Mucopolysaccharidosis Type INCT03576729
MRS to Determine Neuroinflammation and Oxidative Stress in MPS I
An observational study of Mucopolysaccharidosis Type I, run by University of Minnesota at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 6 years and olderHealthy volunteers can take part
- Conditions the study is for
- Mucopolysaccharidosis Type I
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Nov 2018to 31 Aug 2019
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 years and older
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
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.
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Minnesota
Minneapolis, Minnesota, 55455
About this study
Official title: Magnetic Resonance Spectroscopy (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.
Read the detailed description
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.
- Conditions
- Mucopolysaccharidosis Type I
- Keywords
- Mucopolysaccharidosis type I, MPS I, MPS IH, MPS IHS, MPS IS, Mucopolysaccharidosis I
- Medical subject headings
- Mucopolysaccharidosis I
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
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.
Measured: 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)
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.
Measured: 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)
The presence of tumor necrosis factor alpha (TNF-α) will be determined. If present, the level of this inflammatory biomarker will be determined.
Measured: 1 day -Single blood draw performed at the same time as the single neuroimaging encounter.
Presence and Level of Interferon-gamma (IFN-γ)
The presence of interferon-gamma (IFN-γ) will be determined. If present, the level of this autoinflammatory biomarker will be determined.
Measured: 1 day -Single blood draw performed at the same time as the single neuroimaging encounter.
Presence and Level of Interleukin 1 beta (IL1β)
The presence of interleukin 1 beta (IL1β) will be determined. If present, the level of this inflammatory biomarker will be determined.
Measured: 1 day -Single blood draw performed at the same time as the single neuroimaging encounter.
Presence and Level of Interleukin 2 (IL2)
The presence of interleukin 2 (IL2) will be determined. If present, the level of this inflammatory biomarker will be determined.
Measured: 1 day -Single blood draw performed at the same time as the single neuroimaging encounter.
Presence and Level of Interleukin 8 (IL8)
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.
Measured: 1 day -Single blood draw performed at the same time as the single neuroimaging encounter.
Presence and Level of Total Glutathione
The presence of total glutathione will be determined. If present, the level of this antioxidant will be determined.
Measured: 1 day -Single blood draw performed at the same time as the single neuroimaging encounter.
Determination of Blood Glutathione Redox Ratio
The blood glutathione redox ratio will be determined.
Measured: 1 day -Single blood draw performed at the same time as the single neuroimaging encounter.
Presence and Level of Superoxide Dismutase (SOD)
The presence of superoxide dismutase (SOD) will be determined. If present, the level of this antioxidant will be determined.
Measured: 1 day -Single blood draw performed at the same time as the single neuroimaging encounter.
Presence and Level of 8-isoprostane
The presence of 8-isoprostane will be determined. If present, the level of this inflammatory biomarker will be determined.
Measured: 1 day -Single blood draw performed at the same time as the single neuroimaging encounter.
Presence and Levels of Thiobarbituric Acid Reactive Substances (TBARS)
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.
Measured: 1 day -Single blood draw performed at the same time as the single neuroimaging encounter.
Presence and Level of 4-hydroxynonenal (4-HNE)
The presence of 4-hydroxynonenal (4-HNE) will be determined. If present, the level of this oxidative stress biomarker will be determined.
Measured: 1 day -Single blood draw performed at the same time as the single neuroimaging encounter.
Presence and Level of Catalase
The presence of catalase will be determined. If present, the level of this oxidative stress biomarker will be determined.
Measured: 1 day -Single blood draw performed at the same time as the single neuroimaging encounter.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jul 2018
- Study start1 Nov 2018
- Primary completion31 Aug 2019
- Study completion31 Aug 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Mucopolysaccharidosis Type IStudies of the same condition, open and under way.
- More trials run by University of MinnesotaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Other
- Time perspective
- Prospective
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Minnesota
- Sponsor type
- University, hospital or other
- Collaborators
- Rare Diseases Clinical Research Network, National Center for Advancing Translational Sciences (NCATS), National Institute of Neurological Disorders and Stroke (NINDS), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Lysosomal Disease Network
- Responsible party
- Sponsor
- Investigators
- Igor Nestrasil, PhD, MD, Principal investigator, University of Minnesota
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03576729
- Sponsor's protocol ID
- STUDY00003680
- Other IDs
- U54NS065768
- Status last verified
- Oct 2019
- First submitted
- 22 Jun 2018
- Last updated
- 1 Nov 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified individual data is input to the NIH-funded Rare Diseases Clinical Research Network's Data Management \& Coordinating Center ("DMCC"). Eventually this 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.
Publications
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.
PubMed 29111092Shapiro 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.
PubMed 26095521
Study at a glance
From the registry record, last updated by the sponsor on 1 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Magnetic Resonance Spectroscopy (MRS) to Determine Neuroinflammation and Oxidative Stress in MPS I
- ClinicalTrials.gov ID
- NCT03576729
- Acronym / sponsor ID
- STUDY00003680
- Conditions
- Mucopolysaccharidosis Type I
- Keywords
- Mucopolysaccharidosis type I, MPS I, MPS IH, MPS IHS, MPS IS, Mucopolysaccharidosis I
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- University of MinnesotaUniversity, hospital or other
- Collaborators
- Rare Diseases Clinical Research Network, National Center for Advancing Translational Sciences (NCATS), National Institute of Neurological Disorders and Stroke (NINDS), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Lysosomal Disease Network
- Study start
- 1 Nov 2018 (actual)
- Primary completion
- 31 Aug 2019 (actual)
- Study completion
- 31 Aug 2019 (actual)
- First posted
- 3 Jul 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Observational model
- Other
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 6 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- 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.
Key inclusion criteria (6 listed)
- Diagnosis of Hurler syndrome, OR Hurler-Scheie syndrome, OR Scheie syndrome
- 6 years of age or older at time of screening
- Absence of neurological disorder
- 6 years of age or older at time of screening
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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.
14 secondary outcomes
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.
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.
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.
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.
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.
Presence and Level of Interleukin 2 (IL2)
Time frame: 1 day -Single blood draw performed at the same time as the single neuroimaging encounter.
Presence and Level of Interleukin 8 (IL8)
Time frame: 1 day -Single blood draw performed at the same time as the single neuroimaging encounter.
Presence and Level of Total Glutathione
Time frame: 1 day -Single blood draw performed at the same time as the single neuroimaging encounter.
Determination of Blood Glutathione Redox Ratio
Time frame: 1 day -Single blood draw performed at the same time as the single neuroimaging encounter.
Presence and Level of Superoxide Dismutase (SOD)
Time frame: 1 day -Single blood draw performed at the same time as the single neuroimaging encounter.
Presence and Level of 8-isoprostane
Time frame: 1 day -Single blood draw performed at the same time as the single neuroimaging encounter.
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.
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.
Presence and Level of Catalase
Time frame: 1 day -Single blood draw performed at the same time as the single neuroimaging encounter.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Nov 2019.
- Background: PubMed 29111092Nestrasil 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.
- Background: PubMed 26095521Shapiro 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.
- Rare Diseases Clinical Research Network's web siteLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. De-identified individual data is input to the NIH-funded Rare Diseases Clinical Research Network's Data Management \& Coordinating Center ("DMCC"). Eventually this 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Igor Nestrasil, PhD, MD principal investigator
University of Minnesota
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Mucopolysaccharidosis Type I, run by University of Minnesota at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03576729, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Nov 2019.