MucopolysaccharidosesNCT01521429
Longitudinal Study of Bone Disease in Children with Mucopolysaccharidoses (MPS) I, II, and VI
An observational study of Mucopolysaccharidoses, run by Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center at 3 sites in United States.
Trial summary
Approximately 85% of individuals with Mucopolysaccharidosis (MPS) type I, II, or VI report weekly pain and 50-60% have significant limitations in their activities of daily living due to MPS related musculoskeletal disease despite treatment with enzyme replacement therapy (ERT). Read more about this study
- Who is it for?
- Ages 5 to 35 years
- Conditions the study is for
- Mucopolysaccharidoses
- How many people
- 55 participants
- Where
- 3 sitesUnited States
- Study dates
- Aug 2009to 31 Jul 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 5 to 35 years
- All sexes
- No healthy volunteers
- Child, Adult
Study population: community sample
Who may be able to join
- Diagnosis of MPS I, II, or VI
- Ability to travel to study center for evaluations.
- Age ≥ 5 years and < 35 years: age at entry into study must be ≥5 years and ≤33 years to ensure a minimum of 2 study visits.
Who cannot join
- Pregnancy (will be determined at each study visit)
- Participation in any other study within the past 12 months which would result in increasing the child's radiation exposure above 500 mrem for the calendar year.
- Participants who cannot comply with study procedures or have other factors that would inhibit their participation as determined by the PI's discretion.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
University of Minnesota
Minneapolis, Minnesota, 55454
Children's Hospital & Research Center Oakland
Oakland, California, 94609
Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
Torrance, California, 90502
About this study
Official title: Longitudinal Study of Bone and Endocrine Disease in Children with MPS I, II, and VI: a Multicenter Study of the Lysosomal Disease Network.
Approximately 85% of individuals with Mucopolysaccharidosis (MPS) type I, II, or VI report weekly pain and 50-60% have significant limitations in their activities of daily living due to MPS related musculoskeletal disease despite treatment with enzyme replacement therapy (ERT). Thus there is a critical need to identify additional therapies to alleviate the burden of musculoskeletal disease in order to improve the health and quality of life of individuals with MPS. However, disease progression needs to be quantified to be able to determine efficacy of new therapies. This study is a multi-institutional, 5-year, longitudinal study of musculoskeletal disease in MPS. The objective is to quantitatively describe the progression of skeletal disease and identify biomarkers that either predict disease severity or could be used as therapeutic targets in individuals with MPS I, II, and VI. A database of standardized measurements of musculoskeletal disease in MPS will allow the field to efficiently move forward with therapeutic clinical trials in patients with MPS.
Read the detailed description
Although children with MPS I, II, and VI who are treated with hematopoietic cell transplantation (HCT) and/or enzyme replacement therapy (ERT) are now living into adulthood with good cognitive development, their quality of life is significantly impacted by their skeletal abnormalities (i.e., kyphosis, scoliosis, genu valgum), joint contractures, pain, and severe short stature. Additional therapies (e.g., post-HCT supplemental ERT, anti-TNFα drugs, stop codon suppression drugs, gene therapy) to decrease the burden of skeletal disease and improve growth are needed. However, prior to these therapeutic studies, control data quantifying the progression of skeletal disease in individuals with MPS I, II and VI treated with ERT and/or HCT are needed, along with biomarkers to be used as early predictors of response to treatment.
Osteoporosis has been described in animal models of MPS. It is unknown whether abnormalities seen in animal models of MPS can be extrapolated to osteoporosis or increased risk of fracture in children and adults affected with MPS. Preliminary data suggest that children and adolescents with MPS I, II and VI have low bone mineral density (BMD) after adjustment for short stature and abnormal bone geometry and that markers of bone remodeling are cross-sectionally associated with BMD. It is unknown whether this decreased BMD during childhood will result in osteoporosis and increased fracture risk in adulthood. Determining the risk for osteoporosis in MPS I, II and VI has become particularly important as these individuals are now healthier and more mobile with new and improved treatments and thus have a greater opportunity for fracture.
Glycosaminoglycan (GAG) deposition has been identified in bone and cartilage in animal models of MPS. GAG deposition in cartilage has specifically been shown to induce inflammation (e.g. increased tumor necrosis-alpha [TNF- α ] levels in serum and synovial fluid), chondrocyte apoptosis, and hyperplasia of the synovial membranes. We have found that serum TNF-α is elevated in children and adolescents with MPS I, II and VI and is associated with bodily pain and poor physical function.
Our long-term goal is to identify and test new therapies for musculoskeletal disease in MPS. The objective of this proposed longitudinal observational study is to document the progression of skeletal disease and identify biomarkers that either predict disease severity or could be used as therapeutic targets in individuals with MPS I, II, and VI. The rationale for this project is to obtain baseline data for future therapeutic clinical trials and to identify potential therapeutic targets. Our central hypothesis is that skeletal disease will progress over time and that biomarkers of inflammation, and bone and cartilage turnover, will predict the severity of skeletal disease over time. Therefore, this study has the following specific aims (SA):
SA1: To characterize the progression of skeletal disease from childhood into young adulthood for individuals with MPS I, II and VI. Our hypothesis is that there will be a progressive decrease in bone health as this population matures into young adulthood due to decreasing mobility, chronic inflammation, and intrinsic MPS related bone disease.
SA2: To identify prognostic biomarkers of inflammation, bone remodeling, and cartilage turnover that can predict the progression of skeletal disease and impaired physical function in MPS I, II and VI. Our hypothesis is that biomarkers of inflammation, bone remodeling, and cartilage turnover, will be predictive of change in physical function, BMD, range of motion, hip dysplasia, kyphoscoliosis, quality of life, and height over 5 years.
At the completion of this study we expect to quantify the progression of skeletal disease in MPS I, II and VI treated with ERT and/or HCT to be used in future therapeutic clinical trials. In addition, we will obtain biomarkers of skeletal disease progression that could identify early treatment efficacy. Finally, we will gain further insight into the mechanism of persistent skeletal disease in MPS that will provide potential therapeutic targets.
- Conditions
- Mucopolysaccharidoses
- Medical subject headings
- Mucopolysaccharidoses
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 |
|---|---|---|
| MPS I | Mucopolysaccharidosis I (Hurler, Scheie, Hurler-Scheie) | |
| MPS II | Mucopolysaccharidosis II (Hunter) | |
| MPS VI | Mucopolysaccharidosis VI (Maroteaux-Lamy) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Annual change in dual energy x-ray absorptiometry (DXA)
Measurement of bone density and body composition
Measured: baseline, year 1, year 2, year 3
Secondary outcomes (5)
Annual change in Peripheral quantitative computer tomography (pQCT)
Measurement of volumetric bone density, bone geometry, bone strength, and muscle fat
Measured: baseline, year 1, year 2, year 3
Annual change in Biomarkers of bone remodeling
Measurements of bone turnover
Measured: baseline, year 1, year 2, year 3
Annual change in Biodex
Measurement of muscle strength
Measured: baseline, year 1, year 2, year 3
Annual change in Endocrine function tests
Thyroid function, growth factor levels, pubertal hormones, vitamin D
Measured: baseline, year 1, year 2, year 3
Annual change in growth measurements
sitting and standing heights, arm and tibial length
Measured: baseline, year 1, year 2, year 3
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2012 (estimated)
- Study startAug 2009
- Primary completion31 Jul 2019
- Study completion31 Jul 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MucopolysaccharidosesStudies of the same condition, open and under way.
- 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 55 participants (actual)
Sponsor and investigators
- Lead sponsor
- Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Rare Diseases Clinical Research Network, National Institute of Neurological Disorders and Stroke (NINDS), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), UCSF Benioff Children's Hospital Oakland, National Center for Advancing Translational Sciences (NCATS)
- Responsible party
- Principal investigator, Lynda E Polgreen, Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
- Investigators
- Lynda E Polgreen, MD, MS, Principal investigator, Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01521429
- Sponsor's protocol ID
- 0906M68810
- Other IDs
- U54NS065768
- Status last verified
- Nov 2019
- First submitted
- 11 Nov 2011
- Last updated
- 22 Oct 2024
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Longitudinal Study of Bone and Endocrine Disease in Children with MPS I, II, and VI: a Multicenter Study of the Lysosomal Disease Network.
- ClinicalTrials.gov ID
- NCT01521429
- Acronym / sponsor ID
- 0906M68810
- Conditions
- Mucopolysaccharidoses
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 55 participants (actual)
- Lead sponsor
- Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical CenterUniversity, hospital or other
- Collaborators
- Rare Diseases Clinical Research Network, National Institute of Neurological Disorders and Stroke (NINDS), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), UCSF Benioff Children's Hospital Oakland, National Center for Advancing Translational Sciences (NCATS)
- Study start
- Aug 2009
- Primary completion
- 31 Jul 2019 (actual)
- Study completion
- 31 Jul 2019 (actual)
- First posted
- 30 Jan 2012 (estimated)
- 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.
Approximately 85% of individuals with Mucopolysaccharidosis (MPS) type I, II, or VI report weekly pain and 50-60% have significant limitations in their activities of daily living due to MPS related musculoskeletal disease despite treatment with enzyme replacement therapy (ERT). Thus there is a critical need to identify additional therapies to alleviate the burden of musculoskeletal disease in order to improve the health and quality of life of individuals with MPS. However, disease progression needs to be quantified to be able to determine efficacy of new therapies. This study is a multi-institutional, 5-year, longitudinal study of musculoskeletal disease in MPS. The objective is to quantitatively describe the progression of skeletal disease and identify biomarkers that either predict disease severity or could be used as therapeutic targets in individuals with MPS I, II, and VI. A database of standardized measurements of musculoskeletal disease in MPS will allow the field to efficiently move forward with therapeutic clinical trials in patients with MPS.
Detailed description
Although children with MPS I, II, and VI who are treated with hematopoietic cell transplantation (HCT) and/or enzyme replacement therapy (ERT) are now living into adulthood with good cognitive development, their quality of life is significantly impacted by their skeletal abnormalities (i.e., kyphosis, scoliosis, genu valgum), joint contractures, pain, and severe short stature. Additional therapies (e.g., post-HCT supplemental ERT, anti-TNFα drugs, stop codon suppression drugs, gene therapy) to decrease the burden of skeletal disease and improve growth are needed. However, prior to these therapeutic studies, control data quantifying the progression of skeletal disease in individuals with MPS I, II and VI treated with ERT and/or HCT are needed, along with biomarkers to be used as early predictors of response to treatment.
Osteoporosis has been described in animal models of MPS. It is unknown whether abnormalities seen in animal models of MPS can be extrapolated to osteoporosis or increased risk of fracture in children and adults affected with MPS. Preliminary data suggest that children and adolescents with MPS I, II and VI have low bone mineral density (BMD) after adjustment for short stature and abnormal bone geometry and that markers of bone remodeling are cross-sectionally associated with BMD. It is unknown whether this decreased BMD during childhood will result in osteoporosis and increased fracture risk in adulthood. Determining the risk for osteoporosis in MPS I, II and VI has become particularly important as these individuals are now healthier and more mobile with new and improved treatments and thus have a greater opportunity for fracture.
Glycosaminoglycan (GAG) deposition has been identified in bone and cartilage in animal models of MPS. GAG deposition in cartilage has specifically been shown to induce inflammation (e.g. increased tumor necrosis-alpha [TNF- α ] levels in serum and synovial fluid), chondrocyte apoptosis, and hyperplasia of the synovial membranes. We have found that serum TNF-α is elevated in children and adolescents with MPS I, II and VI and is associated with bodily pain and poor physical function.
Our long-term goal is to identify and test new therapies for musculoskeletal disease in MPS. The objective of this proposed longitudinal observational study is to document the progression of skeletal disease and identify biomarkers that either predict disease severity or could be used as therapeutic targets in individuals with MPS I, II, and VI. The rationale for this project is to obtain baseline data for future therapeutic clinical trials and to identify potential therapeutic targets. Our central hypothesis is that skeletal disease will progress over time and that biomarkers of inflammation, and bone and cartilage turnover, will predict the severity of skeletal disease over time. Therefore, this study has the following specific aims (SA):
SA1: To characterize the progression of skeletal disease from childhood into young adulthood for individuals with MPS I, II and VI. Our hypothesis is that there will be a progressive decrease in bone health as this population matures into young adulthood due to decreasing mobility, chronic inflammation, and intrinsic MPS related bone disease.
SA2: To identify prognostic biomarkers of inflammation, bone remodeling, and cartilage turnover that can predict the progression of skeletal disease and impaired physical function in MPS I, II and VI. Our hypothesis is that biomarkers of inflammation, bone remodeling, and cartilage turnover, will be predictive of change in physical function, BMD, range of motion, hip dysplasia, kyphoscoliosis, quality of life, and height over 5 years.
At the completion of this study we expect to quantify the progression of skeletal disease in MPS I, II and VI treated with ERT and/or HCT to be used in future therapeutic clinical trials. In addition, we will obtain biomarkers of skeletal disease progression that could identify early treatment efficacy. Finally, we will gain further insight into the mechanism of persistent skeletal disease in MPS that will provide potential therapeutic targets.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| MPS I | – | –Mucopolysaccharidosis I (Hurler, Scheie, Hurler-Scheie) |
| MPS II | – | –Mucopolysaccharidosis II (Hunter) |
| MPS VI | – | –Mucopolysaccharidosis VI (Maroteaux-Lamy) |
Who may qualify
- Ages
- 5 to 35 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- Study population
- community sample
Key inclusion criteria (3 listed)
- Diagnosis of MPS I, II, or VI
- Ability to travel to study center for evaluations.
- Age ≥ 5 years and < 35 years: age at entry into study must be ≥5 years and ≤33 years to ensure a minimum of 2 study visits.
Key exclusion criteria (3 listed)
- Pregnancy (will be determined at each study visit)
- Participation in any other study within the past 12 months which would result in increasing the child's radiation exposure above 500 mrem for the calendar year.
- Participants who cannot comply with study procedures or have other factors that would inhibit their participation as determined by the PI's discretion.
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
Annual change in dual energy x-ray absorptiometry (DXA)
Time frame: baseline, year 1, year 2, year 3
Measurement of bone density and body composition
5 secondary outcomes
Annual change in Peripheral quantitative computer tomography (pQCT)
Time frame: baseline, year 1, year 2, year 3
Annual change in Biomarkers of bone remodeling
Time frame: baseline, year 1, year 2, year 3
Annual change in Biodex
Time frame: baseline, year 1, year 2, year 3
Annual change in Endocrine function tests
Time frame: baseline, year 1, year 2, year 3
Annual change in growth measurements
Time frame: baseline, year 1, year 2, year 3
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 22 Oct 2024.
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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.
Lynda E Polgreen, MD, MS principal investigator
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Mucopolysaccharidoses, run by Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center at 3 sites 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 3 inclusion and 3 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 22 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites 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?
Annual change in dual energy x-ray absorptiometry (DXA) (time frame: baseline, year 1, year 2, year 3). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 22 Oct 2024.