Bromocriptine-QR Therapy on Sympathetic Tone and Vascular Biology in Type 2 Diabetes Subjects
Condition: Diabetic Autonomic Neuropathy
MeSH terms: Diabetic Neuropathies
Intervention: Cycloset; Placebo
Intervention description: Cycloset 1.6 -3.2 mg/day; Non-active placebo for cycloset
Intervention MeSH terms: Bromocriptine
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 84.0
Sex: All
Minimum age: 30 Years
Maximum age: 80 Years
Healthy volunteers: No

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Type 2 diabetes subjects between the ages of 30 and 80 years of age, inclusive, at
             Screening

          -  Hemoglobin A1c (HbA1c) ≤10.0% at screening

          -  Male or female (female of child bearing age must use definitive contraceptive therapy)

          -  Type 2 Diabetes Mellitus subjects on a stable anti-diabetes regimen of diet and/or
             metformin alone therapy or on metformin plus an insulin secretion enhancer
             (sulfonylureas, dipeptidyl peptidase 4 (DPP4) Inhibitors, Glucagon-like peptide
             (GLP-1) analogs) therapy for a 60 day period prior to randomization. Subjects with
             diabetes duration of ≥ 4 years must be using an insulin secretion enhancer (e.g.
             sulphonylureas (SU), DPP4, GLP-1 analog). Subjects must have a documented C-peptide
             level (either fasting or random) of >2 ng/ml from the screening visit.

        Exclusion Criteria:

          -  Presence of type 1 diabetes mellitus (defined as C-peptide <1 ng /ml)

          -  Type 2 diabetes mellitus subjects on insulin.

          -  Use of prescription sympathomimetics, ergot alkaloid derivatives, or anti-migraine
             medications, dopamine2 (D2)-like receptor antagonists (e.g. metoclopramide,
             domperidone) or systemic corticosteroids

          -  Uncontrolled hypertension (systolic BP >160 or diastolic BP > 100 at screening) or a
             history of orthostatic hypotension

          -  History of significant gastroparesis

          -  Presence of diabetic retinopathy that is more severe than "background" level

          -  Presence of diabetic nephropathy, or renal impairment defined by blood urea nitrogen
             (BUN) >40mg/dl and serum creatinine > 1.4 mg/dl if female taking metformin, >1.5
             mg/dl. if male taking metformin, and >1.6 mg/dl if not taking metformin

          -  Presence of clinically significant peripheral or autonomic neuropathy that is clearly
             of non-diabetic origin

          -  History of major macrovascular events such as myocardial infarction or cerebrovascular
             event such as stroke within the past 6 months. Other exclusions include coronary
             artery bypass graft or coronary angioplasty in the previous 3 months, unstable angina
             pectoris (chest pain at rest, worsening chest pain, or admission to the emergency room
             or hospital for chest pain) within the previous 3 months, or seizure disorders.

          -  Active infection (e.g., human immunodeficiency virus (HIV), hepatitis), or a history
             of severe infection during the 30 days prior to screening

          -  Major surgical operation during the 30 days prior to screening

          -  Cancer, other than non-melanoma skin or non-metastatic prostate cancer, within the
             past 5 years

          -  Uncontrolled or untreated hypothyroidism as evidenced by thyroid stimulating hormone
             (TSH) concentrations >4.8 µU/ml

          -  Other serious medical conditions which, in the opinion of the investigator, would
             compromise the subject's participation in the study, including any concurrent illness,
             other than diabetes mellitus, not controlled by a stable therapeutic regimen, or
             conditions or abnormalities (e.g., blindness) that might interfere with interpretation
             of safety or efficacy data, or history of non-compliance

          -  Clinically significant abnormalities on screening laboratory evaluation, unless
             approved by the Sponsor

          -  Abnormalities of liver function defined as any liver enzymes (aspartate
             aminotransferase (AST), alanine aminotransferase (ALT), serum glutamic-pyruvic
             transaminase (SGPT), Serum glutamic oxaloacetic transaminase (SGOT) greater than 3
             times the upper limit of normal

          -  History of New York Heart Association (NYHA) Class III-IV congestive heart failure.

          -  Concurrent participation in another clinical trial with use of an experimental drug or
             device within 30 days of study entry.

          -  History of alcohol or substance abuse or dementia

          -  Pregnant or lactating women. Women of childbearing potential must have a negative
             pregnancy test at screening. Women who become pregnant will be discontinued from the
             study.

          -  Known hypersensitivity to any of the formulation components

          -  Working rotating, varying or night shifts

          -  Use of unapproved herbal supplements that may be associated with a risk of
             cardiovascular events (such as ephedra, yohimbe etc)

          -  Patients who have started therapy with an erectile dysfunction drug within 2 weeks
             prior to screening; patients may not begin treatment with an erectile dysfunction drug
             during the study period; patients currently taking erectile dysfunction drugs should
             do so only under medical supervision.

          -  Donation of blood in the previous 30 days. Blood donation is also not allowed during
             the study or for 30 days after completion of the study.