Examination of Bromocriptine on Homeostatic and Hedonic Mechanisms of Food Intake in Individuals at High Risk for T2DM
Condition: Overweight and Obesity; Eating Behavior
MeSH terms: Overweight
Study type: Interventional
Phase: Phase 3

Summary: 
      The current project applies an integrative three-prong approach to investigate the potential
      of the dopamine D2 receptor (DRD2) agonist bromocriptine to: 1) increase homeostatic
      satiation signaling, 2) alter neural circuitry to reduce hedonically motivated food intake,
      and 3) examines a genetic predisposition that may markedly impact the effectiveness of this
      medication in those at high risk for T2DM.
    

Detailed description: 
      Twenty-nine million Americans have diagnosed type 2 diabetes (T2DM), with fewer than half
      able to meet treatment goals and considerably more are at risk for development of T2DM.
      Implementation of healthy eating behavior has been identified as a barrier to T2DM treatment
      and efficacy. The determinants of eating behavior and weight regulation involve a complex
      interaction among individual-level homeostatic, hedonic, and genetic systems, and the
      external food environment. The high prevalence of obesity and T2DM suggests hedonic
      motivation to consume food overrides homeostatic satiation signaling, resulting in excess
      food intake. Elevated intake increases body mass and promotes T2DM incidence via
      dysregulation of glucagon-like peptide 1 (GLP-1), amylin, and adiponectin, which in turn can
      negatively impact T2DM treatment options.

      Use of a pharmaceutical, such as bromocriptine, to aid in behavioral change is a novel method
      for treating and ameliorating T2DM and warrants investigation given that previous work has
      shown reward response to food images mediates T2DM control. Use of functional magnetic
      resonance imaging (fMRI) techniques to predict and evaluate hedonically-motivated eating
      behavior can be used to measure sensitivity to reward, and the role it plays in developing
      obesity, and is therefore an excellent tool to examine the associations among bromocriptine,
      satiety hormones, reward sensitivity and eating behavior.

      Moreover, since 20-35% of the population carries the DRD2 TaqIA A1 allele, and 65% of the
      population is overweight or obese and at high risk for T2DM development or currently
      diagnosed, as much as 23% of the population may greatly benefit from dopamine agonist
      treatment. Despite the possibility that bromocriptine may have robust impact on T2DM
      treatment or as prevention therapy in those that are genetically predisposed, few data are
      available that directly examine the three systems (homeostatic, hedonic, genetic) available
      to assess whether a genetically-informed, personalized T2DM treatment is viable.
    

Intervention name(s): Placebo; Bromocriptine-QR
Intervention type(s): Drug; Drug
Intervention description(s): 2 capsules, orally administered once; 1.6mg (2 0.8mg capsules), orally administered once
Other intervention name(s): placebo (calcium supplement); quick-release (QR) bromocriptine (cycloset)
Intervention MeSH terms: Bromocriptine
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Participants are randomly assigned to one of two possible intervention arms (active drug vs. placebo) at baseline. Following a 2-week washout period, participants receive the other intervention.
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Diagnostic
Keywords: bromocriptine; dopamine agonist; TaqIA polymorphism; eating behavior; food intake; overweight; obesity