R230C and C230C Variants of ABCA1 and Glyburide Response

Effect of the R230C Variant of the ATP-binding Cassette Transporter A1 (ABCA1) Gene on the Response to Treatment With Glibenclamide in Patients With Type 2 Diabetes Mellitus

The objective of the study is to know if the R230C and C230C variants of the ATP-binding cassette transporter A1 (ABCA1) gene are associated with a smaller glucose lowering effect compared to the wild type allele (R230R) in patients with type 2 diabetes.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Drug: Glyburide

Detailed Description

Specific objectives:

1. In patients with type 2 diabetes stratified by the existence of the risk alleles (R230C/C230C) or the wild variant (R230R) of ABC-A1, compare the changes resulting from the treatment with glibenclamide on following continuous variables:

   • Fasting glucose
   • Percentage reduction
   • Hemoglobin A1c,
   • Cholesterol, triglycerides, HDL cholesterol, LDL cholesterol
   • Weight

2. In patients with type 2 diabetes stratified by the existence of the risk alleles (R230C/C230C) or the wild variant (R230R) of ABC-A1, compare the changes resulting from the treatment with glibenclamide on following binomial variables:

   • Number of cases that reach fasting plasma glucose lower than 110 mg/dl
   • Number of cases that reach an HbA1c less than 7%

• Study Type: Interventional
• Enrollment (Actual): 85
• Phase: Phase 4

Contacts and Locations

Study Locations

• Mexico
  • DF
    • Mexico City, DF, Mexico, 14000
      • Instituto Nacional de Ciencias Médicas y Nutrición

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 79 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adults 20 to 79 years
• Body mass index >18 and 39.9 ≤
• Men or women
• Mexicans mestizos.
• Moderate hyperglycemia (126 to 250 mg/dl and HbA1c levels between 7 and 10%) despite being treated with a dietary program in combination or not with metformin (2 g/d).

Exclusion Criteria:

• Patients with chronic complications of diabetes: ischemic heart disease, stroke, proliferative retinopathy or blindness, albuminuria, chronic diarrhea, gastroparesis, non-traumatic amputation of lower limbs.
• Patients with any monogenic syndrome, obesity, diabetes or hypoalphalipoproteinemia
• Patients with acquired diseases that produce secondarily obesity or diabetes.
• Treatment with anorexigenics or accelerate weight loss at the time of the selection.
• Cardiovascular event in the 6 months prior to study entry.
• Steroids, chemotherapy, immunosuppressive or radiotherapy.
• Infections or concurrent acute diseases.
• Catabolic diseases such as cancer or AIDS
• Pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: Glyburide; Patients in which the fasting glucose persisted above the treatment goal (fasting glucose <126 mg/dl) after a 4 week diet period will receive glyburide. The dose of the medication will be adjusted based on the results of fasting glucose values. At each visit patients will return the leftover tablets; counts of the tablets will be the method for measuring the adherence to treatment. The medical study participants who decided to doses of glibenclamide will not know the allele of ABCA1 gene under study.

Drug: Glyburide; Patients in which the fasting glucose persisted above the treatment goal ( fasting plasma glucose above 126 mg/dl) will receive glyburide. The dose of the medication will be adjusted based on the result of blood glucose using the following table: Fasting glucose 126 to 140 mg/dl: 2.5 mg/day (half tablet in the morning) 141 to 180 mg/dl: 5 mg/day (a tablet in the morning) 181 220 mg/dl: 7.5 mg/day (a tablet in the morning and half tablet per night) 221 to 250 mg/dl: 10 mg/day (a tablet in the morning) and a tablet in the evening.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in plasma fasting glucose	The effects of the alleles under study on the glucose lowering effect of glyburide will be assessed in 20 week study. Diet and exercise will be controlled per protocol	20 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
HbA1c levels	20 weeks

Collaborators and Investigators

• Sponsor: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
• Investigators: Principal Investigator: Carlos A Aguilar-Salinas, MD, Instituto Nacional de Ciencias Médicas y Nutrición

Publications and helpful links

General Publications

• Aguilar-Salinas CA, Munoz-Hernandez LL, Cobos-Bonilla M, Ramirez-Marquez MR, Ordonez-Sanchez ML, Mehta R, Medina-Santillan R, Tusie-Luna MT. The R230C variant of the ATP binding cassette protein A1 (ABCA1) gene is associated with a decreased response to glyburide therapy in patients with type 2 diabetes mellitus. Metabolism. 2013 May;62(5):638-41. doi: 10.1016/j.metabol.2012.11.006. Epub 2012 Dec 27.

Study record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (ACTUAL): November 1, 2012
• Study Completion (ACTUAL): December 1, 2012

Study Registration Dates

• First Submitted: October 19, 2011
• First Submitted That Met QC Criteria: October 20, 2011
• First Posted (ESTIMATE): October 21, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): January 15, 2014
• Last Update Submitted That Met QC Criteria: January 14, 2014
• Last Verified: January 1, 2014

More Information

Terms related to this study

• Keywords: Type 2 diabetes; Glyburide; ABCA1 alleles
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Glyburide
• Other Study ID Numbers: INNSZ-ABCA1