Reducing Risk of Type 2 Diabetes: Hydroxychloroquine Use in Pre-Diabetes

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine the short-term effects of the antimalarial medication, hydroxychloroquine (HCQ), compared with placebo using frequently sampled intravenous glucose tolerance testing (FSIGTT) methodology to study changes in insulin secretion and glucose tolerance in subjects at risk for developing Type 2 diabetes.

Detailed Description
-----------------
Diabetes is approaching epidemic proportions in the United States. This study evaluates the mechanisms of action of a generic drug that may have effects on glucose metabolism.

Official Title
-----------------
Mechanisms of Action of Hydroxychloroquine in Reducing Risk of Type 2 Diabetes

Conditions
-----------------
Pre-diabetes

Intervention / Treatment
-----------------
* Drug: hydroxychloroquine
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age > or = 18, able to provide informed consent Body-mass index greater than or equal to 25 Presence of at least one indicator of insulin resistance from the following list: Family history of Type 2 diabetes (parent, sibling) Fasting glucose 100 - 125 mg/dl Fasting serum insulin greater than or equal to 7uU/ml Personal history of gestational diabetes Negative pregnancy test for women with childbearing potential Exclusion Criteria: Diagnosis of diabetes mellitus Type 1 or Type 2 Active autoimmune disease, chronic infection, current malignancy (excluding basal cell carcinoma), or other active inflammatory state that, in the opinion of the investigators, would affect insulin sensitivity Oral corticosteroid use in prior six months, or expectation of needing corticosteroid therapy in upcoming six months Known allergy or intolerance to HCQ Known glucose-6 phosphate dehydrogenase deficiency Known eye disease associated with retinal pigmentation abnormalities Known diabetic retinopathy requiring past or planned laser therapy Inability to comply with visit schedule and protocol requirements Inability to manage and take medication as instructed Current or planned pregnancy in upcoming 12 months Inability or unwillingness to use reliable method of contraception (for women of childbearing years, men, or men's partners with childbearing potential), such as oral contraceptive pills, barrier method (diaphragm and condom with spermicide), intrauterine device, or depo-provera injections for 3 months prior to enrollment Anemia (HGB < 9) Any history of bariatric (weight loss) surgery Current use of the medication Glucophage (metformin) Weight changes of 6 pounds or more in the past 4 weeks Any other underlying or concomitant condition, which in the opinion of the principal investigator, could confound the results of the study or put the subject at undue risk

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: hydroxychloroquine<br>Thirteen weeks of daily hydroxychloroquine following FSIGTT testing | Drug: hydroxychloroquine<br>* Thirteen weeks of oral hydroxychloroquine (400 mg/day) provided as capsules<br>* Other names: Plaquenil;|
| Placebo Comparator: Placebo<br>Thirteen weeks of daily placebo following FSIGTT testing | Other: Placebo<br>* Thirteen weeks of oral placebo provided as capsules<br>* Other names: microcellulose placebo;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin Sensitivity | Change from baseline in the insulin sensitivity index (Si) | 13 weeks after baseline measurement | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Beta Cell Function | Change from baseline in the disposition index (DI) | 13 weeks after baseline measurement | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
pre-diabetes, hydroxychloroquine, frequently sampled intravenous glucose tolerance testing, insulin resistance, insulin secretion, glucose tolerance