Pre-diabetes
Conditions
Keywords
pre-diabetes, hydroxychloroquine, frequently sampled intravenous glucose tolerance testing, insulin resistance, insulin secretion, glucose tolerance
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.
Interventions
DRUGhydroxychloroquine
Thirteen weeks of oral hydroxychloroquine (400 mg/day) provided as capsules
OTHERPlacebo
Thirteen weeks of oral placebo provided as capsules
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
University of Pittsburgh
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Insulin Sensitivity | 13 weeks after baseline measurement | Change from baseline in the insulin sensitivity index (Si) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Beta Cell Function | 13 weeks after baseline measurement | Change from baseline in the disposition index (DI) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Hydroxychloroquine Hydroxychloroquine sulfate PO 400 mg daily | 17 |
| Placebo Placebo daily | 15 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Lost to Follow-up | 2 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Hydroxychloroquine | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 50.1 years STANDARD_DEVIATION 14.5 | 44.9 years STANDARD_DEVIATION 16.8 | 47.6 years STANDARD_DEVIATION 15.7 |
| Beta cell function (disposition index) | 1721 arbitrary units STANDARD_DEVIATION 2014 | 1214 arbitrary units STANDARD_DEVIATION 691 | 1483 arbitrary units STANDARD_DEVIATION 1540 |
| Insulin sensitivity (Si) | 0.52 10^-4 / pmol*l / min STANDARD_DEVIATION 0.27 | 0.58 10^-4 / pmol*l / min STANDARD_DEVIATION 0.42 | 0.55 10^-4 / pmol*l / min STANDARD_DEVIATION 0.34 |
| Sex: Female, Male Female | 15 Participants | 9 Participants | 24 Participants |
| Sex: Female, Male Male | 2 Participants | 6 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 3 / 17 | 3 / 15 |
| serious Total, serious adverse events | 0 / 17 | 0 / 15 |
Outcome results
Primary
Insulin Sensitivity
Change from baseline in the insulin sensitivity index (Si)
Time frame: 13 weeks after baseline measurement
Population: all randomized with last observation carried forward for missing data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Hydroxychloroquine | Insulin Sensitivity | 0.08 10^-4/pmol*l/min | Standard Error 0.03 |
| Placebo | Insulin Sensitivity | -0.11 10^-4/pmol*l/min | Standard Error 0.04 |
p-value: <0.01ANCOVA
Secondary
Beta Cell Function
Change from baseline in the disposition index (DI)
Time frame: 13 weeks after baseline measurement
Population: all randomized with last observation carried forward for missing data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Hydroxychloroquine | Beta Cell Function | 352 arbitrary units | Standard Error 143 |
| Placebo | Beta Cell Function | -218 arbitrary units | Standard Error 158 |
p-value: 0.013ANCOVA