Clinical trial NCT01456650: R230C and C230C Variants of ABCA1 and Glyburide Response
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Type 2 Diabetes
Keywords: Type 2 diabetes
ABCA1 alleles
Glyburide
Lead sponsor: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Sponsor class: OTHER
First posted: 2011-10-21
Enrollment: 85
Sex: ALL
Minimum age (years): 20
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

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%

Eligibility criteria: 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

Primary outcomes:
measure: Change in plasma fasting glucose
timeFrame: 20 weeks
Secondary outcomes:
measure: HbA1c levels
timeFrame: 20 weeks
Other outcomes:
Locations:
city: Mexico City
country: Mexico
facility: Instituto Nacional de Ciencias Medicas y Nutricion
state: DF
Study officials:
affiliation: Instituto Nacional de Ciencias Medicas y Nutricion
name: Carlos A Aguilar-Salinas, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.