Rational use of substrate reduction therapy and enzyme replacement therapy in patients with type I Gaucher disease (Uso racional de los tratamientos por inhibición de sustrato y enzimático sustitutivo en pacientes con enfermedad de Gaucher tipo I)
| ISRCTN | ISRCTN05147495 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN05147495 |
| Secondary identifying numbers | EC-90737 |
- Submission date
- 31/01/2011
- Registration date
- 18/04/2011
- Last edited
- 18/04/2011
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Nutritional, Metabolic, Endocrine
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year
Plain English summary of protocol
Not provided at time of registration
Contact information
Dr Pilar Giraldo Castellano
Scientific
Scientific
Servicio de Hematología
Hospital Universitario Miguel Servet
Paseo Isabel La Católica 1-3
Zaragoza
50009
Spain
| Phone | +34 670285339 |
|---|---|
| giraldo.p@gmail.com |
Study information
| Study design | Open-label single centre follow-up study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Non randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet |
| 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 |
| Study objectives | 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(s) | Clinical Research Ethics Committee of Aragon (Comité Ético de Investigación Clínica de Aragón (CEICA). Ref: C.I. EC07/083, 20/05/2008 |
| Health condition(s) or problem(s) studied | 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 |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Miglustat |
| Primary outcome measure | 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 study start date | 01/12/2009 |
| Completion date | 31/12/2011 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 40 |
| Key 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 |
| Key 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 |
| Date of first enrolment | 01/12/2009 |
| Date of final enrolment | 31/12/2011 |
Locations
Countries of recruitment
- Spain
Study participating centre
Servicio de Hematología
Zaragoza
50009
Spain
50009
Spain
Sponsor information
Aragon Institute of Health Sciences [Instituto Aragonés de Ciencias de la Salud] (Spain)
Government
Government
c/o Esteban de Manuel Kenoy
Avenida Gómez Laguna 25
Planta 3
Zaragoza
50009
Spain
| emlopezh.iacs@aragon.es | |
| Website | http://www.aragon.es/ |
"ROR" |
https://ror.org/05p0enq35 |
Funders
Funder type
Government
Aragon Institute of Health Sciences [Instituto Aragonés de Ciencias de la Salud] (Spain)
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
