Study to Detect Unrecognized Mucopolysaccharidosis in Children Visiting Rheumatology, Hand or Skeletal Dysplasia Clinics

This study has been terminated.
(Funding withdrawn due to insufficient enrollment rate)
Sponsor:
Collaborator:
MediResource Inc.
Information provided by (Responsible Party):
National MPS Society
ClinicalTrials.gov Identifier:
NCT01675674
First received: August 23, 2012
Last updated: May 23, 2013
Last verified: May 2013
  Purpose

This study is being done to learn how many children and young adults who come to pediatric rheumatology clinics may have mucopolysaccharidosis (MPS). The study tests for 4 of the types of MPS: I, II, IVA, and VI. This can help researchers decide whether to create a screening program for MPS at pediatric rheumatology clinics. This study is being done in rheumatology clinics because the first symptoms of MPS are often joint problems such as stiff joints, and rheumatologists may be the first doctors that a patient with MPS visits. The study will also evaluate the utility of dried blood spot testing for MPS.


Condition Intervention
Mucopolysaccharidoses
Mucopolysaccharidosis I
Mucopolysaccharidosis II
Mucopolysaccharidosis IV
Mucopolysaccharidosis VI
Other: Dried blood spot test for MPS

Study Type: Observational
Official Title: Unrecognized Mucopolysaccharidosis I, II, IVA, and VI in the Pediatric Rheumatology Population

Resource links provided by NLM:


Further study details as provided by National MPS Society:

Primary Outcome Measures:
  • Incidence of previously unrecognized MPS I, II, IVA, and VI in children presenting to pediatric rheumatology, hand, or skeletal dysplasia clinics [ Time Frame: At study completion (approximately 18 months after the beginning of the study) ] [ Designated as safety issue: No ]
    Each patient is screened for MPS I, II, IVA, and VI after enrolling in the study. The results for all patients will be pooled when the study is completed (expected completion approx. 18 months after the study begins).


Secondary Outcome Measures:
  • Utility of DBS testing to screen for MPS in pediatric patients [ Time Frame: At study completion (approximately 18 months after the beginning of the study) ] [ Designated as safety issue: Yes ]

    For the secondary endpoint (utility of DBS testing), the following data will be collected: ease of taking and sending the DBS sample; number of errors of sample taking; adverse events (if any) associated with blood sampling by finger prick or venipuncture (for subjects over one year of age; choose whichever method is most convenient) or heel prick (for subjects under one year of age); and comfort of patients and/or their parents with the test.

    Study personnel who performed DBS testing will also be asked to complete a brief survey about the utility of DBS testing.



Estimated Enrollment: 3000
Study Start Date: September 2011
Estimated Study Completion Date: March 2014
Estimated Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Dried blood spot test for MPS

For the prospective study, subjects will be drawn from all children (aged 6 months to 18 years) with a history of presenting to selected clinics (pediatric rheumatology, pediatric hand, or skeletal dysplasia clinic), with at least ONE "highly suspicious" symptom or at least TWO "less suspicious" symptoms that may be indicative of an MPS disorder (see inclusion criteria).

For the retrospective chart review, subjects will be drawn from all children who were 6 months to 18 years of age at the time of first presentation to selected clinics (pediatric rheumatology, pediatric hand, or skeletal dysplasia clinic), with at least ONE "highly suspicious" symptom or at least TWO "less suspicious" symptoms that may be indicative of an MPS disorder (see inclusion criteria).

Other: Dried blood spot test for MPS
The dried blood spot test uses a few drops of blood on filter paper to screen for mucopolysaccharidoses (MPS I, MPS II, MPS IVA and MPS VI in this study).
Other Name: DBS testing

Detailed Description:

MPS, or mucopolysaccharidosis (mew-co-paw-lee-sack-a-rid-o-sis), disorders are a group of rare inherited diseases that affect about 1 in every 25,000 people in the United States. There are 7 MPS disorders: MPS I (Hurler, Hurler-Scheie, and Scheie syndromes), II (Hunter syndrome), III (Sanfilippo syndrome), IV (Morquio syndrome), VI (Maroteaux-Lamy syndrome), VII (Sly syndrome), and IX (no other name). In people who have MPS, the body cannot break down certain materials in the body's cells. These materials then build up in the cells, causing problems such as stiff joints, misshapen bones, curled hands and reduced hand function, frequent ear infections, vision and hearing problems, "thickened" facial features, and heart problems. Getting access to diagnosis and treatment can help make MPS easier to manage; but unfortunately, people with MPS may go undiagnosed for many years.

This study is being done to learn how many children and young adults who come to pediatric rheumatology clinics may have mucopolysaccharidosis (MPS). The study tests for 4 of the types of MPS: I, II, IVA, and VI. This can help researchers decide whether to create a screening program for MPS at pediatric rheumatology clinics. This study is being done in rheumatology clinics because the first symptoms of MPS are often joint problems such as stiff joints, and rheumatologists may be the first doctors that a patient with MPS visits.

The study will use dried blood spot (DBS) testing to screen for these types of MPS. It will also use a survey to evaluate the utility and convenience of dried blood spot testing for MPS.

  Eligibility

Ages Eligible for Study:   6 Months to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

For the prospective study, subjects will be drawn from all children (aged 6 months to 18 years) with a history of presenting to selected clinics (pediatric rheumatology, pediatric hand, or skeletal dysplasia clinic), with at least ONE "highly suspicious" symptom or at least TWO "less suspicious" symptoms that may be indicative of an MPS disorder (see inclusion criteria).

For the retrospective chart review, subjects will be drawn from all children who were 6 months to 18 years of age at the time of first presentation to selected clinics (pediatric rheumatology, pediatric hand, or skeletal dysplasia clinic), with at least ONE "highly suspicious" symptom or at least TWO "less suspicious" symptoms that may be indicative of an MPS disorder (see inclusion criteria).

Criteria

Inclusion Criteria:

  1. History of presenting to the pediatric rheumatology, pediatric hand, or skeletal dysplasia clinic with at least ONE "highly suspicious" symptom or at least TWO "less suspicious" symptoms that may be indicative of an MPS disorder (see below):

    Highly suspicious symptoms:

    • characteristic facial features
    • hearing loss
    • corneal clouding
    • cardiac manifestations
    • dysostosis multiplex
    • hepatosplenomegaly
    • spinal cord compression
    • hydrocephalus
    • carpal tunnel syndrome
    • delayed mental development or regression in mental development

    Less suspicious symptoms:

    • short stature
    • extensive Mongolian spots
    • sleep apnea
    • copious nasal discharge
    • recurrent otitis media, ear fluid that will not drain, or the presence of ear tubes
    • frequent upper respiratory tract infections
    • joint stiffness or limited range of motion
    • hand problems (Claw hands or reduced hand function)
    • hernia (inguinal or umbilical)
    • abnormally shaped teeth
    • dental cysts
    • tooth abscess
  2. Age of at least 6 months.
  3. Age under 18 years at time of initial clinic presentation.
  4. Written, signed, and dated informed consent obtained from the subject (if 18 years of age) or the subject's parents (if under 18). Written, dated, and signed assent from children is also required at some centers.

Exclusion Criteria:

  1. Under 6 months of age.
  2. Over 18 years of age at initial clinic presentation.
  3. Patients who have had confirmation of an MPS disorder by biochemical analysis and/or by molecular biology.
  4. Patients for whom MPS enzyme activity tests (i.e., enzyme levels tested in fibroblasts, leukocytes, serum, or blood spots) have already been performed, and for which the result was normal. (Patients who have been screened for MPS through urinary GAG and tested normal will not be excluded from the study.)
  5. Written informed consent not available.
  6. Subject unwilling or unable to provide the necessary blood spot for analysis.
  7. Any other condition that would, in the opinion of the investigator, interfere with the participant's ability to provide informed consent, comply with study instructions, or possibly confound interpretation of study results.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01675674

Locations
United States, New Jersey
University of Medicine and Dentistry of New Jersey
New Brunswick, New Jersey, United States, 08901
United States, New York
Hospital for Special Surgery
New York, New York, United States, 10021
Sponsors and Collaborators
National MPS Society
MediResource Inc.
Investigators
Principal Investigator: Thomas JA Lehman, MD Chief, Division of Pediatric Rheumatology, Hospital for Special Surgery; Professor of Clinical Pediatrics, Cornell University
  More Information

Publications:

Responsible Party: National MPS Society
ClinicalTrials.gov Identifier: NCT01675674     History of Changes
Other Study ID Numbers: RHE-001
Study First Received: August 23, 2012
Last Updated: May 23, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by National MPS Society:
Mucopolysaccharidoses
Prevalence
Pediatric
Rheumatology
Mucopolysaccharidosis I
Mucopolysaccharidosis II
Mucopolysaccharidosis IV
Mucopolysaccharidosis VI

Additional relevant MeSH terms:
Mucopolysaccharidoses
Mucopolysaccharidosis I
Mucopolysaccharidosis VI
Mucopolysaccharidosis II
Mucopolysaccharidosis IV
Osteochondrodysplasias
Carbohydrate Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Lysosomal Storage Diseases
Mucinoses
Connective Tissue Diseases
Metabolic Diseases
Mental Retardation, X-Linked
Intellectual Disability
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Genetic Diseases, X-Linked
Heredodegenerative Disorders, Nervous System
Bone Diseases, Developmental
Bone Diseases
Musculoskeletal Diseases

ClinicalTrials.gov processed this record on September 30, 2014