Efficacy and Safety Study of Sulfonylureas in Neonatal Diabetes Mellitus (GLIDKIR6-2)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT00610038
First received: January 24, 2008
Last updated: November 16, 2012
Last verified: November 2012
  Purpose

The aim of our trial is to try to switch patients with permanent neonatal diabetes mellitus due to a Kir6.2 or SUR1 activating mutation from subcutaneous insulin to oral glibenclamide therapy.


Condition Intervention Phase
Diabetes Mellitus
Drug: glibenclamide
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Sulfonylureas in Neonatal Diabetes Mellitus With Mutations of 2 Type of Subunits Kir6.2 and SUR1 of the Pancreatic Beta-cell ATP-sensitive K+ Channel.

Resource links provided by NLM:


Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • assess continuously the capillary glycaemia for three consecutive days and evaluate the insulin secretion under insulin and sulfonylureas [ Time Frame: permanent ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Rate the neurological and developmental status of the patients to seek for a potential improvement under glibenclamide therapy [ Time Frame: every year ] [ Designated as safety issue: Yes ]
  • To assess the kinetics of glibenclamide in children [ Time Frame: at the end of study ] [ Designated as safety issue: Yes ]

Enrollment: 19
Study Start Date: July 2006
Study Completion Date: December 2011
Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Glibenclamide
Drug: glibenclamide
Switching the patients from subcutaneous insulin to oral glibenclamide therapy
Other Name: Sulfonylureas

Detailed Description:

Neonatal diabetes mellitus, characterized by hyperglycaemia requiring exogenous insulin therapy appearing during the first months of life, is a rare condition with an estimated incidence of 1 in 400000 newborns and is permanent in only one-half of the patients[1]. Several studies have identified heterozygous activating mutations of the coding sequence of KCNJ11 or ABCC8 in patients having a permanent neonatal diabetes mellitus [5,6,7,8]. These genes encode for the 2 type of subunits Kir6.2 or SUR1 of the pancreatic β-cell ATP-sensitive K+ channel (KATP channel) which plays a central role in glucose-stimulating insulin secretion. These channels are also found on muscle and nervous cells, and this may explain the neurological features sometimes associated with permanent neonatal diabetes mellitus. Some sulfonylureas, as the glibenclamide, stimulate insulin secretion by binding to SUR1 subunit and closing KATP channels by an ATP-independent mechanism. The glibenclamide is used efficiently in type 2 diabetes but also recently in replacement of subcutaneous injected insulin in children with a Kir6.2 or SUR1 activating mutation [7,8,11-13].

The aim of our trial is to try to switch patients with permanent neonatal diabetes mellitus due to a Kir6.2 or SUR1 activating mutation from subcutaneous insulin to oral glibenclamide therapy. This study will stand at Necker-Enfants Malades Hospital in the Endocrinology and Diabetology Unit of the Professors Robert and POLAK. It will include 20 patients, most of them already identified. This study has two purposes: therapeutic by switching the patients from subcutaneous insulin to oral glibenclamide therapy, and cognitive by a complementary evaluation and understanding of the mechanisms of insulin secretion and of glibenclamide efficiency. To do so, we will assess continuously the capillary glycaemia for three consecutive days and evaluate the insulin secretion under insulin and sulfonylureas. Furthermore, we will rate the neurological and developmental status of the patients to seek for a potential improvement under glibenclamide therapy.

If oral glibenclamide therapy for these patients is proved to be successful, the systematic search for a Kir6.2 or SUR1 activating heterozygous mutation in newborns with permanent neonatal diabetes mellitus could be recommended in order to start early oral glibenclamide therapy and thus extend the indications for the sulfonylureas.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • coding sequence of KCNJ11 or ABCC8 in patients having a permanent neonatal diabetes mellitus
  • written informed consent

Exclusion Criteria:

  • hypersensibility of sulfonylureas
  • severe renal failure (clearance of creatinemia < 30 ml/min)
  • severe hepatic failure (Prothrombin rate < 70 %)
  • Porphyria
  • imidazol treatments
  • pregnancy
  • no social security affiliation
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00610038

Locations
France
Necker Hospital - Endocrinology Gynecology Pediatric unit
Paris, France, 75015
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
Principal Investigator: Michel Polak, MD, PhD Necker Hospital AP-HP
  More Information

No publications provided

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT00610038     History of Changes
Other Study ID Numbers: P050702
Study First Received: January 24, 2008
Last Updated: November 16, 2012
Health Authority: France: Ministry of Health

Keywords provided by Assistance Publique - Hôpitaux de Paris:
neonatal
diabetes mellitus
mutation
KIR6.2
SUR1
Neonatal diabetes mellitus with KIR6.2 or SUR1 mutations

Additional relevant MeSH terms:
Diabetes Mellitus
Infant, Newborn, Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Glyburide
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 26, 2014