Bromocriptine-QR Therapy on Sympathetic Tone and Vascular Biology in Type 2 Diabetes Subjects
Condition: Diabetic Autonomic Neuropathy
MeSH terms: Diabetic Neuropathies
Study type: Interventional
Phase: Phase 4

Summary: 
      The main objective is to demonstrate the effects of early dopaminergic activation on the
      autonomic nervous system in subjects with newly diagnosed vs. established type 2 diabetes.
      The primary endpoint is the effect of Bromocriptine QR on changes in autonomic function
      measured by assessing sympathetic and parasympathetic function using conventional measures of
      autonomic function, including power spectral analysis of heart rate as well as peripheral
      autonomic function using sudorimetry and laser scanning of peripheral microvascular autonomic
      control.
    

Detailed description: 
      This is an interventional, twenty-four week, randomized, double blind, placebo-controlled
      trial with bromocriptine QR in subjects with newly diagnosed and established type 2 diabetes
      mellitus (T2DM) to evaluate its effects on the cardiovascular and peripheral autonomic
      nervous system, as well as on inflammatory markers, the leptin/adiponectin system, hormonal
      levels of RAS and HPA axis, indices of insulin resistance, and measures of oxidative and
      nitrosative stress. Forty newly diagnosed diabetes subjects and 40 subjects with established
      diabetes will be enrolled in the study and each randomized to treatment with bromocriptine-QR
      or placebo.

      Secondary endpoints will demonstrate the effects of dopaminergic activation with
      Bromocriptine-QR on the regulation of Hypothalamic-Pituitary-Axis (HPA) axis hormones, on the
      plasma levels of markers of inflammation and oxidative/nitrosative stress in newly diagnosed
      vs. established type 2 diabetes subjects. The study will evaluate treatment effects on
      inflammatory markers, the Leptin/Adiponectin system, and hormonal levels of
      rennin-angiotensin system (RAS), aldosterone and cortisol. Specifically, the following
      markers of inflammation and oxidative/nitrosative stress: 1) C reactive protein (CRP), 2)
      interleukin-6, 12, and 10, 3) tumor necrosis factor (TNFalpha), 4) plasminogen activator
      inhibitor (PAI1), superoxide dismutase (SOD), Thiobarbituric acid reactive substances (TBARS)
      and Asymmetric dimethylarginine (ADMA) will be evaluated. A co-secondary objective of the
      study will be to assess the impact of Bromocriptine-QR vs Placebo on measures of insulin
      resistance and glycemic control (e.g., oral glucose tolerance test (OGTT) glucose and
      insulin, Matsuda index, Homeostasis Model Assessment-insulin resistance (HOMA-IR), Hemoglobin
      A1c (HbA1c).
    

Intervention name(s): Cycloset; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Cycloset 1.6 -3.2 mg/day; Non-active placebo for cycloset
Other intervention name(s): Bromocriptine Mesylate Quick Release
Intervention MeSH terms: Bromocriptine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment