Intrathecal Enzyme Replacement for Hurler Syndrome - Full Text View

Purpose

This protocol will examine whether the enzyme -L-iduronidase, delivered into the spinal fluid of patients with Hurler syndrome at intervals before and after bone marrow transplant, is a safe and effective approach to slow the neurologic degeneration seen in Hurler patients undergoing transplantation.

Condition	Intervention	Phase
MPS IH (Hurler Syndrome)	Drug: IRT Laronidase	Phase II

ChemIDplus related topics:

Laronidase

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study

Official Title:	Intrathecal Enzyme Replacement Therapy For Patients With Mucopolysaccharidosis Type I (Hurler Syndrome)

Further study details as provided by University of Minnesota:

Primary Outcome Measures:

To demonstrate the efficacy of intrathecally delivering alpha-L-iduronidase in patients with mucopolysaccharidosis type I in decreasing neurodevelopmental deterioration [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

To determine the safety and toxicity of intrathecally delivering alpha-L-iduronidase in patients with mucopolysaccharidosis type I [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
To determine brain changes with magnetic resonance imaging [ Time Frame: 1 and 2 years ] [ Designated as safety issue: No ]
To determine neurocognitive changes present in patients with Hurler syndrome [ Time Frame: 6, 12, and 24 months ] [ Designated as safety issue: No ]
To evaluate memory/encoding [ Time Frame: 12 and 24 months after hematopoietic stem cell transplantation ] [ Designated as safety issue: No ]
To determine cerebral spinal fluid levels of glycosaminoglycans, cytokines and antibodies to Laronidase at baseline and at each point CSF is obtained [ Time Frame: through 1 year ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	25
Study Start Date:	December 2007
Estimated Study Completion Date:	December 2014
Estimated Primary Completion Date:	December 2012 (Final data collection date for primary outcome measure)

Intervention Details:

Laronidase belongs to a class of drugs called enzyme replacement therapies or ERT that provides people with sufficient quantities of an important enzyme that they cannot create on their own. The main ingredient in laronidase is a protein that is identical to a naturally occurring form of the human enzyme alpha-L-iduronidase. Laronidase replaces the missing enzyme alpha-L-iduronidase and restores sufficient enzyme activity to break down GAG buildup.

Subjects will receive an infusion of Laronidase into his/her spinal fluid approximately 12 weeks before, 2 weeks before, 100 days after and 6 months after transplant. This procedure is done by lumbar puncture

Detailed Description:

Subjects will receive an infusion of Laronidase into his/her spinal fluid approximately 12 weeks before, 2 weeks before, 100 days after and 6 months after transplant (performed on another study protocol). This procedure is done by lumbar puncture (also called a "spinal tap").

Eligibility

Ages Eligible for Study:	8 Months to 3 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patients with a diagnosis of MPS IH (Hurler syndrome) are candidates for this protocol if they are being considered for hematopoietic stem cell transplantation according the University of Minnesota guidelines.

Exclusion Criteria:

Patients are less than 8 months old, or older than 3 years of age.
There is a history of clinically-severe hypersensitivity to Laronidase.
There is a contraindication for repeated lumbar puncture.
The family is not willing to undergo the necessary procedures and evaluations inherent in the study.
Consent has not been signed for participation in the 2004-09 study of intravenous Laronidase administration.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00638547

Contacts


Contact: Paul Orchard, MD	612-626-1926	orcha001@umn.edu

Contact: Teresa Kvisto, RN	612-273-2800	tkvist1@fairview.org

Locations


United States, Minnesota
	University of MInnesota, Fairview	Recruiting
	Minneapolis, Minnesota, United States, 55455
	Contact: Tim Krepski, RN 612-273-2800
	Contact: Teresa Kvisto, RN 612-273-2800 tkvist!@fairview.org

Sponsors and Collaborators

University of Minnesota

Genzyme

Investigators


Principal Investigator:	Paul Orchard, MD	University of Minnesota Medical Center

More Information

Responsible Party:	University of Minnesota ( Paul Orchard, M.D. )
Study ID Numbers:	0707M11762, MT2007-10
First Received:	March 11, 2008
Last Updated:	March 18, 2008
ClinicalTrials.gov Identifier:	NCT00638547
Health Authority:	United States: Food and Drug Administration

Study placed in the following topic categories:

Alpha-L-iduronidase deficiency

Metabolism, Inborn Errors

Mucopolysaccharidoses

Metabolic Diseases

Genetic Diseases, Inborn

Lysosomal Storage Diseases

Connective Tissue Diseases

Mucopolysaccharidosis

Metabolic disorder

Hurler syndrome

Mucopolysaccharidosis I

Additional relevant MeSH terms:

Pathologic Processes

Disease

Syndrome

Mucinoses

Carbohydrate Metabolism, Inborn Errors

ClinicalTrials.gov processed this record on August 29, 2008

Sponsors and Collaborators:	University of Minnesota Genzyme
Information provided by:	University of Minnesota
ClinicalTrials.gov Identifier:	NCT00638547