiment. Two hours after the infusion, the nasogastric feeding tube and intravenous dwelling line are removed and the subject drinks ad libitum from a chocolate milkshake until they are fully satisfied. Hunger is scored right before and after drinking the milkshake.
Measured: 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
Infusion of bitter compounds into the stomach or duodenum is performed via a nasogastric feeding tube. Two hours after the infusion of a bitter compound or placebo, the subjects drink ad libitum from a chocolate milkshake until they are fully satisfied. The milkshake is weighted before and after the experiment to calculate the amount of consumed calories (1 g milkshake = 1 kcal).
Measured: 2 hours after the infusion of a condition, subjects drink from the milkshake without an intermission.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jun 2019
- Study start2 Mar 2017
- Primary completion7 May 2018
- Study completion7 May 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for ObesityStudies of the same condition, open and under way.
- More trials run by Universitaire Ziekenhuizen KU LeuvenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Universitaire Ziekenhuizen KU Leuven
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jan Tack, Principal investigator, UZ Leuven
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03985865
- Sponsor's protocol ID
- S551166
- Acronym
- IG vs ID
- Status last verified
- Jan 2019
- First submitted
- 11 Jun 2019
- Last updated
- 14 Jun 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 34029163
Study at a glance
From the registry record, last updated by the sponsor on 14 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Influence of Bitter Substrates on Hunger, Gastrointestinal Hormone Release and Hedonic Food Intake
- ClinicalTrials.gov ID
- NCT03985865
- Acronym / sponsor ID
- IG vs ID / S551166
- Conditions
- Obesity
- Keywords
- Bitter, Motilin, Ghrelin, CCK, GLP-1, SST, Denatonium benzoate, Quinine hydrochloride
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Universitaire Ziekenhuizen KU LeuvenUniversity, hospital or other
- Study start
- 2 Mar 2017 (actual)
- Primary completion
- 7 May 2018 (actual)
- Study completion
- 7 May 2018 (actual)
- First posted
- 14 Jun 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Intragastric quinine hydrochloride | Experimental | Drug: Intragastric quinine hydrochloride10 µmol of quinine hydrochloride per kg body weight was administrated into the stomach. |
| intragastric denatonium benzoate | Experimental | Drug: Intragastric denatonium benzoate1 µmol of denatonium benzoate per kg body weight was administrated into the stomach. |
| Intragastric placebo | Placebo comparator | Drug: Intragastric placebo0.1 ml of water (placebo) per kg body weight was administrated into the stomach. |
| Intraduodenal quinine hydrochloride | Experimental | Drug: Intraduodenal quinine hydrochloride10 µmol of quinine hydrochloride per kg body weight was administrated into the duodenum. |
| Intraduodenal denatonium benzoate | Experimental | Drug: Intraduodenal denatonium benzoate1 µmol of denatonium benzoate per kg body weight was administrated into the duodenum. |
| Intraduodenal placebo | Placebo comparator | Drug: Intraduodenal placebo0.1 ml of water (placebo) per kg body weight was administrated into the duodenum. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (17 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Intragastric quinine hydrochlorideAlso: IG QHClA 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. | Drug | Intragastric quinine hydrochloride |
| Intragastric denatonium benzoateAlso: IG DBA 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. | Drug | intragastric denatonium benzoate |
| Intragastric placeboAlso: IG PLCA 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. | Drug | Intragastric placebo |
| Intraduodenal quinine hydrochlorideAlso: ID QHClA 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. | Drug | Intraduodenal quinine hydrochloride |
| Intraduodenal denatonium benzoateAlso: IG DBA 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. | Drug | Intraduodenal denatonium benzoate |
| Intraduodenal placeboAlso: ID PLCA 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. | Drug | Intraduodenal placebo |
Primary outcome
Changes in plasma levels of motilin, ghrelin, somatostatin, GLP-1 and CCK after bitter administration into the stomach or duodenum
Time frame: 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.
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.
2 secondary outcomes
Changes in hunger scores after bitter administration into the stomach or duodenum
Time frame: 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
Time frame: 2 hours after the infusion of a condition, subjects drink from the milkshake without an intermission.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jun 2019.
- Derived from this study: PubMed 34029163Verbeure 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jan Tack principal investigator
UZ Leuven
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Intragastric quinine hydrochloride, Intragastric denatonium benzoate and Intraduodenal quinine hydrochloride in people with Obesity, run by Universitaire Ziekenhuizen KU Leuven at 1 site in Belgium.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in plasma levels of motilin, ghrelin, somatostatin, GLP-1 and CCK after bitter administration into the stomach or duodenum (time frame: 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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03985865, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jun 2019.