Epilepsy Clinical Trial
— iDENDOfficial title:
Impact of Timing of Initiation of Sulphonylurea Therapy on Neurodevelopmental Outcomes in Individuals With Intermediate Developmental Delay, Epilepsy and Neonatal Diabetes (iDEND) Syndrome Due to the V59M Mutation in the KCNJ11 Gene
NCT number | NCT05751525 |
Other study ID # | 120925 |
Secondary ID | |
Status | Recruiting |
Phase | |
First received | |
Last updated | |
Start date | July 1, 2016 |
Est. completion date | December 31, 2025 |
The goal of this observational study is to learn about the impact of the diabetes drug glibenclamide (glyburide) on neurodevelopment in individuals with iDEND (developmental delay, epilepsy and neonatal diabetes) due to the V59M mutation in the KCNJ11 gene. The main question it aims to answer is whether initiating sulphonylurea (SU) therapy in the first year of life results in better neurodevelopmental outcomes in affected individuals, in comparison to starting therapy later than 12 months of age. Participants will undergo a neurodevelopmental assessment comprising parental and teacher completion of standardised questionnaires, and where possible face to face neuropsychological testing. Researchers will compare the outcomes of these standardised tests in the individuals who started SU therapy <12 months of age in comparison to those who started >12 months of age.
Status | Recruiting |
Enrollment | 21 |
Est. completion date | December 31, 2025 |
Est. primary completion date | August 1, 2025 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 2 Years to 50 Years |
Eligibility | Inclusion Criteria: - Current age =2 years - Heterozygous for a V59M mutation in the KCNJ11 gene - Successfully transferred to oral sulphonylurea therapy - Willing to participate Exclusion Criteria: - Never able to transfer to oral sulphonylurea therapy - Unwilling to participate |
Country | Name | City | State |
---|---|---|---|
Italy | University of Rome | Rome | |
Norway | University of Bergen | Bergen | |
United Kingdom | University of Exeter | Exeter | |
United States | University of Chicago | Chicago | Illinois |
Lead Sponsor | Collaborator |
---|---|
Royal Devon and Exeter NHS Foundation Trust | University of Bergen, University of Chicago, University of Rome Tor Vergata |
United States, Italy, Norway, United Kingdom,
Beltrand J, Elie C, Busiah K, Fournier E, Boddaert N, Bahi-Buisson N, Vera M, Bui-Quoc E, Ingster-Moati I, Berdugo M, Simon A, Gozalo C, Djerada Z, Flechtner I, Treluyer JM, Scharfmann R, Cave H, Vaivre-Douret L, Polak M; GlidKir Study Group. Sulfonylurea Therapy Benefits Neurological and Psychomotor Functions in Patients With Neonatal Diabetes Owing to Potassium Channel Mutations. Diabetes Care. 2015 Nov;38(11):2033-41. doi: 10.2337/dc15-0837. Epub 2015 Oct 5. Erratum In: Diabetes Care. 2016 Jan;39(1):175. — View Citation
Bowman P, Broadbridge E, Knight BA, Pettit L, Flanagan SE, Reville M, Tonks J, Shepherd MH, Ford TJ, Hattersley AT. Psychiatric morbidity in children with KCNJ11 neonatal diabetes. Diabet Med. 2016 Oct;33(10):1387-91. doi: 10.1111/dme.13135. Epub 2016 May 21. — View Citation
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. Erratum In: Lancet Diabetes Endocrinol. 2018 Sep;6(9):e17. — View Citation
Clark RH, McTaggart JS, Webster R, Mannikko R, Iberl M, Sim XL, Rorsman P, Glitsch M, Beeson D, Ashcroft FM. Muscle dysfunction caused by a KATP channel mutation in neonatal diabetes is neuronal in origin. Science. 2010 Jul 23;329(5990):458-61. doi: 10.1126/science.1186146. Epub 2010 Jul 1. — View Citation
Fendler W, Pietrzak I, Brereton MF, Lahmann C, Gadzicki M, Bienkiewicz M, Drozdz I, Borowiec M, Malecki MT, Ashcroft FM, Mlynarski WM. Switching to sulphonylureas in children with iDEND syndrome caused by KCNJ11 mutations results in improved cerebellar perfusion. Diabetes Care. 2013 Aug;36(8):2311-6. doi: 10.2337/dc12-2166. Epub 2013 Mar 5. — View Citation
Flanagan SE, Edghill EL, Gloyn AL, Ellard S, Hattersley AT. Mutations in KCNJ11, which encodes Kir6.2, are a common cause of diabetes diagnosed in the first 6 months of life, with the phenotype determined by genotype. Diabetologia. 2006 Jun;49(6):1190-7. doi: 10.1007/s00125-006-0246-z. Epub 2006 Apr 12. — View Citation
Gloyn AL, Diatloff-Zito C, Edghill EL, Bellanne-Chantelot C, Nivot S, Coutant R, Ellard S, Hattersley AT, Robert JJ. KCNJ11 activating mutations are associated with developmental delay, epilepsy and neonatal diabetes syndrome and other neurological features. Eur J Hum Genet. 2006 Jul;14(7):824-30. doi: 10.1038/sj.ejhg.5201629. Epub 2006 May 3. — View Citation
Gloyn AL, Pearson ER, Antcliff JF, Proks P, Bruining GJ, Slingerland AS, Howard N, Srinivasan S, Silva JM, Molnes J, Edghill EL, Frayling TM, Temple IK, Mackay D, Shield JP, Sumnik Z, van Rhijn A, Wales JK, Clark P, Gorman S, Aisenberg J, Ellard S, Njolstad PR, Ashcroft FM, Hattersley AT. Activating mutations in the gene encoding the ATP-sensitive potassium-channel subunit Kir6.2 and permanent neonatal diabetes. N Engl J Med. 2004 Apr 29;350(18):1838-49. doi: 10.1056/NEJMoa032922. Erratum In: N Engl J Med. 2004 Sep 30;351(14):1470. — View Citation
Landmeier KA, Lanning M, Carmody D, Greeley SAW, Msall ME. ADHD, learning difficulties and sleep disturbances associated with KCNJ11-related neonatal diabetes. Pediatr Diabetes. 2017 Nov;18(7):518-523. doi: 10.1111/pedi.12428. Epub 2016 Aug 24. — View Citation
Mlynarski W, Tarasov AI, Gach A, Girard CA, Pietrzak I, Zubcevic L, Kusmierek J, Klupa T, Malecki MT, Ashcroft FM. Sulfonylurea improves CNS function in a case of intermediate DEND syndrome caused by a mutation in KCNJ11. Nat Clin Pract Neurol. 2007 Nov;3(11):640-5. doi: 10.1038/ncpneuro0640. — View Citation
Pearson ER, Flechtner I, Njolstad PR, Malecki MT, Flanagan SE, Larkin B, Ashcroft FM, Klimes I, Codner E, Iotova V, Slingerland AS, Shield J, Robert JJ, Holst JJ, Clark PM, Ellard S, Sovik O, Polak M, Hattersley AT; Neonatal Diabetes International Collaborative Group. Switching from insulin to oral sulfonylureas in patients with diabetes due to Kir6.2 mutations. N Engl J Med. 2006 Aug 3;355(5):467-77. doi: 10.1056/NEJMoa061759. — View Citation
Shah RP, Spruyt K, Kragie BC, Greeley SA, Msall ME. Visuomotor performance in KCNJ11-related neonatal diabetes is impaired in children with DEND-associated mutations and may be improved by early treatment with sulfonylureas. Diabetes Care. 2012 Oct;35(10):2086-8. doi: 10.2337/dc11-2225. Epub 2012 Aug 1. — View Citation
Slingerland AS, Hurkx W, Noordam K, Flanagan SE, Jukema JW, Meiners LC, Bruining GJ, Hattersley AT, Hadders-Algra M. Sulphonylurea therapy improves cognition in a patient with the V59M KCNJ11 mutation. Diabet Med. 2008 Mar;25(3):277-81. doi: 10.1111/j.1464-5491.2007.02373.x. — View Citation
Slingerland AS, Nuboer R, Hadders-Algra M, Hattersley AT, Bruining GJ. Improved motor development and good long-term glycaemic control with sulfonylurea treatment in a patient with the syndrome of intermediate developmental delay, early-onset generalised epilepsy and neonatal diabetes associated with the V59M mutation in the KCNJ11 gene. Diabetologia. 2006 Nov;49(11):2559-63. doi: 10.1007/s00125-006-0407-0. Epub 2006 Sep 19. — View Citation
Svalastoga P, Sulen A, Fehn JR, Aukland SM, Irgens H, Sirnes E, Fevang SKE, Valen E, Elgen IB, Njolstad PR. Intellectual Disability in KATP Channel Neonatal Diabetes. Diabetes Care. 2020 Mar;43(3):526-533. doi: 10.2337/dc19-1013. Epub 2020 Jan 13. — View Citation
* Note: There are 15 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Number and type of neurodevelopmental and psychiatric disorders | Measured by Development and Wellbeing Assessment (DAWBA) | At or up to 2 years after recruitment | |
Primary | Level of difficulty due to neurodevelopmental and psychiatric morbidity | Measured by Strengths and Difficulties Questionnaire (SDQ) total difficulties score. Scores range from 0-40 with higher scores indicating greater difficulties. Scores will be converted to Z-scores using normative population data for the purposes of analysis. | At or up to 2 years after recruitment | |
Primary | Impact on daily life | Measured by SDQ impact score. Scores range from 0-10 for parent and self-report and 0-6 for teacher report, with higher scores indicating greater difficulties. Scores will be converted to Z-scores using normative population data for the purposes of analysis. | At or up to 2 years after recruitment | |
Primary | IQ score | Measured by Leiter-3 International Performance Scale | Up to 3 years after recruitment | |
Secondary | Major milestones | Measured by parent report / review of clinical records | At or up to 2 years after recruitment | |
Secondary | Communication difficulties | Measured by the Children's Communication Checklist 2 (CCC-2) questionnaire, consisting of 70 items scored by parents / caregivers. Lower scores indicate more communication difficulties. | Up to 3 years after recruitment | |
Secondary | Hyperactivity, emotional problems, conduct problems, peer relationships, prosocial behaviour. | Measured by SDQ subsections. Scores range from 0-10 for each subsection with higher scores indicating greater difficulties, except prosocial score where lower scores indicate greater difficulties. Scores will be converted to Z-scores using normative population data for the purposes of analysis. | At or up to 2 years after recruitment |
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