Diabetes Mellitus Type 2 With Hyperglycemia
Conditions
Keywords
Glucose Control, Inflammation
Brief summary
A 4-month, randomized, prospective, open-label comparison trial of hydroxychloroquine vs. pioglitazone in type 2 diabetic patients inadequately controlled on maximally tolerated doses of metformin plus a sulfonylurea.
Detailed description
A 4-month, randomized, prospective, open-label comparison trial of 4 months of hydroxychloroquine vs. pioglitazone in type 2 diabetic patients inadequately controlled on maximally tolerated doses of metformin plus a sulfonylurea.
Interventions
DRUGHydroxychloroquine
Anti-inflammatory and anti-malarial agent
DRUGPioglitazone
Anti-hyperglycemic agent
Sponsors
Charles Drew University of Medicine and Science
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Male or female, age 18-75, inclusive * Known type 2 diabetes (diagnosed according to 1997 ADA diagnostic criteria) * At least 3 months of treatment with maximum tolerated doses of metformin and a sulfonylurea * Hemoglobin A1c ≥ 7.5% and \< 11.0% * Body mass index (BMI) \< 45 kg/m2 * Able to comply with all scheduled visits and requirements of the protocol
Exclusion criteria
* Any contraindications to the use of metformin or a sulfonylurea * Extreme hyperglycemia (FPG ≥ 300 mg/dL), symptoms of polyuria or polydipsia, or Hemoglobin A1c ≥ 11.0% * Current use of insulin; history or clinical suspicion of type 1 diabetes mellitus * Symptomatic hypoglycemia occurring at an average frequency \> once per day * Highly erratic dietary schedules, extremely food insecure households, or homelessness that may adversely affect good glycemic control, as judged by the investigators * Occupations that involve regular operation of motor vehicles or other heavy machinery that may pose a hazard in the event of unanticipated blurred vision * Known history of Class III or IV heart failure, cardiac arrhythmias, severe peripheral edema, advanced osteoporosis, documented bladder malignancies, or other intolerance to pioglitazone * Known history of collagen vascular disorders, glucose-6-phosphate dehydrogenase deficiency, hematologic disorders, psoriasis, or any known intolerance to hydroxychloroquine * Known history of pre-proliferative or proliferative retinopathy, or any clinically significant retinal abnormalities noted on the patient's most recent (i.e., within 1 year) ophthalmologic exam; subjects who have not received their routine annual ophthalmologic surveillance for diabetic retinopathy within the past year must have their annual surveillance performed before screening * An estimated GFR (by the Modification of Diet in Renal Disease (MDRD) formula) \< 45 mL/min, or a history of nephrotic syndrome (defined as a spot urine protein-creatinine ratio of \> 3500 mg per g urine creatinine) * Subjects with active hemoglobin abnormalities that render the Hemoglobin A1c measurement unreliable * History of any clinically significant hepatic, cardiovascular, infectious, dermatologic, psychiatric, or other major systemic disease that, in the opinion of the investigator, may make the use of pioglitazone or hydroxychloroquine unsafe, or otherwise make the interpretation of the data difficult. * Female subjects of childbearing potential who are sexually active and not using a reliable form of contraception or do not agree to use a reliable form of contraception. Reliable forms of contraception include systemic contraceptives (oral, implant or injection), diaphragm with spermicide, cervical cap, IUD, or condoms with spermicide. * Current pregnancy or lactation. * Subjects who will likely require or initiate therapy with drugs that may interfere with glucose metabolism during the course of the study (e.g., glucocorticoids). * Subjects who are in another investigational study or have received another investigational medication within 30 days of study entry * Subjects who are unable or unwilling to give informed consent, comply with all components of the study protocol, attend all scheduled follow-up visits, or present other barriers that would make the implementation of the protocol unusually difficult.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hemoglobin A1c | 4 months | Glycemic control |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Weight | 4 months | Body weight |
| Body Mass Index | 4 months | Body mass index (BMI) |
| HOMA-IR | 4 months | Insulin resistance by the HOMA model |
| Fasting Plasma Glucose | 4 months | Fasting glucose level |
| Percent of Subjects Achieving HbA1c < 7.5% | 4 months | Percent of subjects achieving a HbA1c level \< 7.5% |
| Hs-CRP | 4 months | Highly-sensitive C-reactive protein (inflammatory marker) |
| Leucocyte Count | 4 months | White cell count (surrogate marker of inflammation) |
| Hypoglycemic Events | 4 months | Number of hypoglycemic events |
| Adverse Events | 4 months | All other adverse events other than hypoglycemia |
| QUICKI | 4 months | Insulin resistance by the QUICKI model |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Hydroxychloroquine Treatment with hydroxychloroquine 400 mg (2 x 200 mg tablets) po once daily x 4 months
Hydroxychloroquine: Anti-inflammatory and anti-malarial agent | 15 |
| Pioglitazone Treatment with pioglitazone 45 mg po (1 tablet) once daily x 4 months
Pioglitazone: Anti-hyperglycemic agent | 7 |
| Total | 22 |
Baseline characteristics
| Characteristic | Hydroxychloroquine | Pioglitazone | Total |
|---|---|---|---|
| Age, Continuous | 53 years STANDARD_DEVIATION 10 | 57 years STANDARD_DEVIATION 13 | 54 years STANDARD_DEVIATION 11 |
| Body Mass Index | 35.3 kg per meter squared STANDARD_DEVIATION 5.7 | 34.1 kg per meter squared STANDARD_DEVIATION 5.2 | 34.9 kg per meter squared STANDARD_DEVIATION 5.4 |
| Diabetes Duration | 5.1 years STANDARD_DEVIATION 3.1 | 7.8 years STANDARD_DEVIATION 4.3 | 6.0 years STANDARD_DEVIATION 3.6 |
| Fasting Plasma Glucose | 179 mg/dL STANDARD_DEVIATION 53 | 170 mg/dL STANDARD_DEVIATION 50 | 176 mg/dL STANDARD_DEVIATION 51 |
| Hemoglobin A1c | 8.6 % STANDARD_DEVIATION 1 | 9.1 % STANDARD_DEVIATION 0.7 | 8.7 % STANDARD_DEVIATION 0.9 |
| hs-CRP | 6.2 mg/L STANDARD_DEVIATION 6.7 | 8.8 mg/L STANDARD_DEVIATION 7.2 | 7.0 mg/L STANDARD_DEVIATION 6.8 |
| Leucocyte Count | 8.4 x 10^9 cells/L STANDARD_DEVIATION 1.6 | 7.8 x 10^9 cells/L STANDARD_DEVIATION 1.4 | 8.2 x 10^9 cells/L STANDARD_DEVIATION 1.5 |
| Race/Ethnicity, Customized Black | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Latino | 12 Participants | 7 Participants | 19 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Female | 11 Participants | 6 Participants | 17 Participants |
| Sex: Female, Male Male | 4 Participants | 1 Participants | 5 Participants |
| Weight | 85.7 kg STANDARD_DEVIATION 14.3 | 83.7 kg STANDARD_DEVIATION 18.2 | 85.0 kg STANDARD_DEVIATION 15.2 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 7 |
| other Total, other adverse events | 0 / 15 | 1 / 7 |
| serious Total, serious adverse events | 1 / 15 | 0 / 7 |
Outcome results
Primary
Hemoglobin A1c
Glycemic control
Time frame: 4 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Hydroxychloroquine | Hemoglobin A1c | 7.4 % of hemoglobin | Standard Deviation 0.9 |
| Pioglitazone | Hemoglobin A1c | 6.3 % of hemoglobin | Standard Deviation 0.2 |
Secondary
Adverse Events
All other adverse events other than hypoglycemia
Time frame: 4 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Hydroxychloroquine | Adverse Events | 0 Events |
| Pioglitazone | Adverse Events | 1.0 Events |
Secondary
Body Mass Index
Body mass index (BMI)
Time frame: 4 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Hydroxychloroquine | Body Mass Index | 35.2 kg per square meter | Standard Deviation 6 |
| Pioglitazone | Body Mass Index | 35.5 kg per square meter | Standard Deviation 5.4 |
Secondary
Fasting Plasma Glucose
Fasting glucose level
Time frame: 4 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Hydroxychloroquine | Fasting Plasma Glucose | 147 mg/dL | Standard Deviation 33 |
| Pioglitazone | Fasting Plasma Glucose | 105 mg/dL | Standard Deviation 21 |
Secondary
HOMA-IR
Insulin resistance by the HOMA model
Time frame: 4 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Hydroxychloroquine | HOMA-IR | 3.91 uU/mL*mg/dL | Standard Deviation 2.92 |
| Pioglitazone | HOMA-IR | 1.48 uU/mL*mg/dL | Standard Deviation 0.79 |
Secondary
Hs-CRP
Highly-sensitive C-reactive protein (inflammatory marker)
Time frame: 4 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Hydroxychloroquine | Hs-CRP | 4.2 mg/L | Standard Deviation 3.8 |
| Pioglitazone | Hs-CRP | 3.3 mg/L | Standard Deviation 3.7 |
Secondary
Hypoglycemic Events
Number of hypoglycemic events
Time frame: 4 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Hydroxychloroquine | Hypoglycemic Events | 0 Events |
| Pioglitazone | Hypoglycemic Events | 6.0 Events |
Secondary
Leucocyte Count
White cell count (surrogate marker of inflammation)
Time frame: 4 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Hydroxychloroquine | Leucocyte Count | 7.7 x 10^9 cells/ L | Standard Deviation 1.9 |
| Pioglitazone | Leucocyte Count | 6.8 x 10^9 cells/ L | Standard Deviation 1.7 |
Secondary
Percent of Subjects Achieving HbA1c < 7.5%
Percent of subjects achieving a HbA1c level \< 7.5%
Time frame: 4 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Hydroxychloroquine | Percent of Subjects Achieving HbA1c < 7.5% | 10 Participants |
| Pioglitazone | Percent of Subjects Achieving HbA1c < 7.5% | 7 Participants |
Secondary
QUICKI
Insulin resistance by the QUICKI model
Time frame: 4 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Hydroxychloroquine | QUICKI | 0.32 (Log(uU/dL)+Log(mg/dL))^-1 | Standard Deviation 0.03 |
| Pioglitazone | QUICKI | 0.38 (Log(uU/dL)+Log(mg/dL))^-1 | Standard Deviation 0.05 |
Secondary
Weight
Body weight
Time frame: 4 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Hydroxychloroquine | Weight | 85.4 kilograms | Standard Deviation 14.5 |
| Pioglitazone | Weight | 87.0 kilograms | Standard Deviation 17.9 |