Clinical trial NCT01326533: Reducing Risk of Type 2 Diabetes: Hydroxychloroquine Use in Pre-Diabetes
Official title: Mechanisms of Action of Hydroxychloroquine in Reducing Risk of Type 2 Diabetes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Pre-diabetes
Keywords: pre-diabetes
hydroxychloroquine
frequently sampled intravenous glucose tolerance testing
insulin resistance
insulin secretion
glucose tolerance
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2011-03-31
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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

Primary outcomes:
measure: Insulin Sensitivity
timeFrame: 13 weeks after baseline measurement
Secondary outcomes:
measure: Beta Cell Function
timeFrame: 13 weeks after baseline measurement
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: University of Pittsburgh, Montefiore Hospital
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: Frederico Toledo, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.