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Completed

NCT Number: NCT03576729

MRS to Determine Neuroinflammation and Oxidative Stress in MPS I

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.

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Key information

Conditions

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

Age range

6 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

About this study

Persons with MPS I have a wide range of clinical manifestations including central nervous system (CNS) impairment. The role of neuroinflammation and oxidative stress is one avenue of investigation which may clarify the broad neurological impairment in MPS I. Finding biomarkers that accurately describe the underlying and ongoing brain pathology is a key not only to understanding the disease, but also to understanding the possibility of new therapeutic approaches for MPS I patients.

The investigator will compare patients with Hurler syndrome, and Hurler-Scheie or Scheie syndrome, with healthy controls. There will be 10 participants in each group, resulting in a total of 30 participants. Within the Hurler-Scheie or Scheie syndrome group, the investigator will examine the association of clinical severity with the proposed measures. These findings might help determine whether hematopoietic cell transplantation (HCT), which is the treatment for Hurler syndrome patients, results in decreased oxidative stress and neuroinflammation as compared to Hurler-Scheie or Scheie syndrome patients, who are treated by enzyme replacement therapy (ERT). Additionally, these findings might help determine whether therapies directed at reducing neuroinflammation and oxidative stress in MPS I could enhance neurological outcomes.

Study hypothesis: neuroinflammation and oxidative stress are present in MPS I subjects and are reflective of disease severity.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

MPS I participants must meet the following:

  • Diagnosis of Hurler syndrome, OR Hurler-Scheie syndrome, OR Scheie syndrome
  • 6 years of age or older at time of screening

Healthy control participants must meet all of the following:

  • Absence of neurological disorder
  • 6 years of age or older at time of screening

Exclusion criteria

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

Treatment and study plan

Primary outcomes

  1. Brain Magnetic Resonance Imaging/Magnetic Resonance Spectroscopy (MRI/MRS)

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

    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.

Secondary outcomes

  1. Presence and Level of Neuroinflammatory Biomarker MIP-1alpha

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

    The presence of macrophage inflammatory protein (MIP)-1α (MIP-1alpha) will be determined; and if present, the level of this inflammatory biomarker will be determined.

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

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

    The presence of 'regulated and normal T cell expressed and secreted' (referred to as RANTES), alternatively also known as chemokine (C-C motif) ligand 5, or CCL5, will be determined. If present, the level of this inflammatory biomarker will be determined.

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

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

    The presence of tumor necrosis factor alpha (TNF-α) will be determined. If present, the level of this inflammatory biomarker will be determined.

  4. Presence and Level of Interferon-gamma (IFN-γ)

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

    The presence of interferon-gamma (IFN-γ) will be determined. If present, the level of this autoinflammatory biomarker will be determined.

  5. Presence and Level of Interleukin 1 beta (IL1β)

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

    The presence of interleukin 1 beta (IL1β) will be determined. If present, the level of this inflammatory biomarker will be determined.

  6. Presence and Level of Interleukin 2 (IL2)

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

    The presence of interleukin 2 (IL2) will be determined. If present, the level of this inflammatory biomarker will be determined.

  7. Presence and Level of Interleukin 8 (IL8)

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

    The presence of interleukin 8 (IL8), alternatively referred to as chemokine (C-X-C motif) ligand 8, or CXCL8, will be determined. If present, the level of this inflammatory biomarker will be determined.

  8. Presence and Level of Total Glutathione

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

    The presence of total glutathione will be determined. If present, the level of this antioxidant will be determined.

  9. Determination of Blood Glutathione Redox Ratio

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

    The blood glutathione redox ratio will be determined.

  10. Presence and Level of Superoxide Dismutase (SOD)

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

    The presence of superoxide dismutase (SOD) will be determined. If present, the level of this antioxidant will be determined.

  11. Presence and Level of 8-isoprostane

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

    The presence of 8-isoprostane will be determined. If present, the level of this inflammatory biomarker will be determined.

  12. Presence and Levels of Thiobarbituric Acid Reactive Substances (TBARS)

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

    The presence of thiobarbituric acid reactive substances (TBARS), which are biomarkers of the damage produced by oxidative stress, will be determined. If present, the levels of these biomarkers will be determined.

  13. Presence and Level of 4-hydroxynonenal (4-HNE)

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

    The presence of 4-hydroxynonenal (4-HNE) will be determined. If present, the level of this oxidative stress biomarker will be determined.

  14. Presence and Level of Catalase

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

    The presence of catalase will be determined. If present, the level of this oxidative stress biomarker will be determined.

Sponsors and collaborators

Lead sponsor

University of Minnesota

Other

Collaborators

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

Registry information

Official study title

Magnetic Resonance Spectroscopy (MRS) to Determine Neuroinflammation and Oxidative Stress in MPS I

Important dates

Study start
2018
Primary completion
2019
Study completion
2019
First posted
Jul 3, 2018
Registry last updated
Nov 1, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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