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The purpose of the study is to collect data on CSF biomarkers in patients with Hunter Syndrome that would serve as reference data for comparison with cognitively impaired patients with Hunter syndrome, patients with other lysosomal storage diseases, or other diseases with CNS involvement.
To determine levels of glycosaminoglycans (GAGs), including dermatan sulfate (DS) and heparan sulfate (HS), GAG-degradation products, and other biomarkers of central nervous system (CNS) and lysosomal function in cerebrospinal fluid (CSF) in pediatric and adult patients with Hunter syndrome.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| No treatment | Approximately 5 adults (equal to or not less than 18yrs old) and 5 children (equal to or not over 18yrs old) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| No treatment | Other |
|
| Measure | Description | Time Frame |
|---|---|---|
| Levels of Total Glycosaminoglycan (GAG) in CSF | The concentration of total GAG, including heparan sulfate (HS) and dermatan sulfate (DS) oligosaccharides, in CSF was measured using an enzymatic assay. | Day 1 |
| Measure | Description | Time Frame |
|---|---|---|
| Levels of GAG in Urine | The levels of GAG (including sulfated DS/HS oligosaccharides) in urine were determined by the Blyscan sulfated GAG assay kit. The concentration of GAG in urine was normalized to the urine creatinine value and reported as mg GAG/mmol creatinine. | Day 1 |
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Inclusion Criteria:
Exclusion Criteria:
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The study population will consist of pediatric (<18 years of age) and adult (≥18 years of age) male patients with Hunter syndrome. Up to approximately 60 patients (approximately 30 adults and 30 children) may be enrolled in this study.
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| Name | Affiliation | Role |
|---|---|---|
| Study Director | Takeda | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Emory University | Decatur | Georgia | 30033 | United States | ||
| Ann & Robert H. Lurie Children's Hospital of Chicago |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 18038146 | Background | Wraith JE, Scarpa M, Beck M, Bodamer OA, De Meirleir L, Guffon N, Meldgaard Lund A, Malm G, Van der Ploeg AT, Zeman J. Mucopolysaccharidosis type II (Hunter syndrome): a clinical review and recommendations for treatment in the era of enzyme replacement therapy. Eur J Pediatr. 2008 Mar;167(3):267-77. doi: 10.1007/s00431-007-0635-4. Epub 2007 Nov 23. | |
| 20040323 |
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| ID | Title | Description |
|---|---|---|
| FG000 | No Investigational Treatment or Control Group | This was an observational study for the collection and study of cerebrospinal fluid (CSF) in patients with Hunter syndrome. No investigational treatment was given. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Safety Population: All patients who had undergone a procedure for CSF sample collection. This included a patient who underwent unsuccessful CSF sample collection. It did not include a patient who provided a retrospective CSF sample.
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| ID | Title | Description |
|---|---|---|
| BG000 | No Investigational Treatment or Control Group | This was an observational study for the collection and study of CSF in patients with Hunter syndrome. No investigational treatment was given. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Age (years) at CSF sample collection |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Levels of Total Glycosaminoglycan (GAG) in CSF | The concentration of total GAG, including heparan sulfate (HS) and dermatan sulfate (DS) oligosaccharides, in CSF was measured using an enzymatic assay. | Pharmacodynamic Population: All patients for which an evaluable CSF sample was collected. This included a pediatric patient who was consented to provide a retrospective CSF sample. | Posted | Mean | 95% Confidence Interval | ng/mL | Day 1 |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | No Investigational Treatment or Control Group | This was an observational study for the collection and study of CSF in patients with Hunter syndrome. No investigational treatment was given. Safety analyses were performed in the Safety Population, which was defined as all patients who had undergone a procedure for CSF sample collection. This included a patient who underwent unsuccessful CSF sample collection; no CSF or urine GAG data were available for this adult patient. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | Nervous system disorders |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Stiff Neck | Musculoskeletal and connective tissue disorders |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Shire | +1 866 842 5335 | ClinicalTransparency@shire.com |
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| ID | Term |
|---|---|
| D016532 | Mucopolysaccharidosis II |
| ID | Term |
|---|---|
| D038901 | X-Linked Intellectual Disability |
| D008607 | Intellectual Disability |
| D019954 | Neurobehavioral Manifestations |
| D009461 | Neurologic Manifestations |
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CSF and urine samples will be retained and analyzed for glycosaminoglycans (GAGs), including sulfated DS/HS oligosaccharides, GAG-degradation products, and other biomarkers of CNS or lysosomal function.
| Chicago |
| Illinois |
| 60611-2605 |
| United States |
| Children's Hospitals and Clinics of Minnesota | Minneapolis | Minnesota | 55404 | United States |
| University of North Carolina, Division of Genetics and Metabolism | Chapel Hill | North Carolina | 27599 | United States |
| University of Utah School of Medicine | Salt Lake City | Utah | 84113 | United States |
| Central Manchester University Hospitals NHS Foundation Trust, St. Mary's Hospital | Manchester | M13 9WL | United Kingdom |
| Salford Royal NHS Foundation Trust | Salford | M6 8HD | United Kingdom |
| Dickson PI. Novel treatments and future perspectives: outcomes of intrathecal drug delivery. Int J Clin Pharmacol Ther. 2009;47 Suppl 1:S124-7. |
| 17321776 | Background | Dickson P, McEntee M, Vogler C, Le S, Levy B, Peinovich M, Hanson S, Passage M, Kakkis E. Intrathecal enzyme replacement therapy: successful treatment of brain disease via the cerebrospinal fluid. Mol Genet Metab. 2007 May;91(1):61-8. doi: 10.1016/j.ymgme.2006.12.012. Epub 2007 Feb 26. |
| Background | Christian J. Hendriksz, Joseph Muenzer, Barbara K. Burton, Luying Pan, Nan Wang, Hicham Naimy, Arian Pano, and Ann J. Barbier. A Cerebrospinal Fluid Collection Study in Pediatric and Adult Patients With Hunter Syndrome. Journal of Inborn Errors of Metabolism & Screening, January 2015; vol. 3 |
| Count of Participants |
| Participants |
|
| Age, Continuous | Age (years) at CSF sample collection | Mean | Full Range | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| Units |
|---|
| Counts |
|---|
| Participants |
|
|
| Secondary | Levels of GAG in Urine | The levels of GAG (including sulfated DS/HS oligosaccharides) in urine were determined by the Blyscan sulfated GAG assay kit. The concentration of GAG in urine was normalized to the urine creatinine value and reported as mg GAG/mmol creatinine. | Pharmacodynamic Population: All patients for which an evaluable CSF sample was collected. Urinary GAG was not measured in 2 patients: 1 pediatric patient who provided a retrospective CSF sample only (no urine sample was collected) and 1 adult patient whose CSF sample was not considered evaluable and therefore their urinary GAG was not measured. | Posted | Mean | 95% Confidence Interval | mg GAG/mmol Creatinine | Day 1 |
|
|
|
| 1 |
| 9 |
| 4 |
| 9 |
| Headache | Nervous system disorders |
|
| Pain Secondary to Surgical Procedure | Injury, poisoning and procedural complications |
|
| Difficulty Hearing in Right Ear Secondary to Neurosurgery | Injury, poisoning and procedural complications |
|
| Intermittent Headaches Post-Neurosurgery | Injury, poisoning and procedural complications |
|
| Intermittent Lower Abdomen Spasms | Gastrointestinal disorders |
|
| Intermittent Soreness Post-Surgery | Injury, poisoning and procedural complications |
|
If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.
| D009422 | Nervous System Diseases |
| D040181 | Genetic Diseases, X-Linked |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D020271 | Heredodegenerative Disorders, Nervous System |
| D009083 | Mucopolysaccharidoses |
| D002239 | Carbohydrate Metabolism, Inborn Errors |
| D008661 | Metabolism, Inborn Errors |
| D016464 | Lysosomal Storage Diseases |
| D017520 | Mucinoses |
| D003240 | Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |