Effect of Zinc on Glucose Homeostasis

Study Overview
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Brief Summary
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The purpose of this investigation is to evaluate the impact of zinc supplementation on fasting glucose levels, hemoglobin A1c (HbA1c), and other indices of glucose homeostasis in individuals with prediabetes. The investigators hypothesize that prediabetic subjects receiving zinc will demonstrate a greater decrease in HbA1c and blood glucose compared to prediabetic subjects receiving placebo. Specific Aim: Conduct a prospective, double-blind randomized clinical trial comparing the effects of 12 months of zinc supplementation (zinc acetate 25 milligram [mg] per day) versus placebo on glucose homeostasis. Based upon expected effect size and power calculations, and anticipating a 20% drop-out rate, the investigators will study 200 prediabetic subjects (100 per group) using a 1:1 randomization design. HbA1c, fasting plasma glucose, and other measures will be obtained at 0, 6, and 12 months and will be compared between zinc supplementation and placebo groups.

Official Title
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Clinical and Nutrigenetic Assessment of Zinc in Participants With Prediabetes

Conditions
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Prediabetic State, Hyperglycemia

Intervention / Treatment
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* Drug: Zinc Acetate 25 MG
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Amish men or women who are 18 to 80 years old Prediabetes (HgbA1c = 5.7-6.4% or fasting glucose levels 100-125 mg/dL) Exclusion Criteria: Pregnant Currently breastfeeding History of severe gastrointestinal disorders or upper gastrointestinal surgery Has hemochromatosis, cancer, liver disease, kidney disease, cardiovascular disease, or other coexisting malignancy Hemoglobin < 12.5 g/dl (male) or < 11 g/dl (female) Severe hypertension (blood pressure > 160/95 mm Hg) Has a creatinine greater than 2.0 mg/dl, aspartate aminotransferase (AST) or alanine transaminase (ALT) greater than 2 times the upper limit of normal, hematocrit (Hct) less than 32%, or thyroid-stimulating hormone (TSH) less than 0.4 or greater than 5.5 milli-international units (mIU) per liter. At the discretion of the study physician or PI, taking medications that affect the outcomes of the study including, but not limited to, corticosteroids, anti-psychotic agents, protease inhibitors, oral contraceptives, estrogens, niacin, and some classes of antidepressants, statins, and antihypertensive medications Zinc hypersensitivity Use of denture adhesive containing zinc Taking other medications or zinc-containing supplements and is unwilling or cannot safely, in the opinion of the study physician, discontinue their use at least 2 weeks prior to protocol initiation Any other condition that would, in the opinion of the investigator, place them at an unacceptable risk or render them unable to meet the requirements of the protocol.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Two hundred prediabetic individuals will be enrolled. The investigators will prospectively evaluate the impact of zinc supplementation on fasting glucose levels and HbA1c, through the completion of randomized, placebo-controlled study of zinc acetate (one 25 mg tablet per day for 1 year) and placebo (1 tablet per day for 1 year). Participants will be randomized 1:1 to either zinc or placebo.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Zinc treatment<br>Research subjects administered zinc acetate for 1 year (one 25 mg tablet per day) | Drug: Zinc Acetate 25 MG<br>* Participants will take one tablet per day (25mg Zinc acetate [Galzin]) for 1 year<br>* Other names: Galzin 25 mg;|
| Placebo Comparator: Placebo<br>Research subjects administered placebo for 1 year (1 tablet per day) | Drug: Placebo<br>* Participants will take one placebo tablet per day for 1 year<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Zinc-dependent effect on fasting glucose levels at 1 year | One of the investigator's primary endpoints will be to determine the difference in fasting glucose levels between zinc-treated and placebo-treated individuals after 1 year of receiving study drug | 1 year | 
| Zinc-dependent effect on HbA1c at 1 year | One of the investigator's primary endpoints will be to determine the difference in HbA1c levels between zinc-treated and placebo-treated individuals after 1 year of receiving study drug | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Zinc-dependent effect on fasting glucose levels at 6 months | One of the investigator's secondary endpoints will be to determine the difference in fasting glucose levels between zinc-treated and placebo-treated individuals after 6 months of receiving study drug | 6 months | 
| Zinc-dependent effect on HbA1c at 6 months | One of the investigator's secondary endpoints will be to determine the difference Hba1c between zinc-treated and placebo-treated individuals after 6 months of receiving study drug | 6 months |