Testing Miglustat Administration in Subjects With Spastic Paraplegia 11

NCT04768166 | Completed Phase 2 DMC

• 2 other identifiers: TreatSPG112019-002827-14
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Hereditary Spastic Paraparesis

Keywords

Autophagic Lysosome Reformation; SPG11; Miglustat; Lisosomal Storage Disorders

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Changes from baseline GM2/GM3 levels at 24 weeks

  At baseline, 24 weeks

• Assess changes in the scores of the Spastic Paraplegia Rating Scale (SPRS) at 24 weeks

  At baseline, 24 weeks

Study Arms (1)

Evaluate the safety of Miglustat administration in subjects with Spastic Paraplegia 11

EXPERIMENTAL

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

Interventions

Miglustat 100 MG DRUG

100mg/TID in 4w then 200mg/TID in 8 w

Also known as: Genorph

Evaluate the safety of Miglustat administration in subjects with Spastic Paraplegia 11

Eligibility Criteria

• Age: 14 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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).

Sponsors & Collaborators

• IRCCS Fondazione Stella Maris: lead

Study Sites (1)

IRCCS Fondazione Stella Maris

Pisa, PI, 56128, Italy

Location

Related 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.

  PMID: 30723448 BACKGROUND

• 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.

  PMID: 29949766 BACKGROUND

• 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.

  PMID: 28237315 BACKGROUND

• 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.

  PMID: 24954637 BACKGROUND

• 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. doi: 10.1098/rstb.2003.1279.

  PMID: 12803928 BACKGROUND

MeSH Terms

Conditions

Spastic Paraplegia, Hereditary

Interventions

miglustat

Condition Hierarchy (Ancestors)

Hereditary Sensory and Motor Neuropathy; Nervous System Malformations; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Polyneuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn

Study Officials

• Filippo M Santorelli, MD PhD

  IRCCS Stella Maris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director Molecular Medicine, Neurogenetics and Neuromuscular Disorders

Study Record Dates

• First Submitted: February 12, 2021
• First Posted: February 24, 2021
• Study Start: June 15, 2021
• Primary Completion: August 30, 2021
• Study Completion: September 15, 2021
• Last Updated: April 11, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)