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Low dosE GlibENclamide in Diabetes Part A (LEGEND-A)

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.
 
ClinicalTrials.gov Identifier: NCT02830048
Recruitment Status : Completed
First Posted : July 12, 2016
Last Update Posted : May 31, 2017
Sponsor:
Collaborator:
Oxford University Hospitals NHS Trust
Information provided by (Responsible Party):
University of Oxford

Brief Summary:

Diabetes is a chronic condition that affects 1 in 16 people in the UK, and leads to difficulty controlling blood sugar levels. This is due to an imbalance between two main hormones: insulin, which lowers blood sugar, and glucagon, which causes it to rise. Most current anti-diabetic medications work to improve insulin levels, however research is now shifting to better understand how glucagon levels play a key role in this disease.

Glibenclamide is a type of anti-diabetic medication (sulfonylurea) which is commonly used to increase the amount of insulin released by the pancreatic beta-cells. Studies in mice and human cells from donors with type 2 diabetes have shown that sulfonylureas can also improve glucagon levels when used in very small doses by working on different cells in the pancreas (alpha-cells).

The aim of this study is to find out whether low doses of glibenclamide can improve glucagon levels in patients with type 2 diabetes, and whether in the future this could be used to better control high blood sugar levels, without the risk of causing low blood sugar.

Participants with type 2 diabetes who are diet-controlled or on metformin will be given a liquid containing a low dose of glibenclamide. They will need to attend the OCDEM Clinical Research Unit at the Churchill Hospital, Oxford, for early morning blood tests every 3-4 days over a period of 3 weeks. A continuous glucose monitor will also be fitted during this time.

This study is funded by the NIHR OxBRC.


Condition or disease Intervention/treatment Phase
Diabetes Mellitus, Type 2 Drug: Glibenclamide Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 16 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Low-dose Glibenclamide in Type 2 Diabetes Mellitus - Part A
Study Start Date : July 2016
Actual Primary Completion Date : March 9, 2017
Actual Study Completion Date : March 9, 2017

Resource links provided by the National Library of Medicine

Drug Information available for: Glyburide

Arm Intervention/treatment
Experimental: Glibenclamide dose titration
Increasing doses of glibenclamide oral suspension from 0.3mg/day to 6mg/day.
Drug: Glibenclamide
Other Name: GlibenTek




Primary Outcome Measures :
  1. Decrease in fasting plasma glucagon concentration [ Time Frame: After 3-4 days of treatment at each dose increment ]
    Concentration of plasma glucagon using fasting blood samples prior to each dose change.


Secondary Outcome Measures :
  1. Overall improvement in glycaemic control throughout the day [ Time Frame: After 3-4 days of treatment at each dose increment ]
    Change in the percentage of Continuous Glucose Monitoring (CGM) readings under 4 mmol/L, between 4-10 mmol/L and above 10 mmol/L before starting glibenclamide and prior to each change in dose.

  2. Effect on fasting glucose, insulin and C-peptide levels [ Time Frame: After 3-4 days of treatment at each dose increment ]
    Concentration of glucose, insulin and C-peptide using fasting blood samples prior to each dose change.

  3. Pre-dose plasma concentration of glibenclamide [ Time Frame: After 3-4 days of treatment at each dose increment ]
    Concentration of plasma glibenclamide using fasting blood samples prior to each dose change.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of T2DM.
  • Age 18 years or over.
  • Diet controlled or on metformin only for diabetic control.
  • Body mass index 40 kg/m2 or less.
  • HbA1c 6.0% to 9.5% (42mmol/mol to 80mmol/mol) inclusive.

Exclusion Criteria:

  • Taking anti-diabetic therapies other than metformin
  • Pregnancy or women of childbearing age without adequate contraception
  • Women who are breastfeeding
  • Major psychiatric disease including diagnosed eating disorders, history of drug or alcohol abuse
  • Known sight-threatening retinopathy
  • Renal impairment (eGFR < 60 ml/min; CKD Stage 3)
  • Abnormal liver function tests (> 1.5 x upper limit of normal range)
  • Known ischaemic heart disease or heart failure
  • Known history of a stroke
  • Known history of porphyria
  • Concomitant use of miconazole or other oral antifungal medication.
  • Known or suspected allergy to trial product or related products
  • Oral steroid treatment 30 days prior to the start or at any time during the trial period.
  • Known malignancy or any other condition or circumstance which, in the opinion of the investigator, would affect the patient's ability to participate in the protocol.
  • Ketoacidosis
  • Felt to be unsuitable to participate in the trial in the opinion of the Chief Investigator.
  • Receipt of any investigational trial drug within 3 month prior to participation in the current trial.

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 ClinicalTrials.gov identifier (NCT number): NCT02830048


Locations
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United Kingdom
Clinical Research Unit, OCDEM, Churchill Hospital
Oxford, Oxfordshire, United Kingdom, OX3 7LE
Sponsors and Collaborators
University of Oxford
Oxford University Hospitals NHS Trust
Investigators
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Principal Investigator: Ioannis Spiliotis, MD University of Oxford

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Responsible Party: University of Oxford
ClinicalTrials.gov Identifier: NCT02830048    
Other Study ID Numbers: 19062015
2015-002837-23 ( EudraCT Number )
First Posted: July 12, 2016    Key Record Dates
Last Update Posted: May 31, 2017
Last Verified: May 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: The anonymised data (i.e. with studyID only) generated from this study will be deposited in the Oxford Research Archive (http://ora.ox.ac.uk/). This will provide a link between the results presented in publications and the underlying data. At the end of the retention period (currently 5 years), the data will be deleted from the archive.
Keywords provided by University of Oxford:
diabetes
glibenclamide
glucagon
Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Glyburide
Hypoglycemic Agents
Physiological Effects of Drugs