Functional Magnetic Resonance Imaging of Human Hypothalamic Responses to Oral Temperature and Glucose Sensing
Condition: Healthy
Study type: Interventional

Summary: 
      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.
    

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.
    

Intervention name(s): water 0; water 22; Glucose 0; Glucose 22
Intervention type(s): Other; Other; Other; Other
Intervention description(s): 300 ml tap water at 0 ºC; 300 ml tap water at 22 ºC; 300 ml tap water at 0 ºC with 75 grams of glucose added; 300 ml tap water at 22 ºC with 75 grams of glucose added
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Basic Science