Effects of Cinnamon Supplementation on Glucose Metabolism in Patients With Pre-diabetes
Condition: Dysglycemia; Obesity
Study type: Interventional
Phase: Phase 2

Summary: 
      The transition from normal glucose tolerance to overt type 2 diabetes mellitus (T2D)
      encompasses a variety of glycemic abnormalities that are commonly referred to as
      'prediabetes'. While intensive lifestyle interventions are the cornerstone of T2D prevention,
      developing safe, cost-effective adjunct therapeutic strategies is a clinically relevant goal.
      Cinnamon supplementation has been shown to improve fasting plasma glucose in patients with
      T2D. This placebo-controlled, randomized study will determine if cinnamon improves glucose
      homeostasis in patients with prediabetes over a 12-week period.
    

Detailed description: 
      BACKGROUND: The transition from normal glucose tolerance and insulin sensitivity to overt
      type 2 diabetes (T2D) encompasses a variety of glycemic abnormalities that are commonly
      referred to as 'prediabetes'. In 2003, 314 million people (8.2% of the adult population) had
      prediabetes, and this number is projected to increase to 472 million (9.0% of the adult
      population) by 2025. Approximately 40-50% of individuals with prediabetes have been reported
      to develop T2D within 10 years.

      While intensive lifestyle interventions remain the cornerstone of T2D prevention, targeted
      pharmacotherapy has been shown to be effective and may be considered in high-risk patients.
      Several antidiabetic medications prevent or, at least, delay the progression from prediabetes
      to diabetes, including metformin, α-glucosidase inhibitors or pioglitazone. However, cost,
      potential adverse effects, and secondary failure in the long-term have often limited the
      widespread use of these and other newer antidiabetic drugs in patients with prediabetes. For
      instance 10 to 20% of metformin-treated patients experience gastrointestinal side effects
      (nausea, vomiting, and diarrhea) leading to its discontinuation, whereas the use pioglitazone
      is often complicated by weight gain and increased risk of fractures.

      In this context, efficacious, cost-effective, and safe adjunct therapeutics for T2D
      prevention are highly desirable. The present trial proposes to test the effects of cinnamon
      in patients with prediabetes.

      RATIONALE: Several randomized controlled studies have addressed the effects of cinnamon on
      changes in glycated hemoglobin (HbA1c) and fasting plasma glucose (FPG) in adult patients
      with T2D. Almost all studies showed a significant 10-20% decrease in FPG from baseline and
      improvements in HbA1c, although the latter change often did not achieve statistical
      significance. These findings in patients with T2D provide the rational to test whether
      cinnamon exerts similar beneficial effects in patients with prediabetes.

      STUDY DESIGN: This is a multi-center placebo-controlled, randomized (1:1), double masked
      trail to assess the effects of cinnamon (cinnamomum burmannii) on glucose homeostasis over a
      12- week period. FPG, HbA1c, and other measures of glucose metabolism will be collected at
      baseline, after 6 weeks, and at the end of the 12-week study period. Participants will be
      prompted to report Adverse Events (AE) at the study visits or anytime during the study
      period.

      OUTCOMES: The primary outcome for the Cinnamon Trial is a change in the FPG level from
      baseline to week 12 of treatment, as compared to placebo. Secondary outcomes include change
      in the FPG from baseline to week 6 of treatment, and change from baseline in plasma glucose
      at 2 hours and area under the curve-glucose during a 75-gram oral glucose tolerance test to
      week 12. Data will be analyzed using the "intent-to-treat" approach, which includes all
      randomized subjects with at least one post-baseline FPG measurement; the supplementation
      group assignment will not be altered based on the subject's adherence to the regimen.

      SAMPLE SIZE DETERMINATION: Anticipating an absolute change in FPG smaller than what observed
      in previous studies in patients with T2D, 10 patients with prediabetes in total entering a
      two-treatment parallel-design study will provide 90% probability of detecting a true
      between-treatment difference in FPG means of 22 mg/dl with standard deviation of 10 mg/dl,
      using a paired two-sided comparison with type 1 error of 0.05. To allow for up to 20%
      dropout, 12 patients in total will be recruited.
    

Intervention name(s): Cinnamon; placebo
Intervention type(s): Dietary Supplement; Other
Intervention description(s): Cinnamon burmannii administered orally as 500-mg capsules three times a day over 12 weeks; Placebo administered orally as capsules three times a day over 12 weeks
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment