To Determine the Effect of GLP1 on Cognitive Function, Brain Glucose Metabolism and Neuroplasticity.
Condition: Glucose Metabolism Disorders; Obesity; Degenerative Brain Disorder
MeSH terms: Brain Diseases; Metabolic Diseases; Glucose Metabolism Disorders
Study type: Interventional

Summary: 
      To test the hypothesis that GLP1 can exert favourable effects on multiple aspects of brain
      function. To this purpose, the investigator determine whether chronic increase in GLP1
      concentration as it occurs after bariatric surgery (Roux-en- Y Gastric Bypass) is associated
      with improvement in:

        -  cognitive function measured by Mini Mental State Examination (MMSE) and Mental
           Deterioration Battery(MDB).

        -  brain glucose metabolism measured by FDG-CT/PET

        -  neuroplasticity measure by binocular rivalry and saccadic adaptation tests in morbid
           obese subjects. In order to discern the effect of GLP1 irrespective of changes in the
           metabolic milieu the investigator will test whether short-term GLP-1 infusion can
           modulate the same parameters in healthy subjects.
    

Detailed description: 
      The research project will include two separate studies:

        1. In obese subjects undergoing RYGB to test the effect of chronic elevation of GLP1
           levels, and

        2. In normal volunteers to test the acute effect of GLP1, irrespective of changes in the
           metabolic milieu In several aspects of brain function as detailed below:.

      Morbid Obese Subjects Group:

      This study will consist in a single arm, non randomized, uncontrolled, single center
      before-and after RYGB in 15 morbid obese subjects.

      Healthy Subjects Group:

      This study will consist in a single arm, non randomized, uncontrolled, single center study in
      8 healthy subjects.

      The primary endpoint are the changes in:

        -  cognitive function measured by Mini Mental State Examination (MMSE) and Mental
           Deterioration Battery (MDB)

        -  brain glucose metabolism measured by FDG-CT/PET

        -  neuroplasticity measure by binocular rivalry and saccadic adaptation tests six months
           after RYGB in morbid obese subjects and with elevation of circulating GLP1 levels in
           healthy subjects.

      Morbid obese subjects participating in this study will be evaluated before and 6 months after
      bariatric surgery which is routinely performed to treat morbid obesity. For the purpose of
      baseline assessment subjects will undergo 3 visits at 1 week interval. All test procedures
      will be repeated in two subsequent visits 6 months after surgery with body weight being
      stable. Therefore, participation in the study will require a total of 5 visit with a
      post-trial phone contact 2 weeks after completion for safety assessment.

      Healthy subjects will be recruited for determining the acute effect of GLP1 on brain function
      irrespective of changes in the metabolic milieu. The study will require participation in a
      total of 3 visits.
    

Intervention name(s): RYGB; GLP-1
Intervention type(s): Procedure; Drug
Intervention description(s): RYGB is associated with a increase of circulating GLP-1 (up to ten-fold) especially in response to meal ingestion. This increased availability of GLP1 has been claimed to contribute to restoration of some of the beta-cell function.; GLP-1 is an hormone secreted by gut in response to nutrients ingestion.
Other intervention name(s): gut hormone
Intervention MeSH terms: Hormones
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: obesity; cognitive dysfunction