Testing Miglustat Administration in Subjects With Spastic Paraplegia 11

Study Overview
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Brief Summary
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Hereditary spastic paraparesis type 11 (SPG11) is caused by mutations in the SPG11 gene that produces spatacsin, a protein involved in lysosomal function. Studies performed in skin cells (fibroblasts) from SPG11 patients, mice and zebrafish models of the disease showed that the material accumulated in the lysosomes is made of glycosphingolipids (GSL). Miglustat is a drug that inhibits an enzyme called glucosylceramide synthetase (GCS) which is used for the production of GSL. Miglustat, therefore, helps to delay the production of GSL. This study aims to collect preliminary data on the safety of miglustat on the SPG11 disease and to assess biomarkers.

Detailed Description
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We will analyze the safety of Miglustat

Official Title
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Phase 2 Pharmacological Trial to Evaluate the Safety of Miglustat Administration in Subjects With Spastic Paraplegia 11 (TreatSPG11)

Conditions
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Hereditary Spastic Paraparesis

Intervention / Treatment
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* Drug: Miglustat 100 MG


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written signed informed consent; Confirmed diagnosis of SPG11; Age > 13 years; SPRS score ≥ 10 or ≤35; Use of effective contraceptive methods and the performance of pregnancy tests (only fertile subjects). Exclusion Criteria: Diagnosis of other concomitant neurodegenerative diseases; Outcomes of severe pre- or peri-natal suffering; Age ≤ 13 years; SPRS score ≥ 35 or ≤10; Hypersensitivity or intolerance to miglustat; Participation in other pharmacological studies within 30 days of the first Study visit (T0); The inability to take the drug; Any additional medical conditions; Subjects with severe renal impairment; Refusal to use effective contraceptive methods and the performance of pregnancy tests (only fertile subjects).

Ages Eligible for Study
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Minimum Age: 14 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Evaluate the safety of Miglustat administration in subjects with Spastic Paraplegia 11<br>100 mg of Miglustat, 3 caps per day for first 4 weeks; 100 mg of Miglustat, 6 caps per day for 8 weeks | Drug: Miglustat 100 MG<br>* 100mg/TID in 4w then 200mg/TID in 8 w<br>* Other names: Genorph;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1-Changes from baseline blood tests at 24 weeks 2-Changes from baseline neurophysiological tests at 24 weeks 3-Report of severe adverse events | routine blood test | At baseline, 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes from baseline GM2/GM3 levels at 24 weeks | lipid assessments | At baseline, 24 weeks | 
| Assess changes in the scores of the Spastic Paraplegia Rating Scale (SPRS) at 24 weeks | SPRS rates disease severity (0-52) with lower numbers indicating less impairement | At baseline, 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Autophagic Lysosome Reformation, Miglustat, Lisosomal Storage Disorders, SPG11