Study Summary
This trial will assess the safety and clinical benefit of N-acetylcysteine (NAC) as a treatment for children with neurofibromatosis type 1 (NF1).
Eligible Conditions
- Neurofibromatosis Type 1
Treatment Effectiveness
Effectiveness Progress
Study Objectives
1 Primary · 3 Secondary · Reporting Duration: through 12 weeks (at weeks 0, 8, and 12)
Week 12
Change from Baseline in ADHD Symptoms as Reported via Parent/Teacher Surveys
Change from Baseline in Microstructural Properties of Brain Tissue Visualized by Magnetic Resonance Imaging (MRI)
Change from Baseline in Motor Function Measured by Physical and Neurological Examination for Subtle Signs (PANESS)
Change from Baseline in Motor Function and Physiology Measured by Transcranial Magnetic Stimulation (TMS)
Trial Safety
Safety Progress
This is further along than 68% of similar trials
Trial Design
2 Treatment Groups
N-Acetylcysteine (NAC)
1 of 2
Placebo
1 of 2
Experimental Treatment
Non-Treatment Group
58 Total Participants · 2 Treatment Groups
Primary Treatment: N-Acetyl cysteine · Has Placebo Group · Phase 2
N-Acetylcysteine (NAC)
Drug
Experimental Group · 1 Intervention: N-Acetyl cysteine · Intervention Types: DrugPlacebo
Other
PlaceboComparator Group · 1 Intervention: Placebo · Intervention Types: OtherTreatment
First Studied
Drug Approval Stage
How many patients have taken this drug
Montelukast
FDA approved
Trial Logistics
Trial Timeline
Screening: ~3 weeks
Treatment: Varies
Reporting: through 12 weeks (at weeks 0, 8, and 12)
Who is running the clinical trial?
Children's Hospital Medical Center, CincinnatiLead Sponsor
765 Previous Clinical Trials
5,422,902 Total Patients Enrolled
United States Department of DefenseFED
792 Previous Clinical Trials
213,235 Total Patients Enrolled
1 Trials studying Neurofibromatosis
19 Patients Enrolled for Neurofibromatosis
Carlos E Prada, MDPrincipal InvestigatorChildren's Hospital Medical Center, Cincinnati
2 Previous Clinical Trials
91 Total Patients Enrolled
Donald Gilbert, MD MSPrincipal InvestigatorChildren's Hospital Medical Center, Cincinnati
Eligibility Criteria
Age 8 - 16 · All Participants · 5 Total Inclusion Criteria
Mark “Yes” if the following statements are true for you:References
- Mayes, Debra A., Tilat A. Rizvi, Haley Titus-Mitchell, Rachel Oberst, Georgianne M. Ciraolo, Charles V. Vorhees, Andrew P. Robinson, et al.. 2013. “Nf1 Loss and Ras Hyperactivation in Oligodendrocytes Induce Nos-driven Defects in Myelin and Vasculature”. Cell Reports. Elsevier BV. doi:10.1016/j.celrep.2013.08.011.
- Fernandes, Brisa S., Olivia M. Dean, Seetal Dodd, Gin S. Malhi, and Michael Berk. 2016. “n-acetylcysteine in Depressive Symptoms and Functionality”. The Journal of Clinical Psychiatry. Physicians Postgraduate Press, Inc. doi:10.4088/jcp.15r09984.
- Information/NLM/NIH, NCBI. 2017. “Gprobe”. GitHub repository. https://github.com/ncbi/gprobe.
- Wassermann, Eric M. 1998. “Risk and Safety of Repetitive Transcranial Magnetic Stimulation: Report and Suggested Guidelines from the International Workshop on the Safety of Repetitive Transcranial Magnetic Stimulation, June 5–7, 1996”. Electroencephalography and Clinical Neurophysiology/evoked Potentials Section. Elsevier BV. doi:10.1016/s0168-5597(97)00096-8.
- Acosta, Maria T., Carrie E. Bearden, Xavier F. Castellanos, Laurie Cutting, Ype Elgersma, Gerard Gioia, David H. Gutmann, et al.. 2012. “The Learning Disabilities Network (leadnet): Using Neurofibromatosis Type 1 (NF1) as a Paradigm for Translational Research”. American Journal of Medical Genetics Part A. Wiley. doi:10.1002/ajmg.a.35535.
- Gilbert, D. L., K. M. Isaacs, M. Augusta, L. K. MacNeil, and S. H. Mostofsky. 2011. “Motor Cortex Inhibition: A Marker of ADHD Behavior and Motor Development in Children”. Neurology. Ovid Technologies (Wolters Kluwer Health). doi:10.1212/wnl.0b013e31820c2ebd.
- Axelrod, Bradley N.. 2002. “Validity of the Wechsler Abbreviated Scale of Intelligence and Other Very Short Forms of Estimating Intellectual Functioning”. Assessment. SAGE Publications. doi:10.1177/1073191102009001003.
- Etherton, Joseph L., Kevin J. Bianchini, Megan A. Ciota, Matthew T. Heinly, and Kevin W. Greve. 2006. “Pain, Malingering and the WAIS-III Working Memory Index”. The Spine Journal. Elsevier BV. doi:10.1016/j.spinee.2005.05.382.
- Casnar, Christy L., Kelly M. Janke, Faye van der Fluit, Natalie G. Brei, and Bonita P. Klein-Tasman. 2014. “Relations Between Fine Motor Skill and Parental Report of Attention in Young Children with Neurofibromatosis Type 1”. Journal of Clinical and Experimental Neuropsychology. Informa UK Limited. doi:10.1080/13803395.2014.957166.
- Walsh, Karin S., Jennifer Janusz, Pamela L. Wolters, Staci Martin, Bonita P. Klein-Tasman, Mary Anne Toledo-Tamula, Heather L. Thompson, et al.. 2016. “Neurocognitive Outcomes in Neurofibromatosis Clinical Trials”. Neurology. Ovid Technologies (Wolters Kluwer Health). doi:10.1212/wnl.0000000000002928.
- Chen, Yu-Wen, Hui-Ching Lin, Ming-Chong Ng, Ya-Hsin Hsiao, Chao-Chuan Wang, Po-Wu Gean, and Po See Chen. 2014. “Activation of Mglur2/3 Underlies the Effects of N-acetylcystein on Amygdala-associated Autism-like Phenotypes in a Valproate-induced Rat Model of Autism”. Frontiers in Behavioral Neuroscience. Frontiers Media SA. doi:10.3389/fnbeh.2014.00219.
- Berk, Michael, Olivia Dean, Sue M. Cotton, Clarissa S. Gama, Flavio Kapczinski, Brisa S. Fernandes, Kristy Kohlmann, et al.. 2011. “The Efficacy of N-acetylcysteine as an Adjunctive Treatment in Bipolar Depression: An Open Label Trial”. Journal of Affective Disorders. Elsevier BV. doi:10.1016/j.jad.2011.06.005.
- Walkup, John T., Michael J. Labellarte, Mark A. Riddle, Daniel S. Pine, Laurence Greenhill, Rachel Klein, Mark Davies, et al.. 2001. “Fluvoxamine for the Treatment of Anxiety Disorders in Children and Adolescents”. New England Journal of Medicine. Massachusetts Medical Society. doi:10.1056/nejm200104263441703.
- Information/NLM/NIH, NCBI. 2017. “Gprobe”. GitHub repository. https://github.com/ncbi/gprobe.
- Acosta, Maria T., Gerard A. Gioia, and Alcino J. Silva. 2006. “Neurofibromatosis Type 1: New Insights into Neurocognitive Issues”. Current Neurology and Neuroscience Reports. Springer Science and Business Media LLC. doi:10.1007/s11910-996-0036-5.
- Ballester, Roymarie, Douglas Marchuk, Mark Boguski, Ann Saulino, Roxanne Letcher, Michael Wigler, and Francis Collins. 1990. “The NF1 Locus Encodes a Protein Functionally Related to Mammalian GAP and Yeast IRA Proteins”. Cell. Elsevier BV. doi:10.1016/0092-8674(90)90151-4.
- Tokumura, Akira, Eiji Majima, Yuko Kariya, Kyoko Tominaga, Kentaro Kogure, Katsuhiko Yasuda, and Kenji Fukuzawa. 2002. “Identification of Human Plasma Lysophospholipase D, a Lysophosphatidic Acid-producing Enzyme, as Autotaxin, a Multifunctional Phosphodiesterase”. Journal of Biological Chemistry. Elsevier BV. doi:10.1074/jbc.m205623200.
- Hardan, Antonio Y., Lawrence K. Fung, Robin A. Libove, Tetyana V. Obukhanych, Surekha Nair, Leonore A. Herzenberg, Thomas W. Frazier, and Rabindra Tirouvanziam. 2012. “A Randomized Controlled Pilot Trial of Oral N-acetylcysteine in Children with Autism”. Biological Psychiatry. Elsevier BV. doi:10.1016/j.biopsych.2012.01.014.
- Pride, Natalie, Jonathan M. Payne, Richard Webster, E. Arthur Shores, Caroline Rae, and Kathryn N. North. 2010. “Corpus Callosum Morphology and Its Relationship to Cognitive Function in Neurofibromatosis Type 1”. Journal of Child Neurology. SAGE Publications. doi:10.1177/0883073809350723.
- Dennis, Jameel, Michael A. White, Audrey D. Forrest, Larra M. Yuelling, Luciana Nogaroli, Fatemah S. Afshari, Michael A. Fox, and Babette Fuss. 2008. “Phosphodiesterase-iα/autotaxin's MORFO Domain Regulates Oligodendroglial Process Network Formation and Focal Adhesion Organization”. Molecular and Cellular Neuroscience. Elsevier BV. doi:10.1016/j.mcn.2007.10.018.
- Rosser, Tena L., and Roger J. Packer. 2003. “Neurocognitive Dysfunction in Children with Neurofibromatosis Type 1”. Current Neurology and Neuroscience Reports. Springer Science and Business Media LLC. doi:10.1007/s11910-003-0064-3.
- Wang, Yuan, Edward Kim, Xiaojing Wang, Bennett G. Novitch, Kazuaki Yoshikawa, Long-Sheng Chang, and Yuan Zhu. 2012. “ERK Inhibition Rescues Defects in Fate Specification of Nf1-deficient Neural Progenitors and Brain Abnormalities”. Cell. Elsevier BV. doi:10.1016/j.cell.2012.06.034.
- Garcia, Ricardo J., Lisa Francis, Maha Dawood, Zhi-Wei Lai, Stephen V. Faraone, and Andras Perl. 2013. “Brief Report: Attention Deficit and Hyperactivity Disorder Scores Are Elevated and Respond Ton-acetylcysteine Treatment in Patients with Systemic Lupus Erythematosus”. Arthritis & Rheumatism. Wiley. doi:10.1002/art.37893.
- Karlsgodt, Katherine H., Tena Rosser, Evan S. Lutkenhoff, Tyrone D. Cannon, Alcino Silva, and Carrie E. Bearden. 2012. “Alterations in White Matter Microstructure in Neurofibromatosis-1”. Edited by Emanuele Buratti. Plos ONE. Public Library of Science (PLoS). doi:10.1371/journal.pone.0047854.
- Chen, Tina H, Steve W Wu, Jeffrey A Welge, Stephan G Dixon, Nasrin Shahana, David A Huddleston, Adam R Sarvis, Floyd R Sallee, and Donald L Gilbert. 2014. “Reduced Short Interval Cortical Inhibition Correlates with Atomoxetine Response in Children with Attention-deficit Hyperactivity Disorder (ADHD)”. Journal of Child Neurology. SAGE Publications. doi:10.1177/0883073813513333.
- Fox, Michael A., Raymond J. Colello, Wendy B. Macklin, and Babette Fuss. 2003. “Phosphodiesterase-iα/autotaxin: A Counteradhesive Protein Expressed by Oligodendrocytes During Onset of Myelination”. Molecular and Cellular Neuroscience. Elsevier BV. doi:10.1016/s1044-7431(03)00073-3.
- Erkan, Elif, Xueheng Zhao, Kenneth Setchell, and Prasad Devarajan. 2015. “Distinct Urinary Lipid Profile in Children with Focal Segmental Glomerulosclerosis”. Pediatric Nephrology. Springer Science and Business Media LLC. doi:10.1007/s00467-015-3239-7.
- Fox MA, Colello RJ, Macklin WB, Fuss B. Phosphodiesterase-Ialpha/autotaxin: a counteradhesive protein expressed by oligodendrocytes during onset of myelination. Mol Cell Neurosci. 2003 Jul;23(3):507-19. doi: 10.1016/s1044-7431(03)00073-3.
- Ballester R, Marchuk D, Boguski M, Saulino A, Letcher R, Wigler M, Collins F. The NF1 locus encodes a protein functionally related to mammalian GAP and yeast IRA proteins. Cell. 1990 Nov 16;63(4):851-9. doi: 10.1016/0092-8674(90)90151-4.
- Rosser TL, Packer RJ. Neurocognitive dysfunction in children with neurofibromatosis type 1. Curr Neurol Neurosci Rep. 2003 Mar;3(2):129-36. doi: 10.1007/s11910-003-0064-3.
- Fluvoxamine for the treatment of anxiety disorders in children and adolescents. The Research Unit on Pediatric Psychopharmacology Anxiety Study Group. N Engl J Med. 2001 Apr 26;344(17):1279-85. doi: 10.1056/NEJM200104263441703.
- Axelrod BN. Validity of the Wechsler abbreviated scale of intelligence and other very short forms of estimating intellectual functioning. Assessment. 2002 Mar;9(1):17-23. doi: 10.1177/1073191102009001003.
- Wassermann EM. Risk and safety of repetitive transcranial magnetic stimulation: report and suggested guidelines from the International Workshop on the Safety of Repetitive Transcranial Magnetic Stimulation, June 5-7, 1996. Electroencephalogr Clin Neurophysiol. 1998 Jan;108(1):1-16. doi: 10.1016/s0168-5597(97)00096-8.
- Mills KR, Nithi KA. Corticomotor threshold to magnetic stimulation: normal values and repeatability. Muscle Nerve. 1997 May;20(5):570-6. doi: 10.1002/(sici)1097-4598(199705)20:53.0.co;2-6.
- Tokumura A, Majima E, Kariya Y, Tominaga K, Kogure K, Yasuda K, Fukuzawa K. Identification of human plasma lysophospholipase D, a lysophosphatidic acid-producing enzyme, as autotaxin, a multifunctional phosphodiesterase. J Biol Chem. 2002 Oct 18;277(42):39436-42. doi: 10.1074/jbc.M205623200. Epub 2002 Aug 9.
- Acosta MT, Gioia GA, Silva AJ. Neurofibromatosis type 1: new insights into neurocognitive issues. Curr Neurol Neurosci Rep. 2006 Mar;6(2):136-43. doi: 10.1007/s11910-996-0036-5.
- Fernandes BS, Dean OM, Dodd S, Malhi GS, Berk M. N-Acetylcysteine in depressive symptoms and functionality: a systematic review and meta-analysis. J Clin Psychiatry. 2016 Apr;77(4):e457-66. doi: 10.4088/JCP.15r09984.
- Ziemann U. Intracortical inhibition and facilitation in the conventional paired TMS paradigm. Electroencephalogr Clin Neurophysiol Suppl. 1999;51:127-36. No abstract available.
- Acosta MT, Bearden CE, Castellanos FX, Cutting L, Elgersma Y, Gioia G, Gutmann DH, Lee YS, Legius E, Muenke M, North K, Parada LF, Ratner N, Hunter-Schaedle K, Silva AJ. The Learning Disabilities Network (LeaDNet): using neurofibromatosis type 1 (NF1) as a paradigm for translational research. Am J Med Genet A. 2012 Sep;158A(9):2225-32. doi: 10.1002/ajmg.a.35535. Epub 2012 Jul 20. Erratum In: Am J Med Genet A. 2013 Jan;161A(1):236. Castellanos, Xavier F [corrected to Castellanos, F Xavier].
- 2020. "Antioxidant Therapy With N-acetylcysteine for Children With Neurofibromatosis Type 1". ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT04481048.
Frequently Asked Questions
Are there any available vacancies for this treatment program?
"This clinical trial is actively searching for participants. The trial was first posted on December 15th 2020 and was last updated on February 24th 2022." - Anonymous Online Contributor
Unverified Answer
What other research studies have there been on N-Acetyl cysteine?
"As of right now, 83 different clinical trials are studying the effects of N-Acetyl cysteine. Out of those 83 live studies, 19 are in Phase 3 testing. The majority of these studies are based out Lopburi and Songkhla in Thailand; however, there are 316 total locations running similar tests." - Anonymous Online Contributor
Unverified Answer
Are the patients in this clinical trial restricted to those over 20 years old?
"In order to participate in this particular clinical trial, children aged 8 to 16 years old are eligible. Out of the total 150 trials, 60 are for patients below 18 years of age and 90 are for those over 65." - Anonymous Online Contributor
Unverified Answer
What medical conditions is N-Acetyl cysteine used to treat?
"The common cold, acetaminophen, and other conditions can often be treated effectively with N-Acetyl cysteine. This medication is most well-known, however, for its asthma relief properties." - Anonymous Online Contributor
Unverified Answer
For which patient population is this research project intended?
"This trial is aiming to enroll 58 individuals that have watson syndrome. These participants will be between 8 and 16 years old. To meet the qualifications for this study, applicants must also satisfy the following conditions: Be male or female, no more than 16 years and 6 months old, have an IQ of 70 or above (this must be from a neurocognitive test administered in last 3 years or during enrollment), meet NIH criteria for NF1 diagnosis, abnormal PANESS score (this must be at or above mean based on age and sex), currently taking stimulant medication or any other psychotropic drug but with a stable 30-day dose before" - Anonymous Online Contributor
Unverified Answer
Has N-Acetyl cysteine received authorization from the FDA?
"N-Acetyl cysteine has not been proven effective yet, however, it did receive a score of 2 due to data collected that supports its safety profile." - Anonymous Online Contributor
Unverified Answer