Type 2 Diabetes Mellitus
Conditions
Keywords
Type 2 Diabetes, Overweight
Brief summary
The basic plan of the study is to randomize otherwise healthy subjects with type 2 diabetes to hydroxychloroquine, 200 mg twice daily or placebo.
Detailed description
Hydroxychloroquine is a medicine that has been used for a long time to treat patients with malaria, rheumatoid arthritis, lupus and other conditions. It is closely related to chloroquine but with a better side effect profile for long term use. In treating these conditions it was discovered to have some beneficial properties like lowering cholesterol and lowering sugar in the blood of those who have diabetes. The mechanisms underlying these effects are unknown. In animal studies, we have discovered that chloroquine appears to decrease glucose, lower blood pressure and decrease atherosclerosis (hardening of the arteries). This collection of problems commonly occurs in the metabolic syndrome and diabetes mellitus, which affects over 20% and 7% of adults in Western countries respectively. We have recently looked at the effects of chloroquine on the metabolic syndrome in humans which showed that small doses given for a short period of time would reduce insulin resistance in patients with the metabolic syndrome. Several population studies have shown similar effects with hydroxychloroquine. Since hydroxychloroquine is similar to chloroquine, we thus expect similar effects on blood glucose, blood pressure and blood cholesterol in type 2 diabetes. This offers a unique opportunity to develop a novel approach for lowering blood pressure, lipids (cholesterol and triglycerides), and glucose in people at risk for heart disease
Interventions
DRUGHydroxychloroquine
200mg twice daily
200mg placebo twice daily
Sponsors
Washington University School of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Subjects between the age of 18 and 75, either gender, any ethnic group * Subjects must have type 2 diabetes and the following: * A1c of 6.5-9.0% * Treated with at least 1000 mg of metformin daily with or without a dipeptidyl peptidase-4(DPP4)inhibitor, a sulfonylurea (glipizide, glyburide, glimepiride),bromocriptine or colesevelam. * Subjects should have a BMI \>27
Exclusion criteria
* Prior treatment with chloroquine or hydroxychloroquine as follows: 1. any exposure in the past 2 years, 2. \>30 days of therapy if exposure was between 2 and 5 years ago, 3. \>90 days of therapy if exposure was between 5 and 10 years ago, 4. \>6 months of therapy if exposure was 10 to 20 years ago, 5. \>1 year of therapy if exposure was 20 to 30 years ago, 6. No limit if last exposure was \>30 years ago, e.g. during the Vietnam conflict. * Morbid obesity (BMI \>45) * Coronary artery disease or other vascular disease * History of stroke * Serum creatinine \>-4 mg/dl for women and \>-5 mg/dl for men. * Seizure disorder * History of psoriasis * Hematologic disorders, including anemia (WHO criteria for anemia:hemoglobin \<13g/dL in men and \<12 g/dL in women) * Current malignancy or active treatment for recurrence prevention,e.g. tamoxifen. Cancer considered to be cured, either as a result of surgery or other treatment is not exclusionary. * Asthma requiring daily beta agonist therapy or intermittent oral steroids is exclusionary. Inhaled steroids are acceptable. Obstructive sleep apnea will be allowed if continuous positive airway pressure(CPAP) or other therapy has been stable for 6 months. Other active respiratory diseases are excluded. * Treatment with 50mg or greater of Metoprolol or treatment with digoxin * Liver disease, or Liver Function Test \>2 times normal * Active infection (including HIV) * Serious illness requiring ongoing medical care or medication * Treatment with atypical anti-psychotic medication. Treatment with any other medication for psychiatric illness, unless on a stable dose for 6 weeks prior to enrollment. Patients with unstable psychiatric disorders are excluded per the decision of the study MD regardless of medication history. * Taking any of the following lipid lowering medications: niacin, fibrates, and greater than 1 gm/day of fish oils * Uncontrolled hypertension (BP \>150/90 mm Hg) at enrollment * Need for daily Over The Counter medications, or currently taking cimetidine or \>1000 IU vitamin E daily and unwilling to reduce or discontinue vitamin E or discontinue cimetidine for the duration of the study. Patients taking more than 1000 IU vitamin E daily should reduce or discontinue the vitamin for 30 days before randomization. * Pregnant or lactating women, or women intending to become pregnant * Women not using adequate birth control (hormonal birth control is acceptable, also double barrier) * QT corrected \>450 msec on screening ECG * Glucose-6-phosphate dehydrogenase (G6PD) deficiency
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Effect of HCQ on Fasting Blood Glucose | 4 weeks | determined by fasting blood glucose performed at baseline and follow-up |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Effect of HCQ on Fasting Low Density Lipoprotein | 4 weeks | determined by lipid profile with calculated LDL performed at baseline and follow-up |
Countries
United States
Participant flow
Pre-assignment details
Two participants withdrew consent prior to the baseline visit. After the baseline visit, participants were randomized to either the hydroxychloroquine group or the placebo group.
Participants by arm
| Arm | Count |
|---|---|
| Hydroxychloroquine hydroxychloroquine twice daily for 4 weeks
Hydroxychloroquine: 200mg twice daily | 7 |
| Placebo hydroxychloroquine placebo twice daily for 4 weeks
Hydroxychloroquine Placebo: 200mg placebo twice daily | 9 |
| Total | 16 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | incomplete visit/missing data | 3 | 2 |
Baseline characteristics
| Characteristic | Hydroxychloroquine | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 3 Participants | 5 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants | 6 Participants | 11 Participants |
| Age, Continuous | 55 years STANDARD_DEVIATION 14 | 61 years STANDARD_DEVIATION 7 | 59 years STANDARD_DEVIATION 10 |
| Race/Ethnicity, Customized African American | 2 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized Caucasian | 5 Participants | 8 Participants | 13 Participants |
| Sex: Female, Male Female | 4 Participants | 1 Participants | 5 Participants |
| Sex: Female, Male Male | 3 Participants | 8 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 11 |
| other Total, other adverse events | 3 / 10 | 1 / 11 |
| serious Total, serious adverse events | 0 / 10 | 0 / 11 |
Outcome results
Primary
Effect of HCQ on Fasting Blood Glucose
determined by fasting blood glucose performed at baseline and follow-up
Time frame: 4 weeks
Population: randomized participants
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Hydroxychloroquine | Effect of HCQ on Fasting Blood Glucose | Follow-up Glucose (mg/dL) | 165.9 mg/dL | Standard Deviation 67.1 |
| Hydroxychloroquine | Effect of HCQ on Fasting Blood Glucose | Baseline Glucose (mg/dL) | 186.9 mg/dL | Standard Deviation 64.5 |
| Placebo | Effect of HCQ on Fasting Blood Glucose | Baseline Glucose (mg/dL) | 163.1 mg/dL | Standard Deviation 22.5 |
| Placebo | Effect of HCQ on Fasting Blood Glucose | Follow-up Glucose (mg/dL) | 158.8 mg/dL | Standard Deviation 38.7 |
p-value: 0.05t-test, 2 sided
Secondary
Effect of HCQ on Fasting Low Density Lipoprotein
determined by lipid profile with calculated LDL performed at baseline and follow-up
Time frame: 4 weeks
Population: Randomized Participants
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Hydroxychloroquine | Effect of HCQ on Fasting Low Density Lipoprotein | Baseline - LDL (mg/dL) | 90.4 mg/dL | Standard Deviation 21.4 |
| Hydroxychloroquine | Effect of HCQ on Fasting Low Density Lipoprotein | Follow-up - LDL (mg/dL) | 72.4 mg/dL | Standard Deviation 21.6 |
| Placebo | Effect of HCQ on Fasting Low Density Lipoprotein | Baseline - LDL (mg/dL) | 92.8 mg/dL | Standard Deviation 26.2 |
| Placebo | Effect of HCQ on Fasting Low Density Lipoprotein | Follow-up - LDL (mg/dL) | 87.7 mg/dL | Standard Deviation 23.8 |