Collection and Study of Cerebrospinal Fluid in Patients With Hunter Syndrome

• Sponsor: Shire (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01449240
• Collaborator: (none)
• Enrollment: 10
• Locations: 7
• Actual Duration (Months): 13.2
• Patients Per Site: 1.4
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hunter Syndrome	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 Design

• Study Type: Observational
• Actual Enrollment: 10 participants
• Observational Model: Case-Only
• Time Perspective: Prospective
• Official Title: A Cerebrospinal Fluid Collection Study in Pediatric and Adult Patients With Hunter Syndrome
• Actual Study Start Date: Nov 12, 2012
• Actual Primary Completion Date: Dec 20, 2013
• Actual Study Completion Date: Dec 20, 2013

Arms and Interventions

Arm	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

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 70 Years
• Sexes Eligible for Study: Male
• Accepts 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.

Contacts and Locations

Locations

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

Sponsors and Collaborators

• Shire

Investigators

• Study Director: Study Director, Takeda

Study Documents (Full-Text)

None provided.

More Information

Publications

• 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. Epub 2007 Feb 26.
• Dickson PI. Novel treatments and future perspectives: outcomes of intrathecal drug delivery. Int J Clin Pharmacol Ther. 2009;47 Suppl 1:S124-7. Review.
• 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.
• 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. Epub 2007 Nov 23. Review.

• Responsible Party: Shire
• ClinicalTrials.gov Identifier: NCT01449240
• Other Study ID Numbers: HGT-HIT-072
• First Posted: Oct 10, 2011
• Last Update Posted: Jun 9, 2021
• Last Verified: May 1, 2021

• Keywords provided by Shire: Hunter syndrome; Mucopolysaccharidosis II; Iduronate 2-Sulfatase Deficiency; Lumbar puncture; Cerebrospinal fluid (CSF); Pediatric; Adult; Biomarkers
• Additional relevant MeSH terms: Mucopolysaccharidosis II; Syndrome

Study Results

Participant Flow

Arm/Group Title	No Investigational Treatment or Control Group
Arm/Group Description	This was an observational study for the collection and study of cerebrospinal fluid (CSF) in patients with Hunter syndrome. No investigational treatment was given.
Period Title: Overall Study
STARTED	10
COMPLETED	10
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	No Investigational Treatment or Control Group
Arm/Group Description	This was an observational study for the collection and study of CSF in patients with Hunter syndrome. No investigational treatment was given.
Overall Participants	9
Age (Count of Participants)
<=18 years	4 44.4%
Between 18 and 65 years	5 55.6%
>=65 years	0 0%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	19.36
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	9 100%
Region of Enrollment (Count of Participants)
United States	8 88.9%
United Kingdom	1 11.1%

Outcome Measures

1. Primary Outcome

Title	Levels of Total Glycosaminoglycan (GAG) in CSF
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	No Investigational Treatment or Control Group
Arm/Group Description	This was an observational study for the collection and study of CSF in patients with Hunter syndrome. No investigational treatment was given.
Measure Participants	9
Mean (95% Confidence Interval) [ng/mL]	816.750

2. Secondary Outcome

Title	Levels of GAG in Urine
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	No Investigational Treatment or Control Group
Arm/Group Description	This was an observational study for the collection and study of CSF in patients with Hunter syndrome. No investigational treatment was given.
Measure Participants	8
Mean (95% Confidence Interval) [mg GAG/mmol Creatinine]	12.458

Adverse Events

Arm/Group Title	No Investigational Treatment or Control Group
Arm/Group Description	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.
All Cause Mortality
	No Investigational Treatment or Control Group
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	No Investigational Treatment or Control Group
	Affected / at Risk (%)	# Events
Total	1/9 (11.1%)
Nervous system disorders
Headache	1/9 (11.1%)	1
Other (Not Including Serious) Adverse Events
	No Investigational Treatment or Control Group
	Affected / at Risk (%)	# Events
Total	4/9 (44.4%)
Gastrointestinal disorders
Intermittent Lower Abdomen Spasms	1/9 (11.1%)	1
Injury, poisoning and procedural complications
Pain Secondary to Surgical Procedure	1/9 (11.1%)	1
Difficulty Hearing in Right Ear Secondary to Neurosurgery	1/9 (11.1%)	1
Intermittent Headaches Post-Neurosurgery	1/9 (11.1%)	1
Intermittent Soreness Post-Surgery	1/9 (11.1%)	1
Musculoskeletal and connective tissue disorders
Stiff Neck	1/9 (11.1%)	1
Nervous system disorders
Headache	1/9 (11.1%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.