Hydroxychloroquine Versus Pioglitazone in Combination Treatment for Type 2 Diabetes Mellitus

Sponsor

Charles Drew University of Medicine and Science (Other)

Overall Status

Terminated

CT.gov ID

NCT02303405

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

0.5

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus Type 2 With Hyperglycemia	Drug: Hydroxychloroquine Drug: Pioglitazone	Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

17 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Nov 1, 2014

Actual Primary Completion Date :

Nov 1, 2017

Actual Study Completion Date :

Nov 1, 2017

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: Hydroxychloroquine

Treatment with hydroxychloroquine 400 mg (2 x 200 mg tablets) po once daily x 4 months

Drug: Hydroxychloroquine

Anti-inflammatory and anti-malarial agent

Other Names:

Plaquenil

Active Comparator: Pioglitazone

Treatment with pioglitazone 45 mg po (1 tablet) once daily x 4 months

Drug: Pioglitazone

Anti-hyperglycemic agent

Other Names:

Actos

Outcome Measures

Primary Outcome Measures

Hemoglobin A1c [4 months]
Glycemic control

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.