Hydroxychloroquine Versus Pioglitazone in Combination Treatment for Type 2 Diabetes Mellitus

Phase 2

Terminated

Conditions: Diabetes Mellitus Type 2 With Hyperglycemia

Interventions: Drug: Pioglitazone
Drug: Hydroxychloroquine

Registration Number: NCT02303405

Lead Sponsor: Charles Drew University of Medicine and Science

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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 22

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Pioglitazone	Pioglitazone	Treatment with pioglitazone 45 mg po (1 tablet) once daily x 4 months
Hydroxychloroquine	Hydroxychloroquine	Treatment with hydroxychloroquine 400 mg (2 x 200 mg tablets) po once daily x 4 months

Primary Outcome Measures

Name	Time	Method
Hemoglobin A1c	4 months	Glycemic control

Secondary Outcome Measures

Name	Time	Method
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%
Weight	4 months	Body weight
Body Mass Index	4 months	Body mass index (BMI)
HOMA-IR	4 months	Insulin resistance by the HOMA model
QUICKI	4 months	Insulin resistance by the QUICKI model
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