R230C and C230C Variants of ABCA1 and Glyburide Response

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Carlos Aguilar, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
ClinicalTrials.gov Identifier:
NCT01456650
First received: October 19, 2011
Last updated: January 14, 2014
Last verified: January 2014

October 19, 2011
January 14, 2014
March 2011
November 2012   (final data collection date for primary outcome measure)
Change in plasma fasting glucose [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]
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
Same as current
Complete list of historical versions of study NCT01456650 on ClinicalTrials.gov Archive Site
HbA1c levels [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
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.

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%
Interventional
Phase 4
Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Basic Science
Type 2 Diabetes
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.

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.
Intervention: Drug: Glyburide
Aguilar-Salinas CA, Muñoz-Hernandez LL, Cobos-Bonilla M, Ramírez-Márquez MR, Ordoñez-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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
85
December 2012
November 2012   (final data collection date for primary outcome measure)

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
Both
20 Years to 79 Years
No
Contact information is only displayed when the study is recruiting subjects
Mexico
 
NCT01456650
INNSZ-ABCA1
No
Carlos Aguilar, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Not Provided
Principal Investigator: Carlos A Aguilar-Salinas, MD Instituto Nacional de Ciencias Medicas y Nutricion
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
January 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP