MRS to Determine Neuroinflammation and Oxidative Stress in MPS I

NCT03576729 | Completed DMC

• 2 other identifiers: STUDY00003680U54NS065768
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Neuroinflammation and oxidative stress have been shown to be present in persons with mucopolysaccharidosis type I (MPS I), but their effect on disease severity and disease progression is unknown. The investigator intends to employ brain magnetic resonance spectroscopy (MRS), a non-invasive technique, along with analysis of neuroinflammation and oxidative stress biomarkers in the blood, to measure and determine the level of oxidative stress and neuroinflammation, and their impact on clinical variability in MPS I patients.

Conditions

Mucopolysaccharidosis Type I

Keywords

Mucopolysaccharidosis type I; MPS I; MPS IH; MPS IHS; MPS IS; Mucopolysaccharidosis I

Outcome Measures

Primary Outcomes (1)

• Brain Magnetic Resonance Imaging/Magnetic Resonance Spectroscopy (MRI/MRS)

  In a single session, each participant will undergo unsedated brain magnetic resonance imaging/magnetic resonance spectroscopy (MRI/MRS) to determine the presence and extent of any brain neuroinflammation. These data will be acquired on the 7-Tesla Siemens Prisma scanner at the Center for Magnetic Resonance Research (CMRR) at the University of Minnesota in Minneapolis.

  1 day -Single encounter during an appointment which is set at time of study enrollment.

Secondary Outcomes (14)

• Presence and Level of Neuroinflammatory Biomarker MIP-1alpha

  1 day -Single blood draw performed at the same time as the single neuroimaging encounter.

• Presence and Level of Regulated and Normal T cell Expressed and Secreted (RANTES)

  1 day -Single blood draw performed at the same time as the single neuroimaging encounter.

• Presence and Level of Tumor Necrosis Factor Alpha (TNF-α)

  1 day -Single blood draw performed at the same time as the single neuroimaging encounter.

• Presence and Level of Interferon-gamma (IFN-γ)

  1 day -Single blood draw performed at the same time as the single neuroimaging encounter.

• Presence and Level of Interleukin 1 beta (IL1β)

  1 day -Single blood draw performed at the same time as the single neuroimaging encounter.

Study Arms (3)

Hurler syndrome participants

Participants who have MPS IH, also called Hurler syndrome

Hurler-Scheie/Scheie participants

Participants who have either MPS IHS or MPS IS. MPS IHS is also called Hurler-Scheie syndrome. MPS IS is also called Scheie syndrome.

Healthy Controls

Age-matched healthy controls

Eligibility Criteria

• Age: 6 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

20 subjects who have MPS I and are 6 years of age or older will be recruited for this study: 10 with severe MPS I (post-HCT Hurler syndrome); and 10 with attenuated MPS I (Hurler Scheie or Scheie syndrome, and receiving ERT). In addition, 10 normal healthy controls, 6 years of age or older, will be recruited for this study.

You may qualify if:

• MPS I participants must meet the following:
• Diagnosis of Hurler syndrome, OR Hurler-Scheie syndrome, OR Scheie syndrome
• years of age or older at time of screening
• Healthy control participants must meet all of the following:
• Absence of neurological disorder
• years of age or older at time of screening

You may not qualify if:

• Persons who have any of the following will not be enrolled in this study:
• Any surgically implanted pacemaker
• Any indwelling electronic device, including programmable shunts
• Orthodontic braces, unless non-metallic
• Other implanted metal in the body other than titanium
• An inability or unwillingness to complete an MRI/MRS because of low cognitive function or behavioral dysregulation
• Pregnancy

Sponsors & Collaborators

• University of Minnesota: lead
• Rare Diseases Clinical Research Network: collaborator
• National Center for Advancing Translational Sciences (NCATS): collaborator
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator
• Lysosomal Disease Network: collaborator

Study Sites (1)

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Related Publications (2)

• 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.

  PMID: 29111092 BACKGROUND

• 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 across the spectrum of mucopolysaccharidosis type I: Age, severity, and treatment. Mol Genet Metab. 2015 Sep-Oct;116(1-2):61-8. doi: 10.1016/j.ymgme.2015.06.002. Epub 2015 Jun 17.

  PMID: 26095521 BACKGROUND

Related Links

• Rare Diseases Clinical Research Network's web site

Biospecimen

Retention: SAMPLES WITHOUT DNA

blood sample

MeSH Terms

Conditions

Mucopolysaccharidosis I

Condition Hierarchy (Ancestors)

Mucopolysaccharidoses; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lysosomal Storage Diseases; Mucinoses; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Igor Nestrasil, PhD, MD

  University of Minnesota

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 22, 2018
• First Posted: July 3, 2018
• Study Start: November 1, 2018
• Primary Completion: August 31, 2019
• Study Completion: August 31, 2019
• Last Updated: November 1, 2019

Record last verified: 2019-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, CSR
• Time Frame: De-identified individual data are input to the NIH-funded Rare Diseases Clinical Research Network's Data Management \& Coordinating Center ("DMCC") as these data become available following participants' appointments. After the conclusion of this study and analysis of its data, these data will become part of the database of Genotypes and Phenotypes ("dbGaP"), which is part of the National Center for Biotechnology Information, U.S. National Library of Medicine. These data will remain available in this database indefinitely.
• Access Criteria: Access criteria are determined by the National Center for Biotechnology Information, U.S. National Library of Medicine.

Locations

US (1)