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Testing Miglustat Administration in Subjects With Spastic Paraplegia 11 (TreatSPG11)

Primary Purpose

Hereditary Spastic Paraparesis

Status
Completed
Phase
Phase 2
Locations
Italy
Study Type
Interventional
Intervention
Miglustat 100 MG
Sponsored by
IRCCS Fondazione Stella Maris
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Hereditary Spastic Paraparesis focused on measuring Autophagic Lysosome Reformation, SPG11, Miglustat, Lisosomal Storage Disorders

Eligibility Criteria

14 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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).

Sites / Locations

  • IRCCS Fondazione Stella Maris

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

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

Arm Description

100 mg of Miglustat, 3 caps per day for first 4 weeks; 100 mg of Miglustat, 6 caps per day for 8 weeks

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Changes from baseline GM2/GM3 levels at 24 weeks
lipid assessments
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

Full Information

First Posted
February 12, 2021
Last Updated
April 1, 2022
Sponsor
IRCCS Fondazione Stella Maris
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1. Study Identification

Unique Protocol Identification Number
NCT04768166
Brief Title
Testing Miglustat Administration in Subjects With Spastic Paraplegia 11
Acronym
TreatSPG11
Official Title
Phase 2 Pharmacological Trial to Evaluate the Safety of Miglustat Administration in Subjects With Spastic Paraplegia 11 (TreatSPG11)
Study Type
Interventional

2. Study Status

Record Verification Date
April 2022
Overall Recruitment Status
Completed
Study Start Date
June 15, 2021 (Actual)
Primary Completion Date
August 30, 2021 (Actual)
Study Completion Date
September 15, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
IRCCS Fondazione Stella Maris

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.
Detailed Description
We will analyze the safety of Miglustat

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hereditary Spastic Paraparesis
Keywords
Autophagic Lysosome Reformation, SPG11, Miglustat, Lisosomal Storage Disorders

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Evaluate the safety of Miglustat administration in subjects with Spastic Paraplegia 11
Arm Type
Experimental
Arm Description
100 mg of Miglustat, 3 caps per day for first 4 weeks; 100 mg of Miglustat, 6 caps per day for 8 weeks
Intervention Type
Drug
Intervention Name(s)
Miglustat 100 MG
Other Intervention Name(s)
Genorph
Intervention Description
100mg/TID in 4w then 200mg/TID in 8 w
Primary Outcome Measure Information:
Title
1-Changes from baseline blood tests at 24 weeks 2-Changes from baseline neurophysiological tests at 24 weeks 3-Report of severe adverse events
Description
routine blood test
Time Frame
At baseline, 24 weeks
Secondary Outcome Measure Information:
Title
Changes from baseline GM2/GM3 levels at 24 weeks
Description
lipid assessments
Time Frame
At baseline, 24 weeks
Title
Assess changes in the scores of the Spastic Paraplegia Rating Scale (SPRS) at 24 weeks
Description
SPRS rates disease severity (0-52) with lower numbers indicating less impairement
Time Frame
At baseline, 24 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
14 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Filippo M Santorelli, MD PhD
Organizational Affiliation
IRCCS Stella Maris
Official's Role
Principal Investigator
Facility Information:
Facility Name
IRCCS Fondazione Stella Maris
City
Pisa
State/Province
PI
ZIP/Postal Code
56128
Country
Italy

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
30723448
Citation
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.
Results Reference
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PubMed Identifier
29949766
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.
Results Reference
background
PubMed Identifier
28237315
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.
Results Reference
background
PubMed Identifier
24954637
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.
Results Reference
background
PubMed Identifier
12803928
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. doi: 10.1098/rstb.2003.1279.
Results Reference
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Testing Miglustat Administration in Subjects With Spastic Paraplegia 11

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