The use of everolimus in the treatment of neurocognitive problems in tuberous sclerosis (TRON): study protocol for a randomised controlled trial

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dc.contributor.authorRandell, Elizabeth
dc.contributor.authorMcNamara, Rachel
dc.contributor.authorDavies, D Mark
dc.contributor.authorOwen-Jones, Eleri
dc.contributor.authorKirby, Nigel
dc.contributor.authorAngel, Lianna
dc.contributor.authorDrew, Cheney
dc.contributor.authorCannings-John, Rebecca
dc.contributor.authorSmalley, Michelle
dc.contributor.authorSaxena, Anurag
dc.contributor.authorMcDermott, Emer
dc.contributor.authorStockwell, Laura
dc.contributor.authorde Vries, Petrus J
dc.contributor.authorHood, Kerry
dc.contributor.authorSampson, Julian R
dc.date.accessioned2016-08-17T07:38:46Z
dc.date.available2016-08-17T07:38:46Z
dc.date.issued2016-08-11
dc.date.updated2016-08-11T18:02:05Z
dc.description.abstractBackground: Tuberous sclerosis complex (TSC) is a genetic disorder affecting about 1 in 6000 people and is characterised by the development of tumours in many organs, including the skin and kidneys, and by a range of neurological and neuropsychiatric manifestations. TSC-associated neuropsychiatric disorders (TAND) occur in the majority of those with TSC, and they have a significant impact on patients and their families, given the everyday impact of TAND on education, employment, family and social life. The potential benefits of better treatment for TAND therefore include reduction in health care demands and wider benefits for patients and their carers. Methods/design: We have planned a single-centre, two-arm, individually randomised, phase II, double-blind, placebo-controlled trial of everolimus versus placebo in the treatment of neurocognitive problems in patients with tuberous sclerosis. Everolimus is a licensed medicine in this patient group, but for a different target of effect. The present trial is a proof-of-principle study developed to provide effect size estimates which may be used to inform the design of subsequent trials. Forty-eight patients aged 16–60 years with tuberous sclerosis who have an IQ >60 and a significant deficit (at least −2 SD) in one or more primary outcome measures will be randomly allocated in a ratio of 2:1 to receive everolimus or placebo, respectively. Participants will be assessed for eligibility and then be started on study medication 4 weeks later. They will then be randomised and receive placebo or everolimus for 24 weeks. Neurocognitive and safety assessments will be carried out at baseline and weeks 4, 12, 24 and 36. Discussion: This study is designed to determine the effect sizes of treatment with everolimus or placebo for 6 months on specific neurocognitive functions—recall memory (verbal and non-verbal) and executive function—in people affected by TSC who have significant deficits in these functions. These data will provide new evidence to determine whether larger-scale trials are indicated and to explore suitable outcome measures and analytical methods for neurocognitive trial design.en_ZA
dc.identifier.apacitationRandell, E., McNamara, R., Davies, D. M., Owen-Jones, E., Kirby, N., Angel, L., ... Sampson, J. R. (2016). The use of everolimus in the treatment of neurocognitive problems in tuberous sclerosis (TRON): study protocol for a randomised controlled trial. <i>Trials</i>, http://hdl.handle.net/11427/21277en_ZA
dc.identifier.chicagocitationRandell, Elizabeth, Rachel McNamara, D Mark Davies, Eleri Owen-Jones, Nigel Kirby, Lianna Angel, Cheney Drew, et al "The use of everolimus in the treatment of neurocognitive problems in tuberous sclerosis (TRON): study protocol for a randomised controlled trial." <i>Trials</i> (2016) http://hdl.handle.net/11427/21277en_ZA
dc.identifier.citationRandell, E., McNamara, R., Davies, D. M., Owen-Jones, E., Kirby, N., Angel, L., ... & McDermott, E. (2016). The use of everolimus in the treatment of neurocognitive problems in tuberous sclerosis (TRON): study protocol for a randomised controlled trial. Trials, 17(1):39.en_ZA
dc.identifier.issn1745-6215en_ZA
dc.identifier.ris TY - Journal Article AU - Randell, Elizabeth AU - McNamara, Rachel AU - Davies, D Mark AU - Owen-Jones, Eleri AU - Kirby, Nigel AU - Angel, Lianna AU - Drew, Cheney AU - Cannings-John, Rebecca AU - Smalley, Michelle AU - Saxena, Anurag AU - McDermott, Emer AU - Stockwell, Laura AU - de Vries, Petrus J AU - Hood, Kerry AU - Sampson, Julian R AB - Background: Tuberous sclerosis complex (TSC) is a genetic disorder affecting about 1 in 6000 people and is characterised by the development of tumours in many organs, including the skin and kidneys, and by a range of neurological and neuropsychiatric manifestations. TSC-associated neuropsychiatric disorders (TAND) occur in the majority of those with TSC, and they have a significant impact on patients and their families, given the everyday impact of TAND on education, employment, family and social life. The potential benefits of better treatment for TAND therefore include reduction in health care demands and wider benefits for patients and their carers. Methods/design: We have planned a single-centre, two-arm, individually randomised, phase II, double-blind, placebo-controlled trial of everolimus versus placebo in the treatment of neurocognitive problems in patients with tuberous sclerosis. Everolimus is a licensed medicine in this patient group, but for a different target of effect. The present trial is a proof-of-principle study developed to provide effect size estimates which may be used to inform the design of subsequent trials. Forty-eight patients aged 16–60 years with tuberous sclerosis who have an IQ >60 and a significant deficit (at least −2 SD) in one or more primary outcome measures will be randomly allocated in a ratio of 2:1 to receive everolimus or placebo, respectively. Participants will be assessed for eligibility and then be started on study medication 4 weeks later. They will then be randomised and receive placebo or everolimus for 24 weeks. Neurocognitive and safety assessments will be carried out at baseline and weeks 4, 12, 24 and 36. Discussion: This study is designed to determine the effect sizes of treatment with everolimus or placebo for 6 months on specific neurocognitive functions—recall memory (verbal and non-verbal) and executive function—in people affected by TSC who have significant deficits in these functions. These data will provide new evidence to determine whether larger-scale trials are indicated and to explore suitable outcome measures and analytical methods for neurocognitive trial design. DA - 2016-08-11 DB - OpenUCT DO - 10.1186/s13063-016-1446-6 DP - University of Cape Town J1 - Trials LK - https://open.uct.ac.za PB - University of Cape Town PY - 2016 SM - 1745-6215 T1 - The use of everolimus in the treatment of neurocognitive problems in tuberous sclerosis (TRON): study protocol for a randomised controlled trial TI - The use of everolimus in the treatment of neurocognitive problems in tuberous sclerosis (TRON): study protocol for a randomised controlled trial UR - http://hdl.handle.net/11427/21277 ER - en_ZA
dc.identifier.urihttp://dx.doi.org/10.1186/s13063-016-1446-6
dc.identifier.urihttp://hdl.handle.net/11427/21277
dc.identifier.vancouvercitationRandell E, McNamara R, Davies DM, Owen-Jones E, Kirby N, Angel L, et al. The use of everolimus in the treatment of neurocognitive problems in tuberous sclerosis (TRON): study protocol for a randomised controlled trial. Trials. 2016; http://hdl.handle.net/11427/21277.en_ZA
dc.languageengen_ZA
dc.language.rfc3066en
dc.publisherBioMed Centralen_ZA
dc.publisher.departmentDepartment of Psychiatry and Mental Healthen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsCreative Commons Attribution 4.0 International (CC BY 4.0)*
dc.rights.holderRandell et al.
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_ZA
dc.sourceTrialsen_ZA
dc.source.urihttps://trialsjournal.biomedcentral.com/
dc.titleThe use of everolimus in the treatment of neurocognitive problems in tuberous sclerosis (TRON): study protocol for a randomised controlled trialen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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