Functional Magnetic Resonance Imaging of Human Hypothalamic Responses to Oral Temperature and Glucose Sensing (COLD)

The study will consist of four occasions with one week between the occasions. fMRI will be performed to monitor hypothalamic activity before and after an ingestion of 1 of the following 4 stimuli (300 ml of each): water at room temperature, water at 0 degrees Celsius, glucose solution at room temperature, glucose solution at 0 degrees Celsius. The last two stimuli both contain 75 gram glucose. The order of conditions will be randomly assigned to the subjects. Functional connectivity of the hypothalamic regions will be assessed by analysing the resting state fMRI.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Other: water 0; Other: water 22; Other: Glucose 0; Other: Glucose 22

Detailed Description

Background of the study: Thermo-regulation is an important aspect of human homeostasis. A decrease in brain and/or body temperature will increase energy requirements and eventually food intake, which acts as a defence against hypothermia. The hypothalamus plays a central role in the regulation of temperature as well as in the control of energy intake, feeding behaviour and lipid and glucose metabolism. The effect of both cooling and changes in energy demand, will therefore be reflected in hypothalamic activity.

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 response to external or internal stimuli. Recently, several fMRI studies have shown the feasibility of measuring hypothalamic function in response to glucose ingestion.

In order to investigate the role of hypothalamic neural activity in response to cooling by food temperature and the additional effect of glucose concentration, fMRI will be performed in healthy men after ingestion of one of 4 solutions at different temperatures and with different glucose concentration.

The study will consist of four occasions. There will be an interval of at least one week between the occasions. On all occasions, the subject will be admitted to the Clinical Research Unit of the LUMC. After a acclimatisation period of 30 minutes and anthropometric measurements (weight and height), fMRI to monitor hypothalamic activity will be performed after an ingestion of 1 of the following 4 stimuli (300 ml of each): water at room temperature, water almost frozen (0 C), glucose solution at room temperature, almost frozen glucose solution (0 C). The last two stimuli both contain 75 gram glucose. Conditions will be randomly assigned to the subjects, a batch wise randomisation procedure will be followed. The order of allocation of each subject is recorded on paper and stored in a sealed envelop, which will be opened after inclusion in the study. The hypothalamus will be continuously imaged for 20 min. (8 min baseline, 4 min drinking, 8 min post ingestion) using a conventional T2*-weighted gradient-echo pulse sequence. A resting state fMRI will be carried out before and after the fMRI of the hypothalamic activity. Hedonic changes or reward effects of the administration will be captured by separate analysis of the amygdala and nucleus accumbens in each subject.

• 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: No
• 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 loose 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 2 or more biomedical research projects in one year

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: water 22, water 0, glucose 0, glucose 22; Subjects consume 300 ml water at 22 ºC, 300 ml water at 0 ºC, 300 ml water at 0 ºC containing 75 grams glucose and 300 ml water at 22 ºC containing 75 grams glucose sequentially with a one-week washout between consumptions	Other: water 0; 300 ml tap water at 0 ºC; Other: water 22; 300 ml tap water at 22 ºC; Other: Glucose 0; 300 ml tap water at 0 ºC with 75 grams of glucose added; Other: Glucose 22; 300 ml tap water at 22 ºC with 75 grams of glucose added
Experimental: water 0, glucose 22, water 22, glucose 0; Subjects consume 300 ml water at 0 ºC, 300 ml water at 22 ºC containing 75 grams glucose, 300 ml water at 22 ºC and 300 ml water at 0 ºC containing 75 grams glucose sequentially with a one-week washout between consumptions	Other: water 0; 300 ml tap water at 0 ºC; Other: water 22; 300 ml tap water at 22 ºC; Other: Glucose 0; 300 ml tap water at 0 ºC with 75 grams of glucose added; Other: Glucose 22; 300 ml tap water at 22 ºC with 75 grams of glucose added
Experimental: glucose 22, glucose 0, water 0, water 22; Subjects consume 300 ml water at 22ºC containing 75 grams glucose, 300 ml water at 0 ºC containing 75 grams glucose, 300 ml water at 0 ºC and 300 ml water at 22 ºC sequentially with a one-week washout between consumptions	Other: water 0; 300 ml tap water at 0 ºC; Other: water 22; 300 ml tap water at 22 ºC; Other: Glucose 0; 300 ml tap water at 0 ºC with 75 grams of glucose added; Other: Glucose 22; 300 ml tap water at 22 ºC with 75 grams of glucose added
Experimental: glucose 0, water 22, glucose 22, water 0; Subjects consume 300 ml water at 0 ºC containing 75 grams glucose, 300 ml water at 22 ºC, 300 ml water at 22 ºC containing 75 grams glucose and 300 ml water at 0 ºC sequentially with a one-week washout between consumptions	Other: water 0; 300 ml tap water at 0 ºC; Other: water 22; 300 ml tap water at 22 ºC; Other: Glucose 0; 300 ml tap water at 0 ºC with 75 grams of glucose added; Other: Glucose 22; 300 ml tap water at 22 ºC with 75 grams of glucose added

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Functional magnetic resonance imaging of the hypothalamus	Hypothalamic neural activity measured using Blood Oxygen Level Dependent signal measured by functional magnetic resonance imaging	fMRI measurements between 8 and 20 minutes after start of beverage intake

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Functional magnetic resonance imaging of the amygdala	Neural activity in the amygdala measured using Blood Oxygen Level Dependent signal	fMRI measurements between 8 and 20 minutes after start of beverage intake
Functional magnetic resonance imaging of the nucleus accumbens	Neural activity in the nucleus accumbens measured using Blood Oxygen Level Dependent signal	fMRI measurements between 8 and 20 minutes after start of beverage intake

Collaborators and Investigators

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

Publications and helpful links

General Publications

• van Opstal AM, van den Berg-Huysmans AA, Hoeksma M, Blonk C, Pijl H, Rombouts SARB, van der Grond J. The effect of consumption temperature on the homeostatic and hedonic responses to glucose ingestion in the hypothalamus and the reward system. Am J Clin Nutr. 2018 Jan 1;107(1):20-25. doi: 10.1093/ajcn/nqx023.

Study record dates

Study Major Dates

• Study Start (Actual): January 28, 2013
• Primary Completion (Actual): May 23, 2013
• Study Completion (Actual): May 23, 2013

Study Registration Dates

• First Submitted: June 6, 2017
• First Submitted That Met QC Criteria: June 6, 2017
• First Posted (Actual): June 8, 2017

Study Record Updates

• Last Update Posted (Actual): June 9, 2017
• Last Update Submitted That Met QC Criteria: June 8, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Other Study ID Numbers: FDS-BNH-0770

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