Testing Miglustat Administration in Subjects With Spastic Paraplegia 11

Hereditary Spastic Paraparesis Clinical Trial

— TreatSPG11  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04768166
• Other study ID #: TreatSPG11
• Secondary ID: 2019-002827-14
• Status: Completed
• Phase: Phase 2
• Start date: June 15, 2021
• Est. completion date: September 15, 2021

Study information

• Verified date: April 2022
• Source: IRCCS Fondazione Stella Maris
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

We will analyze the safety of Miglustat

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: September 15, 2021
• Est. primary completion date: August 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 14 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Hereditary Spastic Paraparesis
• Muscle Spasticity
• Paraparesis
• Paraparesis, Spastic
• Paraplegia

Intervention

Drug:
• Miglustat 100 MG
100mg/TID in 4w then 200mg/TID in 8 w

Locations

Country	Name	City	State
Italy	IRCCS Fondazione Stella Maris	Pisa	PI

Sponsors (1)

Lead Sponsor	Collaborator
IRCCS Fondazione Stella Maris

Country where clinical trial is conducted

Italy, 

References & Publications (5)

Bellofatto M, De Michele G, Iovino A, Filla A, Santorelli FM. Management of Hereditary Spastic Paraplegia: A Systematic Review of the Literature. Front Neurol. 2019 Jan 22;10:3. doi: 10.3389/fneur.2019.00003. eCollection 2019. — View Citation

Boutry M, Branchu J, Lustremant C, Pujol C, Pernelle J, Matusiak R, Seyer A, Poirel M, Chu-Van E, Pierga A, Dobrenis K, Puech JP, Caillaud C, Durr A, Brice A, Colsch B, Mochel F, El Hachimi KH, Stevanin G, Darios F. Inhibition of Lysosome Membrane Recycling Causes Accumulation of Gangliosides that Contribute to Neurodegeneration. Cell Rep. 2018 Jun 26;23(13):3813-3826. doi: 10.1016/j.celrep.2018.05.098. — View Citation

Branchu J, Boutry M, Sourd L, Depp M, Leone C, Corriger A, Vallucci M, Esteves T, Matusiak R, Dumont M, Muriel MP, Santorelli FM, Brice A, El Hachimi KH, Stevanin G, Darios F. Loss of spatacsin function alters lysosomal lipid clearance leading to upper and lower motor neuron degeneration. Neurobiol Dis. 2017 Jun;102:21-37. doi: 10.1016/j.nbd.2017.02.007. Epub 2017 Feb 22. — View Citation

Lo Giudice T, Lombardi F, Santorelli FM, Kawarai T, Orlacchio A. Hereditary spastic paraplegia: clinical-genetic characteristics and evolving molecular mechanisms. Exp Neurol. 2014 Nov;261:518-39. doi: 10.1016/j.expneurol.2014.06.011. Epub 2014 Jun 20. Review. — View Citation

Platt FM, Jeyakumar M, Andersson U, Heare T, Dwek RA, Butters TD. Substrate reduction therapy in mouse models of the glycosphingolipidoses. Philos Trans R Soc Lond B Biol Sci. 2003 May 29;358(1433):947-54. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Changes from baseline GM2/GM3 levels at 24 weeks	lipid assessments	At baseline, 24 weeks
Secondary	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