Hydroxychloroquine Versus Pioglitazone in Combination Treatment for Type 2 Diabetes Mellitus
Condition: Diabetes Mellitus Type 2 With Hyperglycemia
MeSH terms: Diabetes Mellitus; Hyperglycemia; Diabetes Mellitus, Type 2
Intervention: Hydroxychloroquine; Pioglitazone
Intervention description: Anti-inflammatory and anti-malarial agent; Anti-hyperglycemic agent
Intervention MeSH terms: Pioglitazone; Hydroxychloroquine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 22.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Glucose Control; Inflammation

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.
    

Eligibility criteria:

        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.