Clinical trial NCT04912609: Trehalose Administration in Subjects With Spastic Paraplegia 11 (3AL-SPG11)
Official title: An Observational Study in Subjects With Spastic Paraplegia Type 11 Taking Trehalose
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Hereditary Spastic Paraplegia
Spastic Paraplegia Type 11
Lead sponsor: IRCCS Fondazione Stella Maris
Sponsor class: OTHER
First posted: 2021-06-03
Enrollment: 13
Sex: ALL
Minimum age (years): 10
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
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.

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Changes from baseline in Spastic Paraplegia Rating Scale (SPRS) at 6 and 12 months
timeFrame: At baseline, month 6, month 12
Secondary outcomes:
measure: Changes in glycosphingolipids and gangliosides plasmatic levels
timeFrame: At baseline, month 6, month 12
Other outcomes:
Locations:
city: Pisa
country: Italy
facility: IRCCS Fondazione Stella Maris
state: PI
Study officials:
affiliation: Filippo Santorelli-Lab Med Molecolare
name: Filippo M Santorelli, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
citation: 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.
citation: 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.
citation: 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. doi: 10.1093/hmg/ddi422. Epub 2005 Nov 25.