Low dosE GlibENclamide in Diabetes Part A

NCT02830048 | Completed Phase 2 DMC

• 2 other identifiers: 190620152015-002837-23
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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.

Conditions

Diabetes Mellitus, Type 2

Keywords

diabetes; glibenclamide; glucagon

Outcome Measures

Primary Outcomes (1)

• Decrease in fasting plasma glucagon concentration

  Concentration of plasma glucagon using fasting blood samples prior to each dose change.

  After 3-4 days of treatment at each dose increment

Secondary Outcomes (3)

• Overall improvement in glycaemic control throughout the day

  After 3-4 days of treatment at each dose increment

• Effect on fasting glucose, insulin and C-peptide levels

  After 3-4 days of treatment at each dose increment

• Pre-dose plasma concentration of glibenclamide

  After 3-4 days of treatment at each dose increment

Study Arms (1)

Glibenclamide dose titration

EXPERIMENTAL

Increasing doses of glibenclamide oral suspension from 0.3mg/day to 6mg/day.

Drug: Glibenclamide

Interventions

Glibenclamide DRUG

Also known as: GlibenTek

Glibenclamide dose titration

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Oxford: lead
• Oxford University Hospitals NHS Trust: collaborator

Study Sites (1)

Clinical Research Unit, OCDEM, Churchill Hospital

Oxford, Oxfordshire, OX3 7LE, United Kingdom

Location

Related Publications (1)

• Spiliotis II, Chalk R, Gough S, Rorsman P. Reducing hyperglucagonaemia in type 2 diabetes using low-dose glibenclamide: Results of the LEGEND-A pilot study. Diabetes Obes Metab. 2022 Aug;24(8):1671-1675. doi: 10.1111/dom.14740. Epub 2022 May 18. No abstract available.

  PMID: 35491519 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Diabetes Mellitus

Interventions

Glyburide

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Sulfonylurea Compounds; Urea; Amides; Organic Chemicals; Sulfones; Sulfur Compounds

Study Officials

• Ioannis Spiliotis, MD

  University of Oxford

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2016
• First Posted: July 12, 2016
• Study Start: July 1, 2016
• Primary Completion: March 9, 2017
• Study Completion: March 9, 2017
• Last Updated: May 31, 2017

Record last verified: 2017-05

Data Sharing

• IPD Sharing: Will share

Locations

GB (1)