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

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ClinicalTrials.gov Identifier: NCT02201602
Recruitment Status : Completed
First Posted : July 28, 2014
Last Update Posted : September 1, 2016
Sponsor:
Information provided by (Responsible Party):
Su Chi Lim, Khoo Teck Puat Hospital

Tracking Information
First Submitted Date  ICMJE July 22, 2014
First Posted Date  ICMJE July 28, 2014
Last Update Posted Date September 1, 2016
Study Start Date  ICMJE August 2014
Actual Primary Completion Date June 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 25, 2014)
Mean blood glucose level [ Time Frame: 6 days ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 25, 2014)
Glycemic variability [ Time Frame: 6 days ]
Glycemic variability will be assessed using the EasyGV software (http://www.phc.ox.ac.uk/research/diabetes/software/easygv/) 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).
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Sulphonylurea Receptor Mutation and Responsiveness to Gliclazide - a Pilot Proof of Concept, Randomised Cross-over Study
Official Title  ICMJE Sulphonylurea Receptor Mutation and Responsiveness to Gliclazide - a Pilot Proof of Concept, Randomised Cross-over Study
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.
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Diabetes
Intervention  ICMJE
  • Drug: Gliclazide
    Other Names:
    • Sun-Glizide
    • SIN09350P
  • Drug: Glibenclamide
    Other Names:
    • Benil
    • SIN07284P
Study Arms  ICMJE
  • Experimental: Gliclazide
    Gliclazide, 80 mg tablet, half to maximal dose, 3 weeks
    Intervention: Drug: Gliclazide
  • Active Comparator: Glibenclamide
    Glibenclamide, 5 mg tablet, half to maximal dose, 3 weeks
    Intervention: Drug: Glibenclamide
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 31, 2016)
8
Original Estimated Enrollment  ICMJE
 (submitted: July 25, 2014)
15
Actual Study Completion Date  ICMJE July 2016
Actual Primary Completion Date June 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 21 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Singapore
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02201602
Other Study ID Numbers  ICMJE Gliclazide
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Su Chi Lim, Khoo Teck Puat Hospital
Study Sponsor  ICMJE Khoo Teck Puat Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Su Chi Lim, MBBS, PhD Khoo Teck Puat Hospital
PRS Account Khoo Teck Puat Hospital
Verification Date August 2016

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