Effects of Chromium on Insulin Resistance in Alzheimer Disease Patients

Study Overview
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Brief Summary
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The effect of Chromium to improve glucose levels in Alzheimer Disease (AD) is controversial. The hypothesis of the study is to evaluate the effect of supplementing the AD individuals with Chromium combined with exercise and assessing the effect of the supplementation on glucose metabolism.

Detailed Description
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Chromium is an essential nutrient required for optimal insulin activity and normal carbohydrate and lipid metabolism. Beyond its nutritional effects, dietary supplement of chromium causes beneficial outcomes against several diseases, in particular diabetes-associated complications such as Alzheimer Disease. Common forms include chromium chloride, chromium nicotinate, and chromium picolinate. The argument for chromium supplementation relies on evidence from case reports of resolution of diabetic symptoms refractory to insulin via chromium added to total parenteral nutrition, and experiments in which animals deficient in chromium exhibited impaired glucose metabolism. Chromium may influence glucose metabolism by increasing the number of insulin receptors or by binding insulin to receptors. The US Food and Drug Administration concludes that, based on recent studies, chromium picolinate may reduce the risk of insulin resistance and therefore may reduce the risk of type 2 diabetes. A number of systematic reviews and meta-analyses have been conducted to determine the effect of chromium on glycemic control, although large, quality trials are limited. The majority of studies have found no effect on measured outcomes, with a few studies contributing to the positive observed effects. Variations of preparations used in the trials and study conditions make generalization of the results difficult. In order to provide a comprehensive clinical evaluation of the effects of Chromium in AD patients, we will conduct a double-blinded and placebo-controlled trial in subjects with AD.

Official Title
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Effects of Chromium on Insulin Resistance in Alzheimer Disease Patients

Conditions
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Alzheimer Disease

Intervention / Treatment
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* Dietary Supplement: Chromium Chloride
* Other: Individual Exercise


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Outpatients with a diagnosis of Alzheimer's disease. Exhibiting an onset and progression of cognitive dysfunction during at least 3 months prior to the screening period. Exclusion Criteria: Patients with neurodegenerative diseases other than Alzheimer's disease. Patients with cognitive dysfunction due to cerebral damage resulting from a lack of oxygen, a brain injury, etc. Patients with clinically significant cardiovascular disease. Patients with history of clinically-evident stroke. Patients with history of cancer in the last 5 years. Patients with clinically-significant systemic illness that may affect safety or completion of the study.

Ages Eligible for Study
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Minimum Age: 65 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Chromium Chloride<br>Participants transdermal chromium chloride 50 to 600 mcg/day. | Dietary Supplement: Chromium Chloride<br>* Transdermal chromium chloride 50 to 600 mcg/day.<br>|
| Experimental: Individual Exercise<br>Exercise 150 minutes per week (over 3 to 5 days) for 12 weeks. | Other: Individual Exercise<br>* Participants will engage in 150 minutes of exercise over 3-5 days per week for 12 weeks<br>|
| No Intervention: Control Group<br>Participants or participant's caregiver will be provided educational materials on starting an exercise program and instructions for the application of transdermal chromium chloride, but will receive no formal support for their exercise program. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin Resistance | Insulin action will be determined by insulin clamp and OGTT using deuterated glucose both before and after treatment. | Change from Baseline to 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in chronic refractory mood disorders | To be measured using confirmatory factor analysis (CFA). CFA aggregates scores from across multiple subtests. | Change from Baseline to 12 weeks |