Hydroxychloroquine Versus Pioglitazone in Combination Treatment for Type 2 Diabetes Mellitus

Study Overview
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Brief Summary
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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
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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.

Official Title
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Comparing the Effects of Hydroxychloroquine (HCQ) to Pioglitazone in Type 2 Diabetic Patients Failing Maximal Doses of Metformin Plus a Sulfonylurea

Conditions
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Diabetes Mellitus Type 2 With Hyperglycemia

Intervention / Treatment
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* Drug: Hydroxychloroquine
* Drug: Pioglitazone


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hydroxychloroquine<br>Treatment with hydroxychloroquine 400 mg (2 x 200 mg tablets) po once daily x 4 months | Drug: Hydroxychloroquine<br>* Anti-inflammatory and anti-malarial agent<br>* Other names: Plaquenil;|
| Active Comparator: Pioglitazone<br>Treatment with pioglitazone 45 mg po (1 tablet) once daily x 4 months | Drug: Pioglitazone<br>* Anti-hyperglycemic agent<br>* Other names: Actos;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hemoglobin A1c | Glycemic control | 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fasting Plasma Glucose | Fasting glucose level | 4 months | 
| Percent of Subjects Achieving HbA1c < 7.5% | Percent of subjects achieving a HbA1c level < 7.5% | 4 months | 
| Weight | Body weight | 4 months | 
| Body Mass Index | Body mass index (BMI) | 4 months | 
| HOMA-IR | Insulin resistance by the HOMA model | 4 months | 
| QUICKI | Insulin resistance by the QUICKI model | 4 months | 
| Hs-CRP | Highly-sensitive C-reactive protein (inflammatory marker) | 4 months | 
| Leucocyte Count | White cell count (surrogate marker of inflammation) | 4 months | 
| Hypoglycemic Events | Number of hypoglycemic events | 4 months | 
| Adverse Events | All other adverse events other than hypoglycemia | 4 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Glucose Control, Inflammation