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

Mechanisms of Action of Hydroxychloroquine in Reducing Risk of Type 2 Diabetes

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.

Study Overview

• Status: Completed
• Conditions: Pre-diabetes
• Intervention / Treatment: Drug: hydroxychloroquine; Other: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh, Montefiore Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age > or = 18, able to provide informed consent
2. Body-mass index greater than or equal to 25

3. 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
4. Negative pregnancy test for women with childbearing potential

Exclusion Criteria:

1. Diagnosis of diabetes mellitus Type 1 or Type 2
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
3. Oral corticosteroid use in prior six months, or expectation of needing corticosteroid therapy in upcoming six months
4. Known allergy or intolerance to HCQ
5. Known glucose-6 phosphate dehydrogenase deficiency
6. Known eye disease associated with retinal pigmentation abnormalities
7. Known diabetic retinopathy requiring past or planned laser therapy
8. Inability to comply with visit schedule and protocol requirements
9. Inability to manage and take medication as instructed
10. Current or planned pregnancy in upcoming 12 months
11. 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
12. Anemia (HGB < 9)
13. Any history of bariatric (weight loss) surgery
14. Current use of the medication Glucophage (metformin)
15. Weight changes of 6 pounds or more in the past 4 weeks
16. 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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: hydroxychloroquine; Thirteen weeks of daily hydroxychloroquine following FSIGTT testing	Drug: hydroxychloroquine; Thirteen weeks of oral hydroxychloroquine (400 mg/day) provided as capsules; Other Names: Plaquenil
Placebo Comparator: Placebo; Thirteen weeks of daily placebo following FSIGTT testing	Other: Placebo; Thirteen weeks of oral placebo provided as capsules; 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

Collaborators and Investigators

• Sponsor: University of Pittsburgh
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Principal Investigator: Frederico Toledo, MD, University of Pittsburgh

Publications and helpful links

General Publications

• Wasko MC, McClure CK, Kelsey SF, Huber K, Orchard T, Toledo FG. Antidiabetogenic effects of hydroxychloroquine on insulin sensitivity and beta cell function: a randomised trial. Diabetologia. 2015 Oct;58(10):2336-43. doi: 10.1007/s00125-015-3689-2. Epub 2015 Jul 22.

Study record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (Actual): March 1, 2013
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: March 29, 2011
• First Submitted That Met QC Criteria: March 29, 2011
• First Posted (Estimate): March 31, 2011

Study Record Updates

• Last Update Posted (Estimate): February 26, 2016
• Last Update Submitted That Met QC Criteria: January 28, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Keywords: insulin resistance; hydroxychloroquine; insulin secretion; glucose tolerance; pre-diabetes; frequently sampled intravenous glucose tolerance testing
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Hyperglycemia; Diabetes Mellitus; Prediabetic State; Glucose Intolerance; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Hydroxychloroquine
• Other Study ID Numbers: DK082878; 5R21DK082878-02 (U.S. NIH Grant/Contract)