Safety and Tolerability Study of Cycloset in Treatment of Type 2 Diabetes
Condition: Type 2 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Study type: Interventional
Phase: Phase 3

Summary: 
      Cycloset, a new quick-release oral formulation of bromocriptine mesylate, effectively reduces
      blood sugar by the proposed mechanism of reversing many of the metabolic alterations
      associated with insulin resistance and obesity by resetting central (hypothalamic) circadian
      organization of monoamine neuronal activities.

      The primary analysis of this study will test the hypothesis that the rate of all-cause severe
      adverse events for those receiving usual drug therapy for diabetes management plus Cycloset
      is not greater than that for usual drug therapy plus placebo by more than an acceptable
      margin. While the primary purpose of this study is to establish the safety profile of
      Cycloset in type 2 diabetes, any potential positive cardiovascular benefits will be evaluated
      as well.
    

Detailed description: 
      Bromocriptine mesylate, an ergot derivative, is a sympatholytic dopamine D2 receptor agonist
      that can exert inhibitory effects on serotonin turnover in the central nervous system. It has
      been proposed that bromocriptine can reverse many of the metabolic alterations associated
      with insulin resistance and obesity by resetting central (hypothalamic) circadian
      organization of monoamine neuronal activities.

      While Cycloset has demonstrated efficacy by reducing HbA1c, fasting and post-prandial glucose
      and fasting and post-prandial triglycerides, the relatively small numbers of individuals
      treated for type 2 diabetes during the controlled Phase III clinical trials of Cycloset did
      not allow for a full evaluation of the safety profile. Since persons with diabetes are
      already at higher risk for cardiovascular disease, it is important to examine more fully the
      spectrum of potential adverse or positive effects from Cycloset in a large sample of persons
      with diabetes. Accordingly, the present study is designed to investigate the clinical safety
      of treatment with Cycloset in a broad population of persons with type 2 diabetes.

      To determine in subjects with type 2 diabetes mellitus receiving Usual Diabetes Therapy (UDT)
      consisting of either diet, oral hypoglycemic agents (OHA) (no more than 2), or insulin (with
      or without no more than 1 OHA) plus either Placebo or Cycloset:

        1. Whether add-on therapy with Cycloset results in all-cause rate of serious adverse
           events, which are not higher than add-on therapy with Placebo.

        2. Whether add-on therapy with Cycloset results in disease-specific rate of serious
           cardiovascular adverse events, which are not higher than add-on therapy with Placebo.

           While the primary purpose of this study is to establish the safety profile of Cycloset
           in type 2 diabetes, any potential positive cardiovascular benefits will be evaluated as
           well.

           Other clinical measures:

        3. The impact (either positive or negative) of Cycloset on HbA1c, fasting plasma glucose,
           weight, triglycerides lipids, blood pressure and patient tolerability after 12 months of
           therapy.

      Furthermore, Hba1c changes from baseline to 24 weeks between Cycloset and Placebo among
      subjects with a baseline Hba1c of >= 7.5% among the following subgroups:

      A. Treated at baseline with any Oral hypoglycemic agent (OHA) including injectable insulin
      secretagogues B. Metformin plus or minus one OHA or injectable insulin secretagogue C.
      Sulphonylurea plus or minus one OHA or injectable insulin secretagogue D. Treated at baseline
      with Metformin and one sulphonylurea
    

Intervention name(s): Cycloset; Usual Diabetes Therapy plus placebo
Intervention type(s): Drug; Drug
Intervention description(s): Usual diabetes therapy plus Cycloset; Placebo tablet taken orally once in the morning, beginning with one tablet daily, titrated up by 1 tablet each week to a maximum of 6 tablets daily
Other intervention name(s): bromocriptine mesylate; placebo
Intervention MeSH terms: Bromocriptine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: diabetes; diabetes mellitus