Trehalose Administration in Subjects With Spastic Paraplegia 11 (3AL-SPG11) (3AL-SPG11)

An Observational Study in Subjects With Spastic Paraplegia Type 11 Taking Trehalose

Hereditary spastic paraparesis type 11 (SPG11) is caused by mutations in the SPG11 gene that produces spatacsin, a protein involved in lysosomal function.

Study Overview

• Status: Completed
• Conditions: Hereditary Spastic Paraplegia; Spastic Paraplegia Type 11

Detailed Description

Several experiments on subjects affected by neurodegenerative diseases with dysfunction of the autophagic-lysosomal system show that trehalose improves the pathological phenotype. This evidence indicates that trehalose could be used in patients with SPG11 to try to prevent the accumulation of glycosphingolipids at the lysosomal level and induce the genesis of new lysosomes. This study aims to record clinical data of 20 patients with SPG11 who take trehalose during 12 months.

• Study Type: Observational
• Enrollment (Actual): 13

Contacts and Locations

Study Locations

• Italy
  • PI
    • Pisa, PI, Italy, 56128
      • IRCCS Fondazione Stella Maris

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Subjects will be enrolled in our centre (IRCCS Fondazione Stella Maris) as part of the primary care during regular visits.

Description

Inclusion Criteria:

• Confirmed diagnosis of SPG11
• Written signed informed consent

Exclusion Criteria:

• Diagnosis of other concomitant neurodegenerative diseases
• taking other experimental drugs within 30 days of the first Study visit (T0) and during the study
• Refusal to sign informed consent

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes from baseline in Spastic Paraplegia Rating Scale (SPRS) at 6 and 12 months	Assess changes in score of the Spastic Paraplegia Rating Scale (SPRS) over ± 10%	At baseline, month 6, month 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in glycosphingolipids and gangliosides plasmatic levels	Assess changes in glycosphingolipids and gangliosides plasmatic levels over ± 10%	At baseline, month 6, month 12

Collaborators and Investigators

• Sponsor: IRCCS Fondazione Stella Maris
• Investigators: Principal Investigator: Filippo M Santorelli, MD PhD, Filippo Santorelli-Lab Med Molecolare

Publications and helpful links

General Publications

• 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.
• 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.
• Chang J, Lee S, Blackstone C. Spastic paraplegia proteins spastizin and spatacsin mediate autophagic lysosome reformation. J Clin Invest. 2014 Dec;124(12):5249-62. doi: 10.1172/JCI77598. Epub 2014 Nov 3.
• de Souza PVS, de Rezende Pinto WBV, de Rezende Batistella GN, Bortholin T, Oliveira ASB. Hereditary Spastic Paraplegia: Clinical and Genetic Hallmarks. Cerebellum. 2017 Apr;16(2):525-551. doi: 10.1007/s12311-016-0803-z. Review.
• Davies JE, Sarkar S, Rubinsztein DC. Trehalose reduces aggregate formation and delays pathology in a transgenic mouse model of oculopharyngeal muscular dystrophy. Hum Mol Genet. 2006 Jan 1;15(1):23-31. Epub 2005 Nov 25.

Study record dates

Study Major Dates

• Study Start (Actual): June 30, 2021
• Primary Completion (Actual): April 30, 2022
• Study Completion (Actual): July 30, 2022

Study Registration Dates

• First Submitted: May 28, 2021
• First Submitted That Met QC Criteria: June 2, 2021
• First Posted (Actual): June 3, 2021

Study Record Updates

• Last Update Posted (Actual): August 3, 2022
• Last Update Submitted That Met QC Criteria: August 2, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Congenital Abnormalities; Genetic Diseases, Inborn; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Peripheral Nervous System Diseases; Neuromuscular Manifestations; Heredodegenerative Disorders, Nervous System; Nervous System Malformations; Paralysis; Muscle Hypertonia; Polyneuropathies; Hereditary Sensory and Motor Neuropathy; Muscle Spasticity; Paraplegia; Spastic Paraplegia, Hereditary
• Other Study ID Numbers: 3AL-SPG11

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No