Contact information
Type
Scientific
Primary contact
Dr Pilar Giraldo Castellano
ORCID ID
Contact details
Servicio de Hematología
Hospital Universitario Miguel Servet
Paseo Isabel La Católica 1-3
Zaragoza
50009
Spain
+34 670285339
giraldo.p@gmail.com
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
EC-90737
Study information
Scientific title
Rational use of substrate reduction therapy and enzyme replacement therapy in patients with type I Gaucher disease: an open-label single-centre follow up study
Acronym
Study hypothesis
The aim of this study is to evaluate the long-term effect of miglustat (substrate reduction therapy) as first-line treatment in mild to moderate Gaucher Disease (GD) and its effectiveness as maintenance therapy either in patients with type I GD who have achieved a stable condition with enzyme replacement therapy or in patients with severe disease who have not reached the objectives of the treatment.
Substrate Reduction Therapy (SRT) is an effective alternative to Enzyme Replacement Therapy (ERT) in type I GD. It is administered orally, therefore it is more comfortable, has lower direct and indirect administration costs. The SRT would have indication and efficacy in patients who have reached treatment goals, for who maintaining response is necessary and in patients with advanced disease who have not reached treatment goals.
Ethics approval
Clinical Research Ethics Committee of Aragon (Comité Ético de Investigación Clínica de Aragón (CEICA).
Ref: C.I. EC07/083, 20/05/2008
Study design
Open-label single centre follow-up study
Primary study design
Interventional
Secondary study design
Non randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Type I Gauchers disease
Intervention
Asymptomatic patients with a severity scale of 0-3 points are not treated but monitored and assessed every 6 months (clinically, laboratory and imaging). New diagnosed symptomatic patients with a severity scale of 0-3 points would be eligible for SRT (100 mg/TID PO) or ERT (30 U/kg IV every 2 weeks) in function of individual characteristics and preferences. New diagnosed symptomatic patients with a severity scale of 4-8 points would be eligible for SRT (100 mg/TID PO) or ERT (60 U/kg IV every 2 weeks) in function of individual characteristics and preferences. New diagnosed symptomatic patients with a severity scale >9 points will receive ERT (60 U/kg IV every 2 weeks). Patients previously treated with ERT and have reached stability for a minimum of 2 years will receive treatment with SRT (100 mg/TID PO). For all treatment arms, the patients will be followed during 24 months. Test that will be run: Magnetic resonance imaging (MRI) spleen and liver volume measurement (basal and every 6 months), MRI femoral and lumbar spinal bone marrow infiltration (basal and months 12 and 24), biomarkers of GD activity such as chitotriosidase, angiotensin-converting enzyme (ACE), tartrate-resistant acid phosphatase (TRAP) and ferritin, and including platelets, hemoglobin and vit B12 (all visits), QLQ SF-36 (basal and months 12 and 24), global improvement scale (patient / investigator, all visits from visit 2), Visual Analog Scale for pain assessment (all visits), neurologic and neuropsychological tests including electroneurography (basal and every 6 months), physical examination and vital signs (basal and months 12 and 24)
Intervention type
Drug
Phase
Not Applicable
Drug names
Miglustat
Primary outcome measures
The primary end point is the percentage change in liver volume in baseline visit and every six months upto 24 months measured by MRI
Secondary outcome measures
1. The percentage change in spleen volume every six months and bone marrow infiltration measured yearly [baseline visit (visit 1), 12 months (visit 4) and 24 months (visit 6)] by MRI 2. Changes in hAematologic parameters (haemoglobin, platelets)
3. Chitotriosidase activity measured every two years (in baseline visit and visit 6)
Overall trial start date
01/12/2009
Overall trial end date
31/12/2011
Reason abandoned
Eligibility
Participant inclusion criteria
1. Patients ≥ 18 years. Diagnosis of type I GD confirmed by glucocerebrosidase assay or by the presence of mutations in the glucocerebrosidase gene
2. Patients who have received enzyme replacement therapy for at least 3 years with the same dose for at least the last 6 months
3. Stable clinical and biological disease for 2 years confirmed with at least two assessments including the one performed at baseline
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
40
Participant exclusion criteria
1. History of oculomotor palsy, ataxia or other manifestations usually associated with type 3 GD
2. Splenectomy before 18 years due to massive splenomegaly or severe cytopenia
3. Documented peripheral polyneuropathy. Intolerance to lactose
4. Diarrhoea of unknown origin within 6 months prior to visit 1 or history of significant gastrointestinal disorders
5. Cataracts or a known risk of cataract formation
6. Severe renal insufficiency
7. Active intercurrent diseases, such as human immunodeficiency virus (HIV) or hepatitis B or C
8. Dependence or current abuse of drugs or alcohol
9. Suspected hypersensitivity to miglustat or any of the excipients
10. Patients who have previously received miglustat
11. Pregnancy or breast-feeding
12. Patients who refuse to use a reliable contraceptive method throughout the study and during the three months following the discontinuation of miglustat
13. Patients receiving treatment with another investigational product or have received an investigational product in the 3 months prior to baseline
Recruitment start date
01/12/2009
Recruitment end date
31/12/2011
Locations
Countries of recruitment
Spain
Trial participating centre
Servicio de Hematología
Zaragoza
50009
Spain
Sponsor information
Organisation
Aragon Institute of Health Sciences [Instituto Aragonés de Ciencias de la Salud] (Spain)
Sponsor details
c/o Esteban de Manuel Kenoy
Avenida Gómez Laguna 25
Planta 3
Zaragoza
50009
Spain
emlopezh.iacs@aragon.es
Sponsor type
Government
Website
Funders
Funder type
Government
Funder name
Aragon Institute of Health Sciences [Instituto Aragonés de Ciencias de la Salud] (Spain)
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