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Sulphonylurea Receptor Mutation and Responsiveness to Gliclazide - a Pilot Proof of Concept, Randomised Cross-over Study

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02201602
Recruitment Status : Completed
First Posted : July 28, 2014
Last Update Posted : September 1, 2016
Information provided by (Responsible Party):
Su Chi Lim, Khoo Teck Puat Hospital

Brief Summary:
Gliclazide has greater glucose lowering efficacy than glibenclamide among type 2 diabetes mellitus patients with minor haplotype (K23/A1369) at the KCNJ11/ABCC gene locations.

Condition or disease Intervention/treatment Phase
Diabetes Drug: Gliclazide Drug: Glibenclamide Phase 4

Detailed Description:
Sulphonylurea (SU) is a glucose-lowering agent used widely to treat type 2 diabetes mellitus (T2DM). SU promotes insulin secretion from the pancreatic islet beta cell via binding and inhibition of the ATP-sensitive potassium (KATP) channel. The KATP channel is made up of two subcomponents, an inner Kir6.2 K+ channel (coded by the KCNJ11 gene) and an outer SU receptor 1 (SUR1) (coded by the ABCC8 gene). Although all SUs are mechanistically similar in terms of increasing insulin secretion, they bind to distinct regions of Kir 6.2 and SUR1 to exert their function. Different types of SU (e.g. tolbutamide, glibenclamide, glipizide, glimepiride and gliclazide) can therefore be grouped by their binding sites (A/B/A+B site) on the KATP channel [3]. Interestingly, the KCNJ11 E23K (rs5219) variant was shown to confer susceptibility to T2DM and the ABCC8 S1369A (rs757110) variant was found to be in complete linkage disequilibrium with it i.e. inherited together as a genetic block (haplotype). A recent in vitro molecular study suggested that the minor haplotype (K23/A1369) of KATP channel is sensitive to inhibition by gliclazide (binds to A-site) but not glibenclamide (binds to A+B site), and that the increased responsiveness to gliclazide was largely due to the A1369 allele. Understanding how the response to these two SUs may vary with the presence of the minor haplotype (K23/A1369) would therefore be beneficial for customization of patient treatment to achieve better clinical outcomes.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 8 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Sulphonylurea Receptor Mutation and Responsiveness to Gliclazide - a Pilot Proof of Concept, Randomised Cross-over Study
Study Start Date : August 2014
Actual Primary Completion Date : June 2016
Actual Study Completion Date : July 2016

Resource links provided by the National Library of Medicine

Drug Information available for: Glyburide

Arm Intervention/treatment
Experimental: Gliclazide
Gliclazide, 80 mg tablet, half to maximal dose, 3 weeks
Drug: Gliclazide
Other Names:
  • Sun-Glizide
  • SIN09350P

Active Comparator: Glibenclamide
Glibenclamide, 5 mg tablet, half to maximal dose, 3 weeks
Drug: Glibenclamide
Other Names:
  • Benil
  • SIN07284P

Primary Outcome Measures :
  1. Mean blood glucose level [ Time Frame: 6 days ]

Secondary Outcome Measures :
  1. Glycemic variability [ Time Frame: 6 days ]
    Glycemic variability will be assessed using the EasyGV software ( which is capable of calculating 10 different measures of glycemic variability from continuous glucose monitoring data, such as Standard Deviation (SD) and M-value, mean amplitude of glycemic excursions (MAGE).

Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Type 2 diabetes
  • Age 21-65
  • HbA1c >8.0% on two consecutive visits

Exclusion Criteria:

  • Currently taking insulin at a regime more complex than basal insulin
  • Not willing to perform self-blood glucose monitoring (SBGM)
  • Renal impairment i.e. eGFR<50mls/min
  • Pregnancy or unwilling to practice adequate contraception
  • Taking other medications that may affect blood glucose e.g. systemic glucocorticoids.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02201602

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Khoo Teck Puat Hospital
Singapore, Singapore, 768828
Sponsors and Collaborators
Khoo Teck Puat Hospital
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Principal Investigator: Su Chi Lim, MBBS, PhD Khoo Teck Puat Hospital
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Responsible Party: Su Chi Lim, Senior Consultant, Khoo Teck Puat Hospital Identifier: NCT02201602    
Other Study ID Numbers: Gliclazide
First Posted: July 28, 2014    Key Record Dates
Last Update Posted: September 1, 2016
Last Verified: August 2016
Keywords provided by Su Chi Lim, Khoo Teck Puat Hospital:
Additional relevant MeSH terms:
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Hypoglycemic Agents
Physiological Effects of Drugs