Hunter Syndrome
Conditions
Keywords
Hunter syndrome, Mucopolysaccharidosis II, Iduronate 2-Sulfatase Deficiency, Lumbar puncture, Cerebrospinal fluid (CSF), Pediatric, Adult, Biomarkers
Brief summary
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.
Detailed description
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.
Interventions
OTHERNo treatment
Sponsors
Shire
Study design
Observational model
CASE_ONLY
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
MALE
Age
No minimum to 70 Years
Healthy volunteers
No
Inclusion criteria
* The patient is male and has a documented diagnosis of Hunter syndrome (MPSII). * The adult patient has completed a cognitive assessment at screening/baseline or within the previous 3 months and has been determined to have an intelligence quotient (IQ) ≥78. Note: cognitive evaluation of pediatric patients is not required. * The adult patient or the adult patient's legally authorized representative(s) has voluntarily signed an Institutional Review Board/Independent Ethics Committee-approved informed consent form after all relevant aspects of the study have been explained and discussed. * The pediatric patient must be scheduled to undergo a non-study related lumbar puncture or other medical or diagnostic procedure that requires the administration of general anesthesia. The pediatric patient's parent(s) or legally authorized representative(s) must have provided written informed consent (with patient assent as relevant), after all relevant aspects of the study have been explained and discussed, to allow CSF sample collection for this study in conjunction with performance of the non-study related procedure requiring general anesthesia.
Exclusion criteria
* The patient has a history of complications from a previous lumbar puncture(s) or technical challenges in conducting lumbar puncture. * The patient has received a hematopoietic stem cell transplant. * The patient has taken aspirin, non-steroidal anti-inflammatory drugs (NSAIDs), or other over-the-counter or prescription medications that could affect blood clot formation within the 7 days prior to lumbar puncture, or has ingested such medications within 7 days prior to any study-related procedure in which a change in potential blood clot formation would be deleterious. * The patient is currently receiving treatment with intrathecal idursulfase-IT. * The patient is currently enrolled in an interventional clinical trial. * The patient has participated in a clinical trial of any investigational drug, including idursulfase-IT, or device within the 30 days prior to study entry.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Levels of Total Glycosaminoglycan (GAG) in CSF | Day 1 | The concentration of total GAG, including heparan sulfate (HS) and dermatan sulfate (DS) oligosaccharides, in CSF was measured using an enzymatic assay. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Levels of GAG in Urine | Day 1 | 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. |
Countries
United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 9 |
| Total | 9 |
Baseline characteristics
| Characteristic | No Investigational Treatment or Control Group |
|---|---|
| Age, Categorical <=18 years | 4 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants |
| Age, Continuous | 19.36 years |
| Region of Enrollment United Kingdom | 1 Participants |
| Region of Enrollment United States | 8 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 4 / 9 |
| serious Total, serious adverse events | 1 / 9 |
Outcome results
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.
Time frame: Day 1
Population: 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.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| No Investigational Treatment or Control Group | Levels of Total Glycosaminoglycan (GAG) in CSF | 816.750 ng/mL |
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.
Time frame: Day 1
Population: 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.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| No Investigational Treatment or Control Group | Levels of GAG in Urine | 12.458 mg GAG/mmol Creatinine |