Effects of Intragastric Quinine, Alone or Combined With L-leucine, on Postprandial Glycaemic Control

NCT05720390 | Completed

• 1 other identifier: R20161005-1
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

In this study, participants will receive, in a randomized, double-blind fashion, an intragastric bolus administration of either (i) 300 mg quinine, (ii) 5 g L-leucine, (iii) a combination of (i)+(ii), or (iv) control, before 350 ml (500 kcal) of a mixed-nutrient drink, to evaluate the effects on postprandial blood glucose, gastric emptying, and the hormone responses to the mixed-nutrient drink. Study visits will be separated by 3-7 days and participants will receive one treatment per visit. On each study visit, the participant will be intubated with a nasogastric feeding tube. At t= - 60 min (08:30 am), a baseline blood sample, visual analogue scale questionnaire (VAS), and breath sample will be collected and quinine or control will be administered through the feeding tube. 30 min later (at t= - 30 min), L-leucine or control will be administered over 2 min after which the feeding tube will be removed immediately. At t = -45, -30, -15, and -1 min further blood samples will be collected and VAS completed. At t = -1 min, participants will consume, within 1 minute, a mixed-nutrient drink, labelled with 100 mg of 1-13C-acetate for measurement of gastric emptying by breath sampling. Blood samples, VAS, and breath samples will be taken at regular intervals between t = 0-180 min.

Conditions

Healthy

Keywords

Intragastric; Quinine; L-leucine; Glycaemic control; Plasma glucose; Glucoregulatory hormones; Gastric emptying; Humans

Outcome Measures

Primary Outcomes (1)

• Change from baseline plasma glucose concentration after a mixed-nutrient drink for 3 hours

  Plasma glucose concentrations (mmol/L) will be assessed using glucose oxidase method

  Blood samples will be taken repeatedly within each study visit (i.e. at baseline (t= 0 minute), after administration of study treatments (t= -45, -30, -15 minutes) and after a mixed-nutrient drink (t= 0, 15, 30, 45, 60, 90, 120 and 180 minutes).

Secondary Outcomes (4)

• Gastric emptying of a mixed nutrient drink

  Breath samples will be taken repeatedly on each study visit (i.e. t= 0 (baseline), 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 75, 90, 105,120, 135, 150, 165, 180 minutes) to construct a gastric emptying profile on each day.

• Plasma concentration of insulin after a mixed-nutrient drink

  Blood samples will be taken repeatedly within each study visit (i.e. at baseline (t= 0 minute), after administration of study treatments (t= -45, -30, -15 minutes) and after a mixed-nutrient drink (t= 0, 15, 30, 45, 60, 90, 120 and 180 minutes).

• Plasma concentration of glucagon after a mixed-nutrient drink

  Blood samples will be taken repeatedly within each study visit (i.e. at baseline (t= 0 minute), after administration of study treatments (t= -45, -30, -15 minutes) and after a mixed-nutrient drink (t= 0, 15, 30, 45, 60, 90, 120 and 180 minutes).

• Gastrointestinal symptoms (nausea and bloating)

  Visual Analogue ratings will be collected repeatedly within each study visit (i.e. at baseline (t = 0 minute), after administration of treatments (t= -45, -30, -15 minutes) and after mixed-nutrient drink (t= 0, 15, 30, 45, 60, 90, 120 and 180 minutes).

Study Arms (4)

Quinine only

ACTIVE COMPARATOR

In this arm, participants will receive a 10 ml intragastric bolus of 300 mg quinine followed 30 min later by 100 ml intragastric bolus of control for L-leucine.

Other: Quinine; Other: Control

L-leucine only

ACTIVE COMPARATOR

In this arm, participants will receive a 10 ml intragastric bolus of control for quinine followed 30 min later by 100 ml intragastric bolus of 5 g L-leucine.

Other: L-leucine; Other: Control

Quinine + L-leucine

ACTIVE COMPARATOR

In this arm participants will receive a 10 ml intragastric bolus of 300 mg quinine followed 30 min later by 100 ml intragastric bolus of 5 g L-leucine.

Other: Combination of quinine and L-leucine

Control

PLACEBO COMPARATOR

In this arm, participants will receive a 10 ml intragastric bolus of control solution followed 30 min later by 100 ml intragastric bolus of control solution.

Other: Control

Interventions

Quinine OTHER

Quinine, which is a bitter compound, extracted from the bark of the cinchona tree and has been shown in our previous studies to lower blood glucose in doses of 300-600 mg, will be 'active' in this condition.

Quinine only

L-leucine OTHER

L-leucine, which is a branched-chain amino acid, and one of the building blocks of protein, therefore is part of our daily diet, will be 'active' in this condition.

L-leucine only

Combination of quinine and L-leucine OTHER

In this condition, both quinine and L-leucine will be administered as 'active'.

Quinine + L-leucine

Control OTHER

In the condition, where quinine is 'active', control for L-leucine (5 ml oraplus and 95 ml saline) will be administered. In the condition, where L-leucine will be 'active', control for quinine (10 ml distilled water) will be administered.

Control; L-leucine only; Quinine only

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Lean weight (BMI 19-25 kg/m2)

You may not qualify if:

• Significant gastrointestinal symptoms, disease or surgery;
• Current gallbladder or pancreatic disease;
• Cardiovascular or respiratory diseases;
• Any other illnesses as assessed by the investigator (including chronic illnesses not explicitly listed above);
• Use of prescribed or non-prescribed medications (including vitamins and herbal supplements) which may affect energy metabolism, gastrointestinal function, bodyweight or appetite (eg domperidone and cisapride, anticholinergic drugs (eg atropine), metoclopramide, erythromycin, hyoscine, orlistat, green tea extracts, Astragalus, St Johns Wort etc.);
• Individuals with low ferritin levels (less than 30 ng/mL), or who have donated blood in the 12 weeks prior to taking part in the study;
• Lactose intolerance/other food allergy(ies);
• Vegetarians;
• Restrained eaters (score \>12 on the three-factor eating questionnaire);
• Current intake of greater than 2 standard drinks on greater than 5 days per week;
• Current smokers of cigarettes/cigars/marijuana;
• Current intake of any illicit substance;
• High performance athletes;
• Inability to comprehend study protocol;
• Unable to tolerate naso-gastric tube

Sponsors & Collaborators

• University of Adelaide: lead

Study Sites (1)

Clinical Research Facility, Adelaide Health and Medical Sciences Building

Adelaide, South Australia, 5005, Australia

Location

Related Publications (1)

• Sajjad M, Ghorbaninejad P, Bitarafan V, Anjom-Shoae J, Rose BD, Fitzgerald PC, Horowitz M, Feinle-Bisset C. Effects of Combined Intragastric Administration of Quinine with L-Leucine or L-Isoleucine on the Glycemic Response to, and Gastric Emptying of, a Mixed-Nutrient Drink in Healthy Males. J Nutr. 2025 Dec 7:101259. doi: 10.1016/j.tjnut.2025.101259. Online ahead of print.

  PMID: 41365468 DERIVED

MeSH Terms

Interventions

Quinine; Leucine

Intervention Hierarchy (Ancestors)

Cinchona Alkaloids; Alkaloids; Heterocyclic Compounds; Quinuclidines; Heterocyclic Compounds, Bridged-Ring; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Amino Acids, Branched-Chain; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Essential

Study Officials

• Christine Feinle-Bisset, PhD

  University of Adelaide, Adelaide, South Australia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: In order to blind both investigator and participant, the treatments will be prepared on the morning of each study day, and filled in covered syringes, by a research officer who will have no involvement in data analysis.
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 31, 2023
• First Posted: February 9, 2023
• Study Start: February 2, 2023
• Primary Completion: April 9, 2024
• Study Completion: April 9, 2024
• Last Updated: December 10, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)