Hereditary Spastic ParaparesisPhase 2TreatSPG11NCT04768166
Testing Miglustat Administration in Subjects With Spastic Paraplegia 11
A Phase 2 study testing Miglustat 100 MG in people with Hereditary Spastic Paraparesis, run by IRCCS Fondazione Stella Maris at 1 site in Italy.
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… Read more about this study
- Who is it for?
- Ages 14 years and older
- Conditions the study is for
- Hereditary Spastic Paraparesis
- What is being tested?
- Miglustat 100 MG
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteItaly
- Study dates
- 15 Jun 2021to 15 Sep 2021
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 14 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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);
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- 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).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase 2 Pharmacological Trial to Evaluate the Safety of Miglustat Administration in Subjects With Spastic Paraplegia 11 (TreatSPG11)
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.
Read the detailed description
We will analyze the safety of Miglustat
- Conditions
- Hereditary Spastic Paraparesis
- Being tested
- Miglustat 100 MG
- Keywords
- Autophagic Lysosome Reformation, SPG11, Miglustat, Lisosomal Storage Disorders
- Medical subject headings
- Spastic Paraplegia, Hereditary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Miglustat 100 MGDrug
Also called Genorph
100mg/TID in 4w then 200mg/TID in 8 w
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: Miglustat 100 MG |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: At baseline, 24 weeks
Secondary outcomes (2)
Changes from baseline GM2/GM3 levels at 24 weeks
lipid assessments
Measured: At baseline, 24 weeks
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
Measured: At baseline, 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Feb 2021
- Study start15 Jun 2021
- Primary completion30 Aug 2021
- Study completion15 Sep 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Hereditary Spastic ParaparesisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- IRCCS Fondazione Stella Maris
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Filippo Maria Santorelli, IRCCS Fondazione Stella Maris
- Investigators
- Filippo M Santorelli, MD PhD, Principal investigator, IRCCS Stella Maris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04768166
- Sponsor's protocol ID
- TreatSPG11
- Other IDs
- 2019-002827-14, 2019
- Acronym
- TreatSPG11
- Status last verified
- Apr 2022
- First submitted
- 12 Feb 2021
- Last updated
- 11 Apr 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 30723448Boutry 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.
PubMed 29949766Branchu 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.
PubMed 28237315Lo 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.
PubMed 24954637Platt 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.
PubMed 12803928
Study at a glance
From the registry record, last updated by the sponsor on 11 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 2 Pharmacological Trial to Evaluate the Safety of Miglustat Administration in Subjects With Spastic Paraplegia 11 (TreatSPG11)
- ClinicalTrials.gov ID
- NCT04768166
- Acronym / sponsor ID
- TreatSPG11 / TreatSPG11
- Conditions
- Hereditary Spastic Paraparesis
- Keywords
- Autophagic Lysosome Reformation, SPG11, Miglustat, Lisosomal Storage Disorders
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- IRCCS Fondazione Stella MarisUniversity, hospital or other
- Study start
- 15 Jun 2021 (actual)
- Primary completion
- 30 Aug 2021 (actual)
- Study completion
- 15 Sep 2021 (actual)
- First posted
- 24 Feb 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Evaluate the safety of Miglustat administration in subjects with Spastic Paraplegia 11 | Experimental | Drug: Miglustat 100 MG100 mg of Miglustat, 3 caps per day for first 4 weeks; 100 mg of Miglustat, 6 caps per day for 8 weeks |
Who may qualify
- Ages
- 14 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- 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).
Key exclusion criteria (10 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Miglustat 100 MGAlso: Genorph100mg/TID in 4w then 200mg/TID in 8 w | Drug | Evaluate the safety of Miglustat administration in subjects with Spastic Paraplegia 11 |
Primary outcome
1-Changes from baseline blood tests at 24 weeks 2-Changes from baseline neurophysiological tests at 24 weeks 3-Report of severe adverse events
Time frame: At baseline, 24 weeks
routine blood test
2 secondary outcomes
Changes from baseline GM2/GM3 levels at 24 weeks
Time frame: At baseline, 24 weeks
Assess changes in the scores of the Spastic Paraplegia Rating Scale (SPRS) at 24 weeks
Time frame: At baseline, 24 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Apr 2022.
- Background: PubMed 30723448Bellofatto 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.
- Background: PubMed 29949766Boutry 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.
- Background: PubMed 28237315Branchu 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.
- Background: PubMed 24954637Lo 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.
- Background: PubMed 12803928Platt 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Filippo M Santorelli, MD PhD principal investigator
IRCCS Stella Maris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Miglustat 100 MG in people with Hereditary Spastic Paraparesis, run by IRCCS Fondazione Stella Maris at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
1-Changes from baseline blood tests at 24 weeks 2-Changes from baseline neurophysiological tests at 24 weeks 3-Report of severe adverse events (time frame: At baseline, 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04768166, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Apr 2022.