Randomized placebo-controlled study of lovastatin in children with neurofibromatosis type 1

Jonathan M. Payne; Belinda Barton; Nicole J. Ullrich; Alan Cantor; Stephen J C Hearps; Gary Cutter; Tena Rosser; Karin S. Walsh; Gerard A. Gioia; Pamela L. Wolters; James Tonsgard; Elizabeth Schorry; David Viskochil; Laura Klesse; Michael Fisher; David H. Gutmann; Alcino J. Silva; Scott J. Hunter; Celiane Rey-Casserly; Nancy L. Cantor; Anna W. Byars; Peter L. Stavinoha; Joseph D. Ackerson; Carol L. Armstrong; Jill Isenberg; Sharon H. O'Neil; Roger J. Packer; Bruce Korf; Maria T. Acosta; Kathryn N. North

doi:10.1212/WNL.0000000000003435

Randomized placebo-controlled study of lovastatin in children with neurofibromatosis type 1

Jonathan M. Payne, Belinda Barton, Nicole J. Ullrich, Alan Cantor, Stephen J C Hearps, Gary Cutter, Tena Rosser, Karin S. Walsh, Gerard A. Gioia, Pamela L. Wolters, James Tonsgard, Elizabeth Schorry, David Viskochil, Laura Klesse, Michael Fisher, David H. Gutmann, Alcino J. Silva, Scott J. Hunter, Celiane Rey-Casserly, Nancy L. CantorAnna W. Byars, Peter L. Stavinoha, Joseph D. Ackerson, Carol L. Armstrong, Jill Isenberg, Sharon H. O'Neil, Roger J. Packer, Bruce Korf, Maria T. Acosta, Kathryn N. North

Research output: Contribution to journal › Article › peer-review

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Abstract

Objective: To assess the efficacy of lovastatin on visuospatial learning and attention for treating cognitive and behavioral deficits in children with neurofibromatosis type 1 (NF1). Methods: A multicenter, international, randomized, double-blind, placebo-controlled trial was conducted between July 2009 and May 2014 as part of the NF Clinical Trials Consortium. Children with NF1 aged 8-15 years were screened for visuospatial learning or attention deficits (n = 272); 146 children demonstrated deficits at baseline and were randomly assigned to lovastatin (n = 74; 40 mg/d) or placebo (n = 70). Treatment was administered once daily for 16 weeks. Primary outcomes were total errors on the Cambridge Neuropsychological Test Automated Battery Paired Associate Learning task (visuospatial learning) and the Score subtest from the Test of Everyday Attention for Children (sustained attention). Secondary outcomes measured executive function, attention, visuospatial skills, behavior, and quality of life. Primary analyses were performed on the intention-to-treat population. Results: Lovastatin had no significant effect on primary outcomes after 16 weeks of treatment: visuospatial learning (Cohen d = -0.15, 95% confidence interval -0.47 to 0.18) or sustained attention (Cohen d = 0.19, 95% confidence interval -0.14 to 0.53). Lovastatin was well tolerated, with no increase in reported adverse events compared to placebo. Conclusions: Lovastatin administered once daily for 16 weeks did not improve visuospatial learning or attention in children with NF1 and is not recommended for amelioration of cognitive deficits in this population. ClinicalTrials.gov identifier: This study was registered at ClinicalTrials.gov (NCT00853580) and Australian New Zealand Clinical Trials Registry (ACTRN12607000560493). Classification of evidence: This study provides Class I evidence that for children with NF1, lovastatin does not improve visuospatial learning or attention deficits.

Original language	English (US)
Pages (from-to)	2575-2584
Number of pages	10
Journal	Neurology
Volume	87
Issue number	24
DOIs	https://doi.org/10.1212/WNL.0000000000003435
State	Published - Dec 13 2016

ASJC Scopus subject areas

Clinical Neurology

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Payne, J. M., Barton, B., Ullrich, N. J., Cantor, A., Hearps, S. J. C., Cutter, G., Rosser, T., Walsh, K. S., Gioia, G. A., Wolters, P. L., Tonsgard, J., Schorry, E., Viskochil, D., Klesse, L., Fisher, M., Gutmann, D. H., Silva, A. J., Hunter, S. J., Rey-Casserly, C., ... North, K. N. (2016). Randomized placebo-controlled study of lovastatin in children with neurofibromatosis type 1. Neurology, 87(24), 2575-2584. https://doi.org/10.1212/WNL.0000000000003435

Payne, JM, Barton, B, Ullrich, NJ, Cantor, A, Hearps, SJC, Cutter, G, Rosser, T, Walsh, KS, Gioia, GA, Wolters, PL, Tonsgard, J, Schorry, E, Viskochil, D, Klesse, L, Fisher, M, Gutmann, DH, Silva, AJ, Hunter, SJ, Rey-Casserly, C, Cantor, NL, Byars, AW, Stavinoha, PL, Ackerson, JD, Armstrong, CL, Isenberg, J, O'Neil, SH, Packer, RJ, Korf, B, Acosta, MT & North, KN 2016, 'Randomized placebo-controlled study of lovastatin in children with neurofibromatosis type 1', Neurology, vol. 87, no. 24, pp. 2575-2584. https://doi.org/10.1212/WNL.0000000000003435

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title = "Randomized placebo-controlled study of lovastatin in children with neurofibromatosis type 1",

abstract = "Objective: To assess the efficacy of lovastatin on visuospatial learning and attention for treating cognitive and behavioral deficits in children with neurofibromatosis type 1 (NF1). Methods: A multicenter, international, randomized, double-blind, placebo-controlled trial was conducted between July 2009 and May 2014 as part of the NF Clinical Trials Consortium. Children with NF1 aged 8-15 years were screened for visuospatial learning or attention deficits (n = 272); 146 children demonstrated deficits at baseline and were randomly assigned to lovastatin (n = 74; 40 mg/d) or placebo (n = 70). Treatment was administered once daily for 16 weeks. Primary outcomes were total errors on the Cambridge Neuropsychological Test Automated Battery Paired Associate Learning task (visuospatial learning) and the Score subtest from the Test of Everyday Attention for Children (sustained attention). Secondary outcomes measured executive function, attention, visuospatial skills, behavior, and quality of life. Primary analyses were performed on the intention-to-treat population. Results: Lovastatin had no significant effect on primary outcomes after 16 weeks of treatment: visuospatial learning (Cohen d = -0.15, 95% confidence interval -0.47 to 0.18) or sustained attention (Cohen d = 0.19, 95% confidence interval -0.14 to 0.53). Lovastatin was well tolerated, with no increase in reported adverse events compared to placebo. Conclusions: Lovastatin administered once daily for 16 weeks did not improve visuospatial learning or attention in children with NF1 and is not recommended for amelioration of cognitive deficits in this population. ClinicalTrials.gov identifier: This study was registered at ClinicalTrials.gov (NCT00853580) and Australian New Zealand Clinical Trials Registry (ACTRN12607000560493). Classification of evidence: This study provides Class I evidence that for children with NF1, lovastatin does not improve visuospatial learning or attention deficits.",

author = "Payne, {Jonathan M.} and Belinda Barton and Ullrich, {Nicole J.} and Alan Cantor and Hearps, {Stephen J C} and Gary Cutter and Tena Rosser and Walsh, {Karin S.} and Gioia, {Gerard A.} and Wolters, {Pamela L.} and James Tonsgard and Elizabeth Schorry and David Viskochil and Laura Klesse and Michael Fisher and Gutmann, {David H.} and Silva, {Alcino J.} and Hunter, {Scott J.} and Celiane Rey-Casserly and Cantor, {Nancy L.} and Byars, {Anna W.} and Stavinoha, {Peter L.} and Ackerson, {Joseph D.} and Armstrong, {Carol L.} and Jill Isenberg and O'Neil, {Sharon H.} and Packer, {Roger J.} and Bruce Korf and Acosta, {Maria T.} and North, {Kathryn N.}",

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year = "2016",

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doi = "10.1212/WNL.0000000000003435",

language = "English (US)",

volume = "87",

pages = "2575--2584",

journal = "Neurology",

issn = "0028-3878",

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number = "24",

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TY - JOUR

T1 - Randomized placebo-controlled study of lovastatin in children with neurofibromatosis type 1

AU - Payne, Jonathan M.

AU - Barton, Belinda

AU - Ullrich, Nicole J.

AU - Cantor, Alan

AU - Hearps, Stephen J C

AU - Cutter, Gary

AU - Rosser, Tena

AU - Walsh, Karin S.

AU - Gioia, Gerard A.

AU - Wolters, Pamela L.

AU - Tonsgard, James

AU - Schorry, Elizabeth

AU - Viskochil, David

AU - Klesse, Laura

AU - Fisher, Michael

AU - Gutmann, David H.

AU - Silva, Alcino J.

AU - Hunter, Scott J.

AU - Rey-Casserly, Celiane

AU - Cantor, Nancy L.

AU - Byars, Anna W.

AU - Stavinoha, Peter L.

AU - Ackerson, Joseph D.

AU - Armstrong, Carol L.

AU - Isenberg, Jill

AU - O'Neil, Sharon H.

AU - Packer, Roger J.

AU - Korf, Bruce

AU - Acosta, Maria T.

AU - North, Kathryn N.

PY - 2016/12/13

Y1 - 2016/12/13

N2 - Objective: To assess the efficacy of lovastatin on visuospatial learning and attention for treating cognitive and behavioral deficits in children with neurofibromatosis type 1 (NF1). Methods: A multicenter, international, randomized, double-blind, placebo-controlled trial was conducted between July 2009 and May 2014 as part of the NF Clinical Trials Consortium. Children with NF1 aged 8-15 years were screened for visuospatial learning or attention deficits (n = 272); 146 children demonstrated deficits at baseline and were randomly assigned to lovastatin (n = 74; 40 mg/d) or placebo (n = 70). Treatment was administered once daily for 16 weeks. Primary outcomes were total errors on the Cambridge Neuropsychological Test Automated Battery Paired Associate Learning task (visuospatial learning) and the Score subtest from the Test of Everyday Attention for Children (sustained attention). Secondary outcomes measured executive function, attention, visuospatial skills, behavior, and quality of life. Primary analyses were performed on the intention-to-treat population. Results: Lovastatin had no significant effect on primary outcomes after 16 weeks of treatment: visuospatial learning (Cohen d = -0.15, 95% confidence interval -0.47 to 0.18) or sustained attention (Cohen d = 0.19, 95% confidence interval -0.14 to 0.53). Lovastatin was well tolerated, with no increase in reported adverse events compared to placebo. Conclusions: Lovastatin administered once daily for 16 weeks did not improve visuospatial learning or attention in children with NF1 and is not recommended for amelioration of cognitive deficits in this population. ClinicalTrials.gov identifier: This study was registered at ClinicalTrials.gov (NCT00853580) and Australian New Zealand Clinical Trials Registry (ACTRN12607000560493). Classification of evidence: This study provides Class I evidence that for children with NF1, lovastatin does not improve visuospatial learning or attention deficits.

AB - Objective: To assess the efficacy of lovastatin on visuospatial learning and attention for treating cognitive and behavioral deficits in children with neurofibromatosis type 1 (NF1). Methods: A multicenter, international, randomized, double-blind, placebo-controlled trial was conducted between July 2009 and May 2014 as part of the NF Clinical Trials Consortium. Children with NF1 aged 8-15 years were screened for visuospatial learning or attention deficits (n = 272); 146 children demonstrated deficits at baseline and were randomly assigned to lovastatin (n = 74; 40 mg/d) or placebo (n = 70). Treatment was administered once daily for 16 weeks. Primary outcomes were total errors on the Cambridge Neuropsychological Test Automated Battery Paired Associate Learning task (visuospatial learning) and the Score subtest from the Test of Everyday Attention for Children (sustained attention). Secondary outcomes measured executive function, attention, visuospatial skills, behavior, and quality of life. Primary analyses were performed on the intention-to-treat population. Results: Lovastatin had no significant effect on primary outcomes after 16 weeks of treatment: visuospatial learning (Cohen d = -0.15, 95% confidence interval -0.47 to 0.18) or sustained attention (Cohen d = 0.19, 95% confidence interval -0.14 to 0.53). Lovastatin was well tolerated, with no increase in reported adverse events compared to placebo. Conclusions: Lovastatin administered once daily for 16 weeks did not improve visuospatial learning or attention in children with NF1 and is not recommended for amelioration of cognitive deficits in this population. ClinicalTrials.gov identifier: This study was registered at ClinicalTrials.gov (NCT00853580) and Australian New Zealand Clinical Trials Registry (ACTRN12607000560493). Classification of evidence: This study provides Class I evidence that for children with NF1, lovastatin does not improve visuospatial learning or attention deficits.

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ER -

Randomized placebo-controlled study of lovastatin in children with neurofibromatosis type 1

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