Rediscovering Hydroxychloroquine as a Novel Insulin Sensitizer

Study Overview
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Brief Summary
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Current options to treat insulin resistance in diabetes are fairly limited. For this reason, novel treatments would represent a major progress. The generic drug hydroxychloroquine (HCQ) has poorly understood effects on blood sugar metabolism. In this study, the investigators will examine the mechanisms by which this drug affects glucose metabolism and which cells are affected. Findings emanating from this project will help establish whether HCQ may be a viable treatment for disorders of glucose metabolism.

Official Title
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Rediscovering Hydroxychloroquine as a Novel Insulin Sensitizer

Conditions
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Insulin Resistance

Intervention / Treatment
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* Drug: Hydroxychloroquine
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 21-69 years-old; BMI 28-40; Presence of at least one of the following markers of insulin resistance: a) fasting hyperinsulinemia (>7 uU/ml by ultrasensitive insulin assay); impaired fasting glucose (100-125 mg/dl); prior history of impaired glucose tolerance provided by the participant; history of previous gestational diabetes; history of PCOS; waist circumference >40 (men) or >35 (women) (cut-offs from ATP-III criteria for metabolic syndrome). Exclusion Criteria: Pregnancy, or unable/unwilling to avoid pregnancy during the study; Unstable cardiopulmonary disease, hepatitis, liver dysfunction, renal insufficiency, or any other medical condition affecting glucose metabolism or safety during the study; Diabetes; Medications that affect glucose metabolism: (e.g. systemic glucocorticoids, antipsychotics); History of hypersensitivity to local lidocaine, similar anesthetics, or HCQ; History of G6PDH deficiency; History of retinopathy; Weight instability (>3Kg of weight change in the past three months); Bariatric surgery in the last two years, intention to lose weight or engage in exercise regimen during study; Alcohol intake >1 drink/day (averaged); Hemoglobin <10g%

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 69 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo PO | Other: Placebo<br>* Placebo PO for 13±1 weeks<br>|
| Experimental: Hydroxychloroquine<br>Hydroxychloroquine sulfate 400mg PO QD | Drug: Hydroxychloroquine<br>* Hydroxychloroquine sulfate 400mg/d PO for 13±1 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin sensitivity in muscle and liver |  | 13±1 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| biomarkers of inflammation |  | 13±1 weeks |