Ignite Creation Date:
2024-05-06 @ 2:11 PM
Last Modification Date:
2024-10-26 @ 1:26 PM
Study NCT ID:
NCT04239586
Status:
UNKNOWN
Last Update Posted:
2020-01-27
First Post:
2020-01-02
Brief Title:
Switching From Insulin to Sulfonylurea in Diabetes Associated With Variants in MODY Genes
Sponsor:
Haukeland University Hospital
Organization:
Haukeland University Hospital
Study Overview
Official Title:
Switching From Insulin to Sulfonylurea in Childhood and Adult Diabetes Due to Variants in the HNF1A HNF4A or HNF1B Genes
Status:
UNKNOWN
Status Verified Date:
2020-01
Last Known Status:
ENROLLING_BY_INVITATION
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
SUtoChildT1D
Brief Summary:
The purpose of this study is to switch from insulin to oral sulfonylurea in patients with apparent type 1 diabetes or maturity onset diabetes in the young that are insulin treated The molecular cause will be DNA variants in the HNF1A HNF4A or HNF1B genes that are of unknown significance VUS class 3 or known to be pathogenic class 4 and 5
Detailed Description:
Maturity onset diabetes in the young MODY is characterised by monogenic diabetes due to beta-cell dysfunction with typical onset of diabetes before age of 25 years There are 14 known forms of MODY ranging from rather common to extremely rare
About 1 of patients in the Norwegian Childhood Diabetes registry may have disease causing MODY mutations according to a study recently published by the investigators group and others
MODY associated mutations in the transcription factors HNF1A HNF4A and HNF1B leads to activation of the potassium channel causing depolarisation of the beta-cell membrane which is crucial for excretion of insulin By treating patients with HNF1A-MODY HNF4A-MODY and HNF1B-MODY with sulfonylurea class of drugs these channels will close causing depolarisation of the beta-cell membrane and release of insulin Hence these patients can often stop insulin treatment when they are treated with sulfonylurea class drugs
Due to high throughput sequencing a number of rare variants in these genes have been discovered In many cases bioinformatic tools are not sufficient to correctly classify these variants In the present study we intend to identify rare variants in the HNF1A HNF4A and HNF1B genes in patients with insulin dependent diabetes identified through the Norwegian Childhood Diabetes registry or the Norwegian MODY Registry with possibly disease causing HNF1A HNF4A or HNF1B mutations with sulfonylurea to see if they can reduce or even stop insulin treatment and regulate their diabetes with sulfonylurea only All variants will be investigated by bioinformatics tools as well as functional assays tests for DNA-binding transcriptional activation nuclear localisation protein expression Primary endpoints are efficacy of sulfonylurea treatment measured by insulin requirement or not and level of HbA1c Secondary endpoints are tolerance of sulfonylurea and effect on insulin secretion by oral and intravenous glucose tolerance tests Bioinformatics and functional characterisation will be compared with success to reach primary endpoints
About 1 of patients in the Norwegian Childhood Diabetes registry may have disease causing MODY mutations according to a study recently published by the investigators group and others
MODY associated mutations in the transcription factors HNF1A HNF4A and HNF1B leads to activation of the potassium channel causing depolarisation of the beta-cell membrane which is crucial for excretion of insulin By treating patients with HNF1A-MODY HNF4A-MODY and HNF1B-MODY with sulfonylurea class of drugs these channels will close causing depolarisation of the beta-cell membrane and release of insulin Hence these patients can often stop insulin treatment when they are treated with sulfonylurea class drugs
Due to high throughput sequencing a number of rare variants in these genes have been discovered In many cases bioinformatic tools are not sufficient to correctly classify these variants In the present study we intend to identify rare variants in the HNF1A HNF4A and HNF1B genes in patients with insulin dependent diabetes identified through the Norwegian Childhood Diabetes registry or the Norwegian MODY Registry with possibly disease causing HNF1A HNF4A or HNF1B mutations with sulfonylurea to see if they can reduce or even stop insulin treatment and regulate their diabetes with sulfonylurea only All variants will be investigated by bioinformatics tools as well as functional assays tests for DNA-binding transcriptional activation nuclear localisation protein expression Primary endpoints are efficacy of sulfonylurea treatment measured by insulin requirement or not and level of HbA1c Secondary endpoints are tolerance of sulfonylurea and effect on insulin secretion by oral and intravenous glucose tolerance tests Bioinformatics and functional characterisation will be compared with success to reach primary endpoints
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None