Switching From Insulin to Sulfonylurea in Diabetes Associated With Variants in MODY Genes

NCT04239586 | Unknown Phase 4

• 1 other identifier: 2018/2388
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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).

Conditions

Maturity-Onset Diabetes of the Young, Type 3; Maturity Onset Diabetes of the Young, Type 1; Childhood Diabetes Mellitus; Insulin-dependent Diabetes Mellitus

Keywords

Maturity onset diabetes in the young; Childhood diabetes; Type 1 diabetes

Outcome Measures

Primary Outcomes (2)

• Effect of sulfonylurea treatment on insulin requirement measured in units insulin per kg per day

  Effect of sulfonylurea treatment on insulin requirement measured in units insulin per kg bodyweight per day, recorded at intervals of 3-6 months after exposure to sulfonylurea compared to before initiation of sulfonylurea

  5 years

• Metabolic control of diabetes measured by HbA1c in mmol/mol

  Metabolic control of diabetes measured by HbA1c in mmol/mol, recorded at intervals of 3-6 months after exposure to sulfonylurea compared to before initiation of sulfonylurea

  5 years

Secondary Outcomes (4)

• Level of sulfonylurea dose in mg per kg per day

  5 years

• Prevalence of side effects of sulfonylurea

  5 years

• Effect on endogenous insulin secretion assessed by intravenous glucose tolerance tests

  5 years

• Effect on secretion of incretin hormones, assessed by oral glucose tolerance tests

  5 years

Study Arms (1)

Sulfonylurea treatment group

EXPERIMENTAL

Increasing doses of sulfonylurea class of drug to see whether insulin treatment can be reduced in dose or stopped.

Drug: Sulfonylurea

Interventions

Sulfonylurea DRUG

Starting treatment with sulfonylurea class of drug

Also known as: Glibenclamide, Glipizide, Glimerepiride

Sulfonylurea treatment group

Eligibility Criteria

• Age: 2 Years - 95 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Diabetes and DNA sequence variant of unknown significance (VUS, class 3) or pathogenic (class 4, and 5) in the HNF1A, HNF4A, or HNF1B genes
• On insulin treatment
• Willing and able to provide informed consent (parents if younger than 16 years of age)

You may not qualify if:

• Known anaphylactic response to sulfonylurea
• Diabetes and DNA sequence variant in the HNF1A, HNF4A, or HNF1B genes that are known to be non-pathogenic (class 1-2)
• Not willing or able to provide informed consent (parents if younger than 16 years of age)

Sponsors & Collaborators

• Haukeland University Hospital: lead

Study Sites (1)

Department of Pediatrics and Adolescents, Haukeland University Hospital, and Department of Clinical Science, Faculty of Medicine, University of Bergen

Bergen, NO-5021, Norway

Location

Related Publications (17)

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  PMID: 15115830 BACKGROUND

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  PMID: 16885550 BACKGROUND

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• Babenko AP, Polak M, Cave H, Busiah K, Czernichow P, Scharfmann R, Bryan J, Aguilar-Bryan L, Vaxillaire M, Froguel P. Activating mutations in the ABCC8 gene in neonatal diabetes mellitus. N Engl J Med. 2006 Aug 3;355(5):456-66. doi: 10.1056/NEJMoa055068.

  PMID: 16885549 BACKGROUND

• Johansson BB, Irgens HU, Molnes J, Sztromwasser P, Aukrust I, Juliusson PB, Sovik O, Levy S, Skrivarhaug T, Joner G, Molven A, Johansson S, Njolstad PR. Targeted next-generation sequencing reveals MODY in up to 6.5% of antibody-negative diabetes cases listed in the Norwegian Childhood Diabetes Registry. Diabetologia. 2017 Apr;60(4):625-635. doi: 10.1007/s00125-016-4167-1. Epub 2016 Dec 2.

  PMID: 27913849 BACKGROUND

• Irgens HU, Molnes J, Johansson BB, Ringdal M, Skrivarhaug T, Undlien DE, Sovik O, Joner G, Molven A, Njolstad PR. Prevalence of monogenic diabetes in the population-based Norwegian Childhood Diabetes Registry. Diabetologia. 2013 Jul;56(7):1512-9. doi: 10.1007/s00125-013-2916-y. Epub 2013 Apr 27.

  PMID: 23624530 BACKGROUND

• Najmi LA, Aukrust I, Flannick J, Molnes J, Burtt N, Molven A, Groop L, Altshuler D, Johansson S, Bjorkhaug L, Njolstad PR. Functional Investigations of HNF1A Identify Rare Variants as Risk Factors for Type 2 Diabetes in the General Population. Diabetes. 2017 Feb;66(2):335-346. doi: 10.2337/db16-0460. Epub 2016 Nov 29.

  PMID: 27899486 BACKGROUND

• Hattersley AT, Greeley SAW, Polak M, Rubio-Cabezas O, Njolstad PR, Mlynarski W, Castano L, Carlsson A, Raile K, Chi DV, Ellard S, Craig ME. ISPAD Clinical Practice Consensus Guidelines 2018: The diagnosis and management of monogenic diabetes in children and adolescents. Pediatr Diabetes. 2018 Oct;19 Suppl 27:47-63. doi: 10.1111/pedi.12772. No abstract available.

  PMID: 30225972 BACKGROUND

• Bowman P, Sulen A, Barbetti F, Beltrand J, Svalastoga P, Codner E, Tessmann EH, Juliusson PB, Skrivarhaug T, Pearson ER, Flanagan SE, Babiker T, Thomas NJ, Shepherd MH, Ellard S, Klimes I, Szopa M, Polak M, Iafusco D, Hattersley AT, Njolstad PR; Neonatal Diabetes International Collaborative Group. Effectiveness and safety of long-term treatment with sulfonylureas in patients with neonatal diabetes due to KCNJ11 mutations: an international cohort study. Lancet Diabetes Endocrinol. 2018 Aug;6(8):637-646. doi: 10.1016/S2213-8587(18)30106-2. Epub 2018 Jun 4.

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• Balamurugan K, Bjorkhaug L, Mahajan S, Kanthimathi S, Njolstad PR, Srinivasan N, Mohan V, Radha V. Structure-function studies of HNF1A (MODY3) gene mutations in South Indian patients with monogenic diabetes. Clin Genet. 2016 Dec;90(6):486-495. doi: 10.1111/cge.12757. Epub 2016 Mar 4.

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  PMID: 24097065 BACKGROUND

• Svalastoga P, Kaci A, Molnes J, Solheim MH, Johansson BB, Krogvold L, Skrivarhaug T, Valen E, Johansson S, Molven A, Sagen JV, Softeland E, Bjorkhaug L, Tjora E, Aukrust I, Njolstad PR. Characterisation of HNF1A variants in paediatric diabetes in Norway using functional and clinical investigations to unmask phenotype and monogenic diabetes. Diabetologia. 2023 Dec;66(12):2226-2237. doi: 10.1007/s00125-023-06012-4. Epub 2023 Oct 5.

  PMID: 37798422 DERIVED

MeSH Terms

Conditions

Maturity-Onset Diabetes of the Young, Type 3; Maturity-Onset Diabetes of the Young, Type 1; Diabetes Mellitus, Type 1

Interventions

Sulfonylurea Compounds; Glyburide; Glipizide

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Urea; Amides; Organic Chemicals; Sulfones; Sulfur Compounds

Study Officials

• Pål R. Njølstad, MD, PhD

  Haukeland University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Switching insulin-treated diabetes patients with possibly disease causing mutations in HNF1A, HNF4A, or HNF1B to treatment with sulfonylurea.

Study Record Dates

• First Submitted: January 2, 2020
• First Posted: January 27, 2020
• Study Start: April 18, 2017
• Primary Completion: April 1, 2022
• Study Completion: April 1, 2022
• Last Updated: January 27, 2020

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: 6 months after the planned publications are finally accepted for publication.
• Access Criteria: IPD will be shared after written request and consideration to the corresponding author of the respective publication. Data will be shared with researchers in the same or similar field only. IPD will include summary data without personal identity and Describe by what access criteria IPD and any additional supporting information will be shared, including with whom, for what types of analyses, and by what mechanism. The corresponding and first authors will review requests and criteria for reviewing requests may also be provided.

Locations

NO (1)