Mucopolysaccharidosis Type I Clinical Trial
Official title:
Longitudinal Studies of Brain Structure and Function in MPS Disorders
Verified date | September 2019 |
Source | University of Minnesota - Clinical and Translational Science Institute |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Observational |
Neurobehavioral function and quality of life are compromised in many patients with mucopolysaccharidosis (MPS) disorders. The long-term goals of this research are to: 1) more accurately inform patients/parents regarding potential neurobehavioral outcomes; 2) develop sensitive measures of disease progression and central nervous system (CNS) treatment outcome; and 3) help clinical researchers develop direct treatments for specific brain structures/functions. The investigators hypothesize that specific and localized neuroimaging and neuropsychological findings and their relationship will be distinct for each MPS disorder. It is further hypothesized that without treatment, functions will decline and structure will change over time in a predictable fashion, and will be related to locus of abnormality and stage of disease.
Status | Completed |
Enrollment | 100 |
Est. completion date | August 31, 2019 |
Est. primary completion date | August 31, 2019 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 6 Years and older |
Eligibility |
Inclusion Criteria: - Any MPS I, II, IV, VI or VII child or adult aged 6 years of age or older Exclusion Criteria: - Exclusion Criteria for Neuroimaging: - Participants with: - Pacemakers - Any indwelling electronic device including programmable shunts - Orthodontic braces unless they are not made of metal - Other implanted metal in the body other than titanium - Unable to stay still during MRI because of low cognitive function, behavioral dysregulation, or young age, if the patient is not a clinical patient having sedation/anesthesia - Pregnancy - Exclusion Criteria for Neuropsychological and Neurobehavioral Testing - Participants who: - Are too functionally impaired for testing |
Country | Name | City | State |
---|---|---|---|
Canada | Hospital for Sick Children | Toronto | Ontario |
United States | University of Minnesota | Minneapolis | Minnesota |
United States | New York University | New York | New York |
United States | Oakland Children's Hospital | Oakland | California |
Lead Sponsor | Collaborator |
---|---|
University of Minnesota - Clinical and Translational Science Institute | Lysosomal Disease Network, National Center for Advancing Translational Science (NCATS), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institute of Neurological Disorders and Stroke (NINDS), Rare Diseases Clinical Research Network |
United States, Canada,
Ahmed A, Rudser K, Kunin-Batson A, Delaney K, Whitley C, Shapiro E. Mucopolysaccharidosis (MPS) Physical Symptom Score: Development, Reliability, and Validity. JIMD Rep. 2016;26:61-8. doi: 10.1007/8904_2015_485. Epub 2015 Aug 25. — View Citation
Ahmed A, Shapiro E, Rudser K, Kunin-Batson A, King K, Whitley CB. Association of somatic burden of disease with age and neuropsychological measures in attenuated mucopolysaccharidosis types I, II and VI. Mol Genet Metab Rep. 2016 Apr 1;7:27-31. doi: 10.10 — View Citation
Ahmed A, Whitley CB, Cooksley R, Rudser K, Cagle S, Ali N, Delaney K, Yund B, Shapiro E. Neurocognitive and neuropsychiatric phenotypes associated with the mutation L238Q of the a-L-iduronidase gene in Hurler-Scheie syndrome. Mol Genet Metab. 2014 Feb;111 — View Citation
Aldenhoven M, Wynn RF, Orchard PJ, O'Meara A, Veys P, Fischer A, Valayannopoulos V, Neven B, Rovelli A, Prasad VK, Tolar J, Allewelt H, Jones SA, Parini R, Renard M, Bordon V, Wulffraat NM, de Koning TJ, Shapiro EG, Kurtzberg J, Boelens JJ. Long-term outcome of Hurler syndrome patients after hematopoietic cell transplantation: an international multicenter study. Blood. 2015 Mar 26;125(13):2164-72. doi: 10.1182/blood-2014-11-608075. Epub 2015 Jan 26. — View Citation
Braunlin E, Orchard PJ, Whitley CB, Schroeder L, Reed RC, Manivel JC. Unexpected coronary artery findings in mucopolysaccharidosis. Report of four cases and literature review. Cardiovasc Pathol. 2014 May-Jun;23(3):145-51. doi: 10.1016/j.carpath.2014.01.001. Epub 2014 Jan 10. Review. — View Citation
Eisengart JB, Jarnes J, Ahmed A, Nestrasil I, Ziegler R, Delaney K, Shapiro E, Whitley C. Long-term cognitive and somatic outcomes of enzyme replacement therapy in untransplanted Hurler syndrome. Mol Genet Metab Rep. 2017 Sep 27;13:64-68. doi: 10.1016/j.y — View Citation
Eisengart JB, Rudser KD, Tolar J, Orchard PJ, Kivisto T, Ziegler RS, Whitley CB, Shapiro EG. Enzyme replacement is associated with better cognitive outcomes after transplant in Hurler syndrome. J Pediatr. 2013 Feb;162(2):375-80.e1. doi: 10.1016/j.jpeds.20 — View Citation
Eisengart JB, Rudser KD, Xue Y, Orchard P, Miller W, Lund T, Van der Ploeg A, Mercer J, Jones S, Mengel KE, Gökce S, Guffon N, Giugliani R, de Souza CFM, Shapiro EG, Whitley CB. Long-term outcomes of systemic therapies for Hurler syndrome: an international multicenter comparison. Genet Med. 2018 Nov;20(11):1423-1429. doi: 10.1038/gim.2018.29. Epub 2018 Mar 8. — View Citation
Janzen D, Delaney KA, Shapiro EG. Cognitive and adaptive measurement endpoints for clinical trials in mucopolysaccharidoses types I, II, and III: A review of the literature. Mol Genet Metab. 2017 Jun;121(2):57-69. doi: 10.1016/j.ymgme.2017.05.005. Epub 2017 May 8. Review. — View Citation
Kunin-Batson AS, Shapiro EG, Rudser KD, Lavery CA, Bjoraker KJ, Jones SA, Wynn RF, Vellodi A, Tolar J, Orchard PJ, Wraith JE. Long-Term Cognitive and Functional Outcomes in Children with Mucopolysaccharidosis (MPS)-IH (Hurler Syndrome) Treated with Hematopoietic Cell Transplantation. JIMD Rep. 2016;29:95-102. Epub 2016 Jan 30. — View Citation
Nestrasil I, Vedolin L. Quantitative neuroimaging in mucopolysaccharidoses clinical trials. Mol Genet Metab. 2017 Dec;122S:17-24. doi: 10.1016/j.ymgme.2017.09.006. Epub 2017 Sep 15. Review. — View Citation
Ou L, Herzog TL, Wilmot CM, Whitley CB. Standardization of a-L-iduronidase enzyme assay with Michaelis-Menten kinetics. Mol Genet Metab. 2014 Feb;111(2):113-5. doi: 10.1016/j.ymgme.2013.11.009. Epub 2013 Nov 26. — View Citation
Polgreen LE, Kunin-Batson A, Rudser K, Vehe RK, Utz JJ, Whitley CB, Dickson P. Pilot study of the safety and effect of adalimumab on pain, physical function, and musculoskeletal disease in mucopolysaccharidosis types I and II. Mol Genet Metab Rep. 2017 Jan 15;10:75-80. doi: 10.1016/j.ymgmr.2017.01.002. eCollection 2017 Mar. — View Citation
Polgreen LE, Thomas W, Orchard PJ, Whitley CB, Miller BS. Effect of recombinant human growth hormone on changes in height, bone mineral density, and body composition over 1-2 years in children with Hurler or Hunter syndrome. Mol Genet Metab. 2014 Feb;111(2):101-6. doi: 10.1016/j.ymgme.2013.11.013. Epub 2013 Dec 11. — View Citation
Polgreen LE, Vehe RK, Rudser K, Kunin-Batson A, Utz JJ, Dickson P, Shapiro E, Whitley CB. Elevated TNF-a is associated with pain and physical disability in mucopolysaccharidosis types I, II, and VI. Mol Genet Metab. 2016 Apr;117(4):427-30. doi: 10.1016/j. — View Citation
Shapiro E, Guler OE, Rudser K, Delaney K, Bjoraker K, Whitley C, Tolar J, Orchard P, Provenzale J, Thomas KM. An exploratory study of brain function and structure in mucopolysaccharidosis type I: long term observations following hematopoietic cell transpl — View Citation
Shapiro EG, Nestrasil I, Rudser K, Delaney K, Kovac V, Ahmed A, Yund B, Orchard PJ, Eisengart J, Niklason GR, Raiman J, Mamak E, Cowan MJ, Bailey-Olson M, Harmatz P, Shankar SP, Cagle S, Ali N, Steiner RD, Wozniak J, Lim KO, Whitley CB. Neurocognition acr — View Citation
Shapiro EG, Rudser K, Ahmed A, Steiner RD, Delaney KA, Yund B, King K, Kunin-Batson A, Eisengart J, Whitley CB. A longitudinal study of emotional adjustment, quality of life and adaptive function in attenuated MPS II. Mol Genet Metab Rep. 2016 Apr 1;7:32- — View Citation
Shapiro EG, Whitley CB, Eisengart JB. Beneath the floor: re-analysis of neurodevelopmental outcomes in untreated Hurler syndrome. Orphanet J Rare Dis. 2018 May 11;13(1):76. doi: 10.1186/s13023-018-0817-3. — View Citation
Stevenson DA, Rudser K, Kunin-Batson A, Fung EB, Viskochil D, Shapiro E, Orchard PJ, Whitley CB, Polgreen LE. Biomarkers of bone remodeling in children with mucopolysaccharidosis types I, II, and VI. J Pediatr Rehabil Med. 2014;7(2):159-65. doi: 10.3233/PRM-140285. — View Citation
Taylor NE, Dengel DR, Lund TC, Rudser KD, Orchard PJ, Steinberger J, Whitley CB, Polgreen LE. Isokinetic muscle strength differences in patients with mucopolysaccharidosis I, II, and VI. J Pediatr Rehabil Med. 2014;7(4):353-60. doi: 10.3233/PRM-140305. — View Citation
van der Lee JH, Morton J, Adams HR, Clarke L, Ebbink BJ, Escolar ML, Giugliani R, Harmatz P, Hogan M, Jones S, Kearney S, Muenzer J, Rust S, Semrud-Clikeman M, Wijburg FA, Yu ZF, Janzen D, Shapiro E. Cognitive endpoints for therapy development for neuronopathic mucopolysaccharidoses: Results of a consensus procedure. Mol Genet Metab. 2017 Jun;121(2):70-79. doi: 10.1016/j.ymgme.2017.05.004. Epub 2017 May 6. — View Citation
Whitley CB, Cleary M, Eugen Mengel K, Harmatz P, Shapiro E, Nestrasil I, Haslett P, Whiteman D, Alexanderian D. Observational Prospective Natural History of Patients with Sanfilippo Syndrome Type B. J Pediatr. 2018 Jun;197:198-206.e2. doi: 10.1016/j.jpeds.2018.01.044. Epub 2018 Apr 13. — View Citation
Wolf DA, Banerjee S, Hackett PB, Whitley CB, McIvor RS, Low WC. Gene therapy for neurologic manifestations of mucopolysaccharidoses. Expert Opin Drug Deliv. 2015 Feb;12(2):283-96. doi: 10.1517/17425247.2015.966682. Epub 2014 Dec 16. Review. — View Citation
Yund B, Rudser K, Ahmed A, Kovac V, Nestrasil I, Raiman J, Mamak E, Harmatz P, Steiner R, Lau H, Vekaria P, Wozniak JR, Lim KO, Delaney K, Whitley C, Shapiro EG. Cognitive, medical, and neuroimaging characteristics of attenuated mucopolysaccharidosis type — View Citation
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Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Change in Cognitive Ability (IQ) | Age-appropriate IQ tests will be administered at baseline and during subject's annual visit. | Baseline, Year 1, Year 2, Year 3 | |
Secondary | Change in Quality of Life | Age-appropriate Quality of Life measures will be administered at baseline and during subject's annual visit. | Baseline, Year 1, Year 2, Year 3 | |
Secondary | Change in Neuropsychological Status | Memory, Attention, Visual Spatial, and Visual Motor functions will be assessed with age-appropriate measures administered at baseline and during subject's annual visit. | Baseline, Year 1, Year 2, Year 3 | |
Secondary | Change in Emotional and Behavioral Health | Age-appropriate measures of emotional and behavioral health will be administered at baseline and during subject's annual visit. | Baseline, Year 1, Year 2, Year 3 | |
Secondary | Change Shown in Magnetic Resonance Imaging of the Brain | Magnetic resonance imaging of each subject's brain will be performed at baseline and during subject's annual visit to acquire volumetric, diffusion tensor imaging (DTI), and resting state data. These data will be analyzed to identify any changes occurring over time. | Baseline, Year 1, Year 2, Year 3 | |
Secondary | Change in Adaptive Functions | Vineland Adaptive Behavior Scales, a measure of communication, daily living skills, socialization and motor function, will be administered at baseline and during subject's annual visit. | Baseline, Year 1, Year 2, Year 3 |
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