A Double-Blind, Placebo-Controlled Trial of Anti-Aging, Pro-Autophagy Effects of Metformin in Adults With Prediabetes
Condition: PreDiabetes; Aging
MeSH terms: Prediabetic State; Glucose Intolerance
Intervention: Metformin; Placebo Oral Tablet
Intervention description: Total daily dose titrated up to 1500 mg po q day over the course of 4 weeks and continued for a total exposure of 12 weeks.; Total daily dose titrated up to 1944 mg po q day over the course of 4 weeks and continued for a total exposure of 12 weeks.
Intervention MeSH terms: Metformin; Calcium Carbonate
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: This is a double-blind, approximate placebo-controlled trial of 12 weeks of metformin vs. CaCO3 (Placebo) among adult patients with prediabetes.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking description: Only the study research pharmacy will have access to the randomization list.
Enrollment: 25.0
Sex: All
Minimum age: 30 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: Autophagy

Summary:

      The goal of this pilot and feasibility study is to investigate the effects of a short course
      of metformin therapy on a surrogate marker of cellular senescence and autophagy among adult
      patients with prediabetes. The overall hypothesis is that metformin will have beneficial
      effects on longevity and quality of life by inducing autophagy downstream of activating
      adenosine monophosphate-activated protein kinase (AMPK) and inhibiting mechanistic target of
      rapamycin (mTOR) through potential effects of reduced inflammation, reduced degeneration of
      muscle and tendon tissue, antineoplastic effects, reduced obesity and hyperglycemia,
      preserved cardiovascular functions, and/or the prevention of neurodegeneration (such as
      age-associated dementia). This pilot study will address the following aim:

      Demonstrate that metformin therapy will increase cellular autophagy as an inverse correlate
      of aging as measured by increases in Microtubule-associated protein 1A/1B-light chain 3 (LC3)
      scores.

      Hypothesis 1: In addition to beneficial effects on glycemia, body weight, and body
      composition, metformin therapy exerts beneficial effects on surrogate measures of autophagy
      and aging.

      Primary outcome: Increased levels of LC3 in leukocytes.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Adults with prediabetes (defined as an A1c of 5.7-6.4%)

          -  BMI between 27 and 40 kg/m2 (inclusive).

        Exclusion Criteria:

          -  Prior treatment with metformin or other diabetes medications,

          -  Pregnancy,

          -  Significant renal dysfunction (Serum Creatinine > 1.3 mg/dl for women, > 1.4 mg/dl for
             men),

          -  Severe hepatic dysfunction (aspartate amnotransferease [AST] or alanine
             aminotransferase [ALT] > 3 times the upper limit of normal),

          -  Ongoing alcohol or substance abuse,

          -  Inflammatory bowel disease,

          -  Ongoing glucocorticoid therapy,

          -  Or inability to render informed consent.