Collection and Study of Cerebrospinal Fluid in Patients With Hunter Syndrome

A Cerebrospinal Fluid Collection Study in Pediatric and Adult Patients With Hunter Syndrome

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.

Study Overview

• Status: Completed
• Conditions: Hunter Syndrome
• Intervention / Treatment: Other: No treatment

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.

• Study Type: Observational
• Enrollment (Actual): 10

Contacts and Locations

Study Locations

• United Kingdom
  • Manchester, United Kingdom, M13 9WL
    • Central Manchester University Hospitals NHS Foundation Trust, St. Mary's Hospital
  • Salford, United Kingdom, M6 8HD
    • Salford Royal NHS Foundation Trust
• United States
  • Georgia
    • Decatur, Georgia, United States, 30033
      • Emory University
  • Illinois
    • Chicago, Illinois, United States, 60611-2605
      • Ann & Robert H. Lurie Children's Hospital of Chicago
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • Children's Hospitals and Clinics of Minnesota
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina, Division of Genetics and Metabolism
  • Utah
    • Salt Lake City, Utah, United States, 84113
      • University of Utah School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 70 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

• Sampling Method: Non-Probability Sample

Study Population

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.

Description

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
No treatment; Approximately 5 adults (equal to or not less than 18yrs old) and 5 children (equal to or not over 18yrs old)	Other: No treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Shire

Publications and helpful links

General Publications

• 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.
• Dickson PI. Novel treatments and future perspectives: outcomes of intrathecal drug delivery. Int J Clin Pharmacol Ther. 2009;47 Suppl 1:S124-7.
• 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.
• Hendriksz CJ, Muenzer J, Vanderver A, Davis JM, Burton BK, Mendelsohn NJ, Wang N, Pan L, Pano A, Barbier AJ. Levels of glycosaminoglycans in the cerebrospinal fluid of healthy young adults, surrogate-normal children, and Hunter syndrome patients with and without cognitive impairment. Mol Genet Metab Rep. 2015 Nov 9;5:103-106. doi: 10.1016/j.ymgmr.2015.11.001. eCollection 2015 Dec.

Study record dates

Study Major Dates

• Study Start (Actual): November 12, 2012
• Primary Completion (Actual): December 20, 2013
• Study Completion (Actual): December 20, 2013

Study Registration Dates

• First Submitted: October 6, 2011
• First Submitted That Met QC Criteria: October 7, 2011
• First Posted (Estimate): October 10, 2011

Study Record Updates

• Last Update Posted (Actual): June 9, 2021
• Last Update Submitted That Met QC Criteria: May 24, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Mucopolysaccharidosis II; Pediatric; Adult; Biomarkers; Lumbar puncture; Hunter syndrome; Iduronate 2-Sulfatase Deficiency; Cerebrospinal fluid (CSF)
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Disease; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Connective Tissue Diseases; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Mucinoses; Mental Retardation, X-Linked; Intellectual Disability; Heredodegenerative Disorders, Nervous System; Mucopolysaccharidoses; Syndrome; Mucopolysaccharidosis II
• Other Study ID Numbers: HGT-HIT-072