Cognitive DeclineNCT00852358
A Study of Intrathecal Enzyme Therapy for Cognitive Decline in MPS I
A study testing laronidase in people with Cognitive Decline and Mucopolysaccharidosis I, run by Patricia I. Dickson, M.D. at 3 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 6 years and older
- Conditions the study is for
- Cognitive Decline, Mucopolysaccharidosis I, Hurler-Scheie Syndrome
- What is being tested?
- laronidase
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 3 sitesUnited States
- Study dates
- Jun 2009to Apr 2015
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- The presence of MPS I disease as documented by low α-L-iduronidase activity
- Age six years or older.
- The presence of acquired cognitive deficits as demonstrated by:
- A score of one standard deviation below mean on IQ testing or in one domain of neuropsychological function (language, memory, or non-verbal ability), OR
- Documented historical evidence of a decline of greater than one standard deviation on sequential testing, OR
- A score between 0.75 and 1 standard deviation below the mean, AND the cognitive deficit affects daily performance.
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- The decline in function is not explainable by other neurological or psychiatric factors.
- Subject and/or guardian willing and able to provide written informed consent.
- Negative urine pregnancy test at screening (non-sterile females of child-bearing potential only)
- Currently using two acceptable methods of birth control as determined by the investigator and willing to continue to use acceptable birth control during their participation in the study (non-sterile females of child-bearing potential who are sexually active only)
- Willing and able to comply with study procedures. For example, the subjects must be able to complete written and computer-based testing. The subjects must be able to lie still in the MRI scanner for at least 40 minutes without sedation.
Who cannot join
- The subject has undergone hematopoietic stem cell transplantation
- Recent initiation of intravenous Aldurazyme® therapy with less than 6 months of therapy. Subjects who have been receiving Aldurazyme® therapy for more than 6 months, and those who have never received Aldurazyme® therapy, will be allowed to enroll
- Pregnant or lactating, or considering pregnancy
- Receipt of an investigational drug or procedure within 30 days of enrollment
- A condition, medical or other, that prevents participation in the study, including severe auditory or visual impairment, significant lumbar pathology, lumbar catheter, or recent major surgery within 6 weeks that would preclude their ability to participate.
- Infusion reactions to intravenous Aldurazyme® therapy that require ongoing medical intervention, special prophylaxis or altered rate or dose of enzyme administration
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- The subject has a programmable VP shunt that is incompatible with the 3 Tesla MRI magnet and is unable or unwilling to undergo shunt revision to a MRI compatible device.
- The subject has another contraindication for MRI, such as nonremovable metal in the body.
- The subject has severely impaired spinal CSF flow, demonstrated by failure of appearance of 99mTechnetium-DTPA in the basal cisterns by 4 hours after intra-lumbar administration.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
University of Minnesota
Minneapolis, Minnesota, 55455
Children's Hospital & Research Center Oakland
Oakland, California, 94609-1809
Los Angeles Biomedical Institute at Harbor-UCLA
Torrance, California, 90502
About this study
Official title: A Study of Intrathecal Enzyme Replacement for Cognitive Decline in Mucopolysaccharidosis I
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.
Read the detailed description
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.
- Conditions
- Cognitive Decline, Mucopolysaccharidosis I, Hurler-Scheie Syndrome, Scheie Syndrome, Lysosomal Storage Disease
- Being tested
- laronidase
- Keywords
- mucopolysaccharidosis, Hurler-Scheie, Scheie, laronidase, cognitive decline, central nervous system, enzyme replacement therapy, intrathecal, LA Biomed
- Medical subject headings
- Cognitive Dysfunction, Mucopolysaccharidosis I, Lysosomal Storage Diseases, Mucopolysaccharidoses
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
laronidaseDrug
Also called Aldurazyme, recombinant human alpha-l-iduronidase
For the treatment group, intrathecal rhIDU injections will consist of 3 cc of Aldurazyme® (laronidase) (approximately 1.74 mg) diluted with 6 cc of Elliotts B® solution for a total injection of 9 cc. The diluted enzyme will be administered via a lumbar puncture (IT) on day 0 after baseline assessments. IT injections will be repeated on days 30, 60, and 90. The subsequent doses will be administered at 3-month intervals for a total of 10 doses during the two-year period. Control patients will not receive treatment, lumbar puncture, or placebo, but will undergo all other study procedures and assessments during year one. Control patients will then enter a treatment phase consisting of four IT doses at 3-month intervals.
| Study group | Role | What they receive |
|---|---|---|
| intrathecal laronidase | Experimental | The Experimental treatment group will receive study assessments and intrathecal laronidase (1.74 mg laronidase) treatments every 1-3 months beginning at start of study. Receives: Drug: laronidase |
| Control Group | Other | During the first 11 months, the control group will receive study assessments but will be unblinded with no intrathecal treatment or placebo administered. Beginning at month 12, the control group will receive intrathecal laronidase (1.74 mg) treatment every 3 months (months 12, 15, 18, and 21). Receives: Drug: laronidase |
What is being measured
The primary outcome is the main question the study is designed to answer.
The objective of this study is to assess the ability of intrathecal α-L-iduronidase to be administered safely
Measured: 24 months
Secondary outcomes (1)
The objective of this study is to assess the ability of intrathecal α-L-iduronidase to stabilize or reverse cognitive decline.
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Feb 2009 (estimated)
- Study startJun 2009
- Primary completionApr 2015
- Study completionApr 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cognitive DeclineStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Patricia I. Dickson, M.D.
- Collaborators
- The Ryan Foundation, BioMarin Pharmaceutical, Rare Diseases Clinical Research Network, National Center for Advancing Translational Sciences (NCATS), National Institute of Neurological Disorders and Stroke (NINDS), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), University of Minnesota, University of California, Los Angeles
- Responsible party
- Sponsor-investigator, Patricia I. Dickson, M.D., Dickson, Patricia I., M.D.
- Investigators
- Agnes Chen, MD, Principal investigator, Los Angeles Biomedical Institute at Harbor-UCLAPatricia I Dickson, MD, Principal investigator, Los Angeles Biomedical Institute at Harbor-UCLA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00852358
- Sponsor's protocol ID
- MIRC-002
- Other IDs
- MIRC-002, IRB Project No. 13270-01, IND 104,354, U54NS065768
- Status last verified
- Jan 2016
- First submitted
- 25 Feb 2009
- Last updated
- 26 Jan 2016
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Jan 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Study of Intrathecal Enzyme Replacement for Cognitive Decline in Mucopolysaccharidosis I
- ClinicalTrials.gov ID
- NCT00852358
- Acronym / sponsor ID
- MIRC-002
- Conditions
- Cognitive Decline, Mucopolysaccharidosis I, Hurler-Scheie Syndrome, Scheie Syndrome, Lysosomal Storage Disease
- Keywords
- mucopolysaccharidosis, Hurler-Scheie, Scheie, laronidase, cognitive decline, central nervous system, enzyme replacement therapy, intrathecal
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Patricia I. Dickson, M.D.
- Collaborators
- The Ryan Foundation, BioMarin Pharmaceutical, Rare Diseases Clinical Research Network, National Center for Advancing Translational Sciences (NCATS), National Institute of Neurological Disorders and Stroke (NINDS), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), University of Minnesota, University of California, Los Angeles
- Study start
- Jun 2009
- Primary completion
- Apr 2015 (actual)
- Study completion
- Apr 2015 (actual)
- First posted
- 27 Feb 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| intrathecal laronidase | Experimental | Drug: laronidaseThe Experimental treatment group will receive study assessments and intrathecal laronidase (1.74 mg laronidase) treatments every 1-3 months beginning at start of study. |
| Control Group | Other | Drug: laronidaseDuring the first 11 months, the control group will receive study assessments but will be unblinded with no intrathecal treatment or placebo administered. Beginning at month 12, the control group will receive intrathecal laronidase (1.74 mg) treatment every 3 months (months 12, 15, 18, and 21). |
Who may qualify
- Ages
- 6 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (11 listed)
- The presence of MPS I disease as documented by low α-L-iduronidase activity
- Age six years or older.
- The presence of acquired cognitive deficits as demonstrated by:
- The decline in function is not explainable by other neurological or psychiatric factors.
- Subject and/or guardian willing and able to provide written informed consent.
Key exclusion criteria (9 listed)
- The subject has undergone hematopoietic stem cell transplantation
- Recent initiation of intravenous Aldurazyme® therapy with less than 6 months of therapy. Subjects who have been receiving Aldurazyme® therapy for more than 6 months, and those who have never received Aldurazyme® therapy, will be allowed to enroll
- Pregnant or lactating, or considering pregnancy
- Receipt of an investigational drug or procedure within 30 days of enrollment
- A condition, medical or other, that prevents participation in the study, including severe auditory or visual impairment, significant lumbar pathology, lumbar catheter, or recent major surgery within 6 weeks that would preclude their ability to participate.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| laronidaseAlso: Aldurazyme, recombinant human alpha-l-iduronidaseFor the treatment group, intrathecal rhIDU injections will consist of 3 cc of Aldurazyme® (laronidase) (approximately 1.74 mg) diluted with 6 cc of Elliotts B® solution for a total injection of 9 cc. The diluted enzyme will be administered via a lumbar puncture (IT) on day 0 after baseline assessments. IT injections will be repeated on days 30, 60, and 90. The subsequent doses will be administered at 3-month intervals for a total of 10 doses during the two-year period. Control patients will not receive treatment, lumbar puncture, or placebo, but will undergo all other study procedures and assessments during year one. Control patients will then enter a treatment phase consisting of four IT doses at 3-month intervals. | Drug | Control Group, intrathecal laronidase |
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
1 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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jan 2016.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Agnes Chen, MD principal investigator
Los Angeles Biomedical Institute at Harbor-UCLA
Patricia I Dickson, MD principal investigator
Los Angeles Biomedical Institute at Harbor-UCLA
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing laronidase in people with Cognitive Decline and Mucopolysaccharidosis I, run by Patricia I. Dickson, M.D. at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Jan 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The objective of this study is to assess the ability of intrathecal α-L-iduronidase to be administered safely (time frame: 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jan 2016.