Hydroxychloroquine Versus Pioglitazone in Combination Treatment for Type 2 Diabetes Mellitus

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

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.

Study Overview

• Status: Terminated
• Conditions: Diabetes Mellitus Type 2 With Hyperglycemia
• Intervention / Treatment: Drug: Hydroxychloroquine; Drug: Pioglitazone

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 Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90059
      • Charles Drew University of Medicine and Science

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Charles Drew University of Medicine and Science

Study record dates

Study Major Dates

• Study Start: November 1, 2014
• Primary Completion (Actual): November 1, 2017
• Study Completion (Actual): November 1, 2017

Study Registration Dates

• First Submitted: November 25, 2014
• First Submitted That Met QC Criteria: November 26, 2014
• First Posted (Estimate): November 27, 2014

Study Record Updates

• Last Update Posted (Actual): October 20, 2022
• Last Update Submitted That Met QC Criteria: September 23, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: Inflammation; Glucose Control
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Hyperglycemia; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Pioglitazone; Hydroxychloroquine
• Other Study ID Numbers: 14-01-2419

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No