fMRI of Hypothalamic Responses to Taste, Temperature and Glucose (COLD-2)

Functional Magnetic Resonance Imaging of Human Hypothalamic Responses to Taste, Temperature and Glucose Sensing

The study will consist of five occasions with one week in between. BOLD signal intensity of the hypothalamus will be measured using fMRI. Measurements will be done before and after drinking 300 ml plain water or water to which glucose and/or ethyl butyrate will be added.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Other: Water; Other: Glucose; Other: Ethyl butyrate; Other: Glucose + ethyl butyrate; Other: Glucose + ethyl butyrate 0 C

Detailed Description

The hypothalamus is known to be important for control of feeding behaviour as well as the regulation of temperature. Functional magnetic resonance imaging (fMRI) is a non-invasive method, which detects transient haemodynamic changes in the brain, using blood oxygen level dependent (BOLD) signal differences.

In order to investigate the role of hypothalamic neural activity in response to taste, glucose and temperature, fMRI will be performed before, during and after ingestion of 300 ml plain water or water with added ethyl butyrate (pineapple flavour), added glucose or added ethyl butyrate plus glucose. All beverages will be consumed at 22 °C and the combination will also be drunk at 0 °C.

The study uses a randomised cross-over design in 16 healthy male subjects with a normal body weight. There will be an interval of at least one week between the five occasions.

BOLD signal intensity of the hypothalamus will be continuously measured for 21 minutes (5 minutes baseline, 4 minutes during drinking and 12 minutes after drinking).

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Zuid-Holland
    • Leiden, Zuid-Holland, Netherlands
      • Leids Universitair Medisch Centrum

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 25 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Signed informed consent
• Age between 18 and 25 years
• BMI between 20 and 23 kg/m2
• Length between 170 and 190 centimetres

Exclusion Criteria:

• Diabetes or history of other disturbances of glucose metabolism (eg impaired glucose tolerance, hypoglycaemia).
• Any genetic or psychiatric disease (e.g. fragile X syndrome, major depression) affecting brain
• Any significant chronic disease
• Renal or hepatic disease
• Recent weight changes or attempts to lose weight (> 3 kg weight gain or loss, within the last 3 months)
• Smoking (current or last 6 months)
• Alcohol consumption of more than 21 units per week or use of recreational drugs at present or in the last year
• Recent blood donation (within the last 2 months)
• Recent participation in other biomedical research projects (within the last 3 months), participation in 3 or more biomedical research projects in one year

• Contra-indication to MRI scanning:

  • Claustrophobia
  • Pacemakers and defibrillators
  • Nerve stimulators
  • Intracranial clips
  • Intraorbital or intraocular metallic fragments
  • Cochlear implants
  • Ferromagnetic implants

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

10

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Water/gluc/gluc+EB/EB/gluc+EB_cold; First Water 22 C, then Glucose 22 C, then Glucose + Ethyl butyrate 22 C, then Ethyl butyrate 22 C and then Glucose + Ethyl butyrate 0 C	Other: Water; Water, 300 ml, at room temperature; Other: Glucose; Water containing 50 g glucose, 300 ml, at room temperature; Other: Ethyl butyrate; Water containing ethyl butyrate (pineapple flavour) 300 ml, at room temperature; Other: Glucose + ethyl butyrate; Water containing 50 g glucose and ethyl butyrate (pineapple flavour) 300 ml, at room temperature; Other: Glucose + ethyl butyrate 0 C; Water containing 50 g glucose and ethyl butyrate (pineapple flavour) 300 ml, at 0 degrees centigrade
EXPERIMENTAL: Water/gluc+EB/gluc/gluc+EB_cold/EB; First Water 22 C, then Glucose + Ethyl butyrate 22 C, then Glucose 22 C, then Glucose + Ethyl butyrate 0 C and then Ethyl butyrate 22 C	Other: Water; Water, 300 ml, at room temperature; Other: Glucose; Water containing 50 g glucose, 300 ml, at room temperature; Other: Ethyl butyrate; Water containing ethyl butyrate (pineapple flavour) 300 ml, at room temperature; Other: Glucose + ethyl butyrate; Water containing 50 g glucose and ethyl butyrate (pineapple flavour) 300 ml, at room temperature; Other: Glucose + ethyl butyrate 0 C; Water containing 50 g glucose and ethyl butyrate (pineapple flavour) 300 ml, at 0 degrees centigrade
EXPERIMENTAL: Gluc/water/EB/gluc+EB/glucose+EB_cold; First Glucose 22 C, then Water 22 C, then Ethyl butyrate 22 C, then Glucose + Ethyl butyrate 22 C and then Glucose + Ethyl butyrate 0 C	Other: Water; Water, 300 ml, at room temperature; Other: Glucose; Water containing 50 g glucose, 300 ml, at room temperature; Other: Ethyl butyrate; Water containing ethyl butyrate (pineapple flavour) 300 ml, at room temperature; Other: Glucose + ethyl butyrate; Water containing 50 g glucose and ethyl butyrate (pineapple flavour) 300 ml, at room temperature; Other: Glucose + ethyl butyrate 0 C; Water containing 50 g glucose and ethyl butyrate (pineapple flavour) 300 ml, at 0 degrees centigrade
EXPERIMENTAL: Gluc/EB/water/gluc+EB_cold/gluc+EB; First Glucose 22 C, then Ethyl butyrate 22 C, then Water 22 C, then Glucose + Ethyl butyrate 0 C and then Glucose + Ethyl butyrate 22 C	Other: Water; Water, 300 ml, at room temperature; Other: Glucose; Water containing 50 g glucose, 300 ml, at room temperature; Other: Ethyl butyrate; Water containing ethyl butyrate (pineapple flavour) 300 ml, at room temperature; Other: Glucose + ethyl butyrate; Water containing 50 g glucose and ethyl butyrate (pineapple flavour) 300 ml, at room temperature; Other: Glucose + ethyl butyrate 0 C; Water containing 50 g glucose and ethyl butyrate (pineapple flavour) 300 ml, at 0 degrees centigrade
EXPERIMENTAL: EB/Gluc/gluc+EB_cold/water/glucose+EB; First Ethyl butyrate 22 C, then Glucose 22 C, then Glucose + Ethyl butyrate 0 C, then Water 22 C and then Glucose + Ethyl butyrate 22 C	Other: Water; Water, 300 ml, at room temperature; Other: Glucose; Water containing 50 g glucose, 300 ml, at room temperature; Other: Ethyl butyrate; Water containing ethyl butyrate (pineapple flavour) 300 ml, at room temperature; Other: Glucose + ethyl butyrate; Water containing 50 g glucose and ethyl butyrate (pineapple flavour) 300 ml, at room temperature; Other: Glucose + ethyl butyrate 0 C; Water containing 50 g glucose and ethyl butyrate (pineapple flavour) 300 ml, at 0 degrees centigrade
EXPERIMENTAL: EB/gluc+EB_cold/gluc/glucose+EB/water; First Ethyl butyrate 22 C, then Glucose + Ethyl butyrate 0 C, then Glucose 22 C, then Glucose + Ethyl butyrate 22 C and then Water 22 C	Other: Water; Water, 300 ml, at room temperature; Other: Glucose; Water containing 50 g glucose, 300 ml, at room temperature; Other: Ethyl butyrate; Water containing ethyl butyrate (pineapple flavour) 300 ml, at room temperature; Other: Glucose + ethyl butyrate; Water containing 50 g glucose and ethyl butyrate (pineapple flavour) 300 ml, at room temperature; Other: Glucose + ethyl butyrate 0 C; Water containing 50 g glucose and ethyl butyrate (pineapple flavour) 300 ml, at 0 degrees centigrade
EXPERIMENTAL: Gluc+EB_cold/water/glucose+EB/glucose/EB; First Glucose + Ethyl butyrate 22 C, then Water 22 C, then Glucose + Ethyl butyrate 0 C, then Glucose 22 C and then Ethyl butyrate 22 C	Other: Water; Water, 300 ml, at room temperature; Other: Glucose; Water containing 50 g glucose, 300 ml, at room temperature; Other: Ethyl butyrate; Water containing ethyl butyrate (pineapple flavour) 300 ml, at room temperature; Other: Glucose + ethyl butyrate; Water containing 50 g glucose and ethyl butyrate (pineapple flavour) 300 ml, at room temperature; Other: Glucose + ethyl butyrate 0 C; Water containing 50 g glucose and ethyl butyrate (pineapple flavour) 300 ml, at 0 degrees centigrade
EXPERIMENTAL: Gluc+EB_cold/glucose+EB/water/EB/glucose; First Glucose + Ethyl butyrate 22 C, then Glucose + Ethyl butyrate 0 C, then Water 22 C, then Ethyl butyrate 22 C and then Glucose 22 C	Other: Water; Water, 300 ml, at room temperature; Other: Glucose; Water containing 50 g glucose, 300 ml, at room temperature; Other: Ethyl butyrate; Water containing ethyl butyrate (pineapple flavour) 300 ml, at room temperature; Other: Glucose + ethyl butyrate; Water containing 50 g glucose and ethyl butyrate (pineapple flavour) 300 ml, at room temperature; Other: Glucose + ethyl butyrate 0 C; Water containing 50 g glucose and ethyl butyrate (pineapple flavour) 300 ml, at 0 degrees centigrade
EXPERIMENTAL: Gluc+EB_cold/gluc+EB/EB/water/glucose; First Glucose + Ethyl butyrate 0 C, then Glucose + Ethyl butyrate 22 C, then Ethyl butyrate 22 C, then Water 22 C and then Glucose 22 C	Other: Water; Water, 300 ml, at room temperature; Other: Glucose; Water containing 50 g glucose, 300 ml, at room temperature; Other: Ethyl butyrate; Water containing ethyl butyrate (pineapple flavour) 300 ml, at room temperature; Other: Glucose + ethyl butyrate; Water containing 50 g glucose and ethyl butyrate (pineapple flavour) 300 ml, at room temperature; Other: Glucose + ethyl butyrate 0 C; Water containing 50 g glucose and ethyl butyrate (pineapple flavour) 300 ml, at 0 degrees centigrade
EXPERIMENTAL: Gluc+EB_cold/EB/gluc+EB/glucose/water; First Glucose + Ethyl butyrate 0 C, then Ethyl butyrate 22 C, then Glucose + Ethyl butyrate 22 C, then Glucose 22 C and then Water 22 C	Other: Water; Water, 300 ml, at room temperature; Other: Glucose; Water containing 50 g glucose, 300 ml, at room temperature; Other: Ethyl butyrate; Water containing ethyl butyrate (pineapple flavour) 300 ml, at room temperature; Other: Glucose + ethyl butyrate; Water containing 50 g glucose and ethyl butyrate (pineapple flavour) 300 ml, at room temperature; Other: Glucose + ethyl butyrate 0 C; Water containing 50 g glucose and ethyl butyrate (pineapple flavour) 300 ml, at 0 degrees centigrade

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determine hypothalamic function in response to taste, temperature and glucose sensing	BOLD-signal intensity	Before (5 minutes) and after (12 minutes) drinking

Collaborators and Investigators

• Sponsor: Unilever R&D
• Collaborators: Leiden University Medical Center

Publications and helpful links

General Publications

• van Opstal AM, Hafkemeijer A, van den Berg-Huysmans AA, Hoeksma M, Blonk C, Pijl H, Rombouts SARB, van der Grond J. Brain activity and connectivity changes in response to glucose ingestion. Nutr Neurosci. 2020 Feb;23(2):110-117. doi: 10.1080/1028415X.2018.1477538. Epub 2018 May 27.

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 11, 2013
• Primary Completion (ACTUAL): October 30, 2014
• Study Completion (ACTUAL): October 30, 2014

Study Registration Dates

• First Submitted: June 26, 2017
• First Submitted That Met QC Criteria: June 26, 2017
• First Posted (ACTUAL): June 28, 2017

Study Record Updates

• Last Update Posted (ACTUAL): June 28, 2017
• Last Update Submitted That Met QC Criteria: June 26, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Other Study ID Numbers: 1302

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No