Clinical Trial: A Study of Intrathecal Enzyme Therapy for Cognitive Decline in MPS I
Study Status: Completed
Recruit Status: Completed
Study Type: Interventional
Official Title: A Study of Intrathecal Enzyme Replacement for Cognitive Decline in Mucopolysaccharidosis I
Brief Summary:
This is a 24-month study of the use of laronidase administered into the spinal fluid to treat cognitive decline in mucopolysaccharidosis I (MPS I). MPS I is a rare genetic condition due to deficiency of the enzyme alpha-l-iduronidase. Laronidase is the manufactured form of the enzyme alpha-l-iduronidase.
MPS I is a heterogeneous disease with several clinical phenotypes ranging from the most severe, Hurler syndrome, to the attenuated forms, Hurler-Scheie and Scheie. Although patients with milder forms of MPS I may not have grossly observable problems with cognition, these patients do have learning difficulties that are apparent in school and with neuropsychological testing. The goal of this study is to evaluate whether intrathecal recombinant human alpha-l-iduronidase (rhIDU) injections can stabilize or improve cognitive decline in individuals with MPS I.
Detailed Summary:
This study is a 24-month open label, prospective, randomized trial in 16 MPS I patients age six years or older who have documented evidence of cognitive decline. The study will test the safety and efficacy of intrathecal recombinant human alpha-L iduronidase (rhIDU) to reduce or stabilize cognitive decline by assessing the subjects at baseline with neuropsychological, clinical, radiological, and biochemical evaluations and then monitoring the change in these parameters during a regimen of first monthly, then quarterly, intrathecal treatments with rhIDU. The clinical safety of the regimen will be assessed by monitoring of adverse events, cerebrospinal fluid (CSF) laboratory assessments, and clinical evaluations.
Subjects will be randomized to a treatment or a control group for 12 months, following which all subjects will receive 12 months of active treatment. During the first 12 months, the control group will receive similar study assessments but will be unblinded with no placebo administered. Subjects will have extensive baseline screening evaluations, after which subjects who were randomized to the treatment group will receive their first dose of intrathecal rhIDU. The enzyme will be administered via intrathecal injection at 1-3 month intervals throughout the 24-month study period. There will be a mid-study analysis after 12 months comparing changes in IQ and memory tests between controls and the treatment group. If pre-established criteria of improvement are met, the study will terminate at the 12 month point. If shown to be effective, intrathecal enzyme replacement therapy (ERT) would be the only treatment for cognitive decline in patients who do not qualify for and/or are unable to have hematopoietic stem cell transplantation.
Sponsor: Patricia I. Dickson, M.D.
Current Primary Outcome: The objective of this study is to assess the ability of intrathecal α-L-iduronidase to be administered safely [ Time Frame: 24 months ]
Original Primary Outcome: Same as current
Current Secondary Outcome: The objective of this study is to assess the ability of intrathecal α-L-iduronidase to stabilize or reverse cognitive decline. [ Time Frame: 24 months ]
Original Secondary Outcome: Same as current
Information By: Dickson, Patricia I., M.D.
Dates:
Date Received: February 25, 2009
Date Started: June 2009
Date Completion:
Last Updated: January 22, 2016
Last Verified: January 2016
