Condition category
Nutritional, Metabolic, Endocrine
Date applied
06/03/2007
Date assigned
06/03/2007
Last edited
06/03/2007
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Dr A A M Zandbergen

ORCID ID

Contact details

Erasmus Medical Centre Rotterdam
Department of Internal Medicine
P.O. Box 2040
Rotterdam
3000 CA
Netherlands
a.zandbergen@erasmusmc.nl

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

N/A

Study information

Scientific title

Acronym

Study hypothesis

Mucopolysaccharidosis type I (MPS I) is caused by the deficiency of the lysosomal enzyme a-L-Iduronidase. Due to this deficiency heparan sulphate and dermatan sulphate (Glycosaminoglycans [GAGs]) accumulate in the lysosomes of all cells, but predominantly in the connective tissue. Clinical features encompass a spectrum of disease manifestations. Three phenotypes are recognised:
1. The neuronopathic (Hurler) type at one end of the spectrum
2. An intermediate (Hurler-Scheie) phenotype
3. A non-neuronopathic (Scheie) phenotype at the far end of the spectrum

In both the non-neuronopathic and neuronopathic forms, visceral complications occur, such as joint abnormalities, hepatomegaly, cardiac valve abnormalities, skeletal abnormalities and corneal clouding. The most severe expression of the disease is found in the neuronopathic form; here visceral symptoms occur very early in life, with concomitant devastating, irreversible central nervous system involvement, giving rise to considerable morbidity from a very early age onwards and death on average around the fifth year of age.

In the Scheie phenotype psychomotor development is normal. Skeletal and joint manifestations form the important disease burden in these patients. Recently, trials with weekly a-L-Iduronidase (Aldurazyme™, Genzyme/Biomarin) infusions showed improvement in joint mobility, lung function and exercise tolerance, as determined by the six minute walk test. Aldurazyme™ received marketing approval as an orphan drug from the European Medicines Agency (EMEA) in April 2003. However, there are still many open issues regarding the efficacy of treatment, making uniform evaluation of treatment in selected groups of MPS I patients mandatory.

Hypothesis:
MPS I patients can be treated with Aldurazyme safely and effectively.

Ethics approval

Ethics approval received from the local medical ethics committee

Study design

Non-randomised, non-controlled, parallel group, multicentre clinical trial

Primary study design

Interventional

Secondary study design

Multi-centre

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Condition

Mucopolysaccharidosis type I

Intervention

Enzyme replacement therapy with Aldurazyme™.

Intervention type

Drug

Phase

Not Specified

Drug names

Recombinant human a-L-iduronidase (Aldurazyme™)

Primary outcome measures

1. Improvement of joint mobility
2. Improvement of quality of life

Secondary outcome measures

1. Improvement of sleep apnea registration
2. Improvement in six-minute walk test
3. Improvement of cardiac geometry and function
4. Improvement in lung function
5. Improved motor performance (handicap status)
6. Evaluation of visual acuity/performance
7. Evaluation of mental condition and social performance
8. Decrease of liver and/or spleen size as measured by ultrasound
9. Effect of dose and infusion rate on plasma enzyme levels and enzyme availability

Overall trial start date

01/01/2004

Overall trial end date

31/12/2005

Reason abandoned

Eligibility

Participant inclusion criteria

1. The patient must give written informed consent
2. If the patient is younger than 12 years, informed consent from his/her parents or his/her legal representative is necessary
3. If the patient is below 18 years, but older than 12 years, informed consent from the child is necessary if the patient is mentally and physically able to do so
4. The patients can be included in this protocol, and not in any of the two other MPS I treatment protocols
5. The patient must have a current diagnosis of MPS I, as documented by a decreased a-L-iduronidase activity in leukocytes or fibroblasts
6. Patients must be willing and able to comply with the study protocol
7. Female patients must have a negative pregnancy test, and must use a medically accepted method of contraception during the study

Participant type

Patient

Age group

Child

Gender

Both

Target number of participants

35

Participant exclusion criteria

1. Patient is unable or unwilling to comply with the study protocol
2. Parent(s) or legal representatives are unable or unwilling to comply with the evaluation program
3. Patient is pregnant or lactating
4. Life expectancy less than six months
5. Very severe neurological involvement as evidenced by:
a. total or subtotal absence of cortical activity (vegetative state)
b. untreatable seizures
c. loss of (almost) all abilities to communicate

Recruitment start date

01/01/2004

Recruitment end date

31/12/2005

Locations

Countries of recruitment

Netherlands

Trial participating centre

Erasmus Medical Centre Rotterdam
Rotterdam
3000 CA
Netherlands

Sponsor information

Organisation

Erasmus Medical Centre (The Netherlands)

Sponsor details

Sophia Children's Hospital
Department of Metabolic Diseases
P.O. Box 2040
Rotterdam
3015 GJ
Netherlands

Sponsor type

Hospital/treatment centre

Website

http://www.erasmusmc.nl/

Funders

Funder type

Government

Funder name

Dutch Health Care Insurance Board (College Voor Zorgverzekeringen [CVZ]) (The Netherlands)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes