SPG7CONSP-HET7NCT05127967
Consequences of Mutations in the SPG7 Gene at the Heterozygous State
A study testing Skin biopsy in people with SPG7, run by University Hospital, Montpellier at 1 site in France.
Trial summary
Paraplegin, encoded by the SPG7 gene, is an ATP-dependent mAAA protease located in the inner mitochondrial membrane. Its function is not fully understood. Mutations in the SPG7 gene are responsible for spastic paraplegia type 7. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- SPG7
- What is being tested?
- Skin biopsy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 1 siteFrance
- Study dates
- 16 Nov 2021to 26 Jan 2022
- Phase
- Interventional
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age > or equal to 18 years
- Subject who is already undergoing neurosurgical intervention as part of the care pathway for an for an acquired, non-genetic neurological problem (e.g. herniated disc, narrow lumbar canal)
- Non-inclusion Criteria of cases
- Refusal to sign the written informed consent signed by the patient (or by his representative in case of a patient under guardianship.
- Patients with specific contraindications for skin biopsy current anticoagulant treatment; any pathologies that may cause a risk of bleeding (e.g. hemophiliacs)
- Refusal of the patient, of the guardian if necessary, to sign the informed consent to participate in the in the research
Show all 14Show fewer
- Not being a beneficiary of a social protection plan Patient deprived of liberty
- Non-inclusion Criteria of controls
- Patients with a genetic neurological disease or mitochondrial disease
- Patients with specific contraindications for skin biopsy: current anticoagulant treatment; all pathologies that may cause a risk of bleeding (e.g. hemophilia)
- Refusal to sign the informed consent to participate in the research
- Not benefiting from a social protection plan
- Patient deprived of liberty
- Patient under guardianship or curatorship
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phenotypic, Biological and Functional Consequences of Mutations in the SPG7 Gene at the Heterozygous State
Paraplegin, encoded by the SPG7 gene, is an ATP-dependent mAAA protease located in the inner mitochondrial membrane. Its function is not fully understood. Mutations in the SPG7 gene are responsible for spastic paraplegia type 7. Although spastic paraplegia type 7 is considered to be a recessive disease, some clinical observations also point to a detrimental effect of a variant in SPG7 in the heterozygous state. Thus, the presence of a single mutated variant of the SPG7 gene could be a risk factor for the development of neurological diseases. This has important implications for genetic counseling of patients and for the understanding of the function of the SPG7 protein and the mechanisms of disease development.
Read the detailed description
Although spastic paraplegia type 7 is considered to be a recessive disease, some clinical observations also argue for a detrimental effect of a variant in SPG7 in the heterozygous state. Thus, the presence of a single mutated variant of the SPG7 gene could be a risk factor for the development of neurological diseases. This has important implications for genetic counseling of patients and for the understanding of the function of the SPG7 protein and the mechanisms of disease development. To date there have been no studies to specifically explore the pathogenic role of single heterozygous variants in the SPG7 gene.
The aim of this project is to fully characterize different models expressing single heterozygous SPG7 mutations in order to detect phenotypical, biological or functional alterations. In particular, the investigators will conduct analysis on fibroblasts from symptomatic patients with mutations in the SPG7 gene (homozygous, compound heterozygous or single heterozygous), and controls. Cellular models will be particularly useful in order to study an alteration in calcium homeostasis and in the response to ER stressors. In parallel, studies will be performed using the genetic animal model of Drosophila melanogaster.
- Conditions
- SPG7
- Being tested
- Skin biopsy
- Keywords
- SPG7, Dominant, human, Drosophila, mitochondria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Skin biopsyOther
A skin biopsy involves taking a piece of skin to obtain cells (fibroblasts). Skin biopsy is a minimally invasive examination and a technically simple procedure performed with a 3mm diameter punch, or with a scalpel under local anesthesia (Lidocaine patch). The procedure can be done in a consultation office with strict asepsis. It lasts 15 minutes in total + the time to reach between putting on the lidocaine patch and performing the procedure. This biopsy will usually be done on the inside of the arm. In the majority of cases, it is not helpful to close the scar with stitches.
| Study group | Role | What they receive |
|---|---|---|
| Patients with neurological symptoms and two mutations in the SPG7 gene | Other | Symptomatic patients with SPG7 mutations (homozygous or compound heterozygous) Receives: Other: Skin biopsy |
| Patients with neurological symptoms and one mutation in the SPG7 gene | Other | Patients presenting neurological symptoms corresponding to SPG7 disease (adult onset spastic ataxia with CPEO and/or optic atrophy) with only one mutation found in the SPG7 gene Receives: Other: Skin biopsy |
| Controls | Other | Patients without mutations in the SPG7 gene requiring spinal surgery because of a non-genetic neurologic disorders Receives: Other: Skin biopsy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mitochondrial respiratory activity measured by Seahorse analyser and quantification of mADN vs nuclear AND in activity in patients with neurological symptoms and one or two mutations in the SPG7 gene vs controls
Measured: Inclusion
Mitochondrial dimension and morphology by electronic microscopy and quantification of mitochondrial motility by direct imaging activity in patients with neurological symptoms and one or two mutations in the SPG7 gene vs controls
Measured: Inclusion
Secondary outcomes (1)
Mitochondrial calcium quantification after expression of a probe for calcium detection in patients with neurological symptoms and one or two mutations in the SPG7 gene vs controls
Measured: Inclusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Nov 2021
- Study start16 Nov 2021
- Primary completion26 Jan 2022
- Study completion26 Jan 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SPG7Studies of the same condition, open and under way.
- More trials run by University Hospital, MontpellierThe sponsor's other registered studies.
- 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 N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Montpellier
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05127967
- Sponsor's protocol ID
- RECHMPL20_0615
- Acronym
- CONSP-HET7
- Status last verified
- Feb 2023
- First submitted
- 14 Oct 2021
- Last updated
- 17 Feb 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phenotypic, Biological and Functional Consequences of Mutations in the SPG7 Gene at the Heterozygous State
- ClinicalTrials.gov ID
- NCT05127967
- Acronym / sponsor ID
- CONSP-HET7 / RECHMPL20_0615
- Conditions
- SPG7
- Keywords
- SPG7, Dominant, human, Drosophila, mitochondria
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- University Hospital, MontpellierUniversity, hospital or other
- Study start
- 16 Nov 2021 (actual)
- Primary completion
- 26 Jan 2022 (actual)
- Study completion
- 26 Jan 2022 (actual)
- First posted
- 19 Nov 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.
Paraplegin, encoded by the SPG7 gene, is an ATP-dependent mAAA protease located in the inner mitochondrial membrane. Its function is not fully understood. Mutations in the SPG7 gene are responsible for spastic paraplegia type 7. Although spastic paraplegia type 7 is considered to be a recessive disease, some clinical observations also point to a detrimental effect of a variant in SPG7 in the heterozygous state. Thus, the presence of a single mutated variant of the SPG7 gene could be a risk factor for the development of neurological diseases. This has important implications for genetic counseling of patients and for the understanding of the function of the SPG7 protein and the mechanisms of disease development.
Detailed description
Although spastic paraplegia type 7 is considered to be a recessive disease, some clinical observations also argue for a detrimental effect of a variant in SPG7 in the heterozygous state. Thus, the presence of a single mutated variant of the SPG7 gene could be a risk factor for the development of neurological diseases. This has important implications for genetic counseling of patients and for the understanding of the function of the SPG7 protein and the mechanisms of disease development. To date there have been no studies to specifically explore the pathogenic role of single heterozygous variants in the SPG7 gene.
The aim of this project is to fully characterize different models expressing single heterozygous SPG7 mutations in order to detect phenotypical, biological or functional alterations. In particular, the investigators will conduct analysis on fibroblasts from symptomatic patients with mutations in the SPG7 gene (homozygous, compound heterozygous or single heterozygous), and controls. Cellular models will be particularly useful in order to study an alteration in calcium homeostasis and in the response to ER stressors. In parallel, studies will be performed using the genetic animal model of Drosophila melanogaster.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Patients with neurological symptoms and two mutations in the SPG7 gene | Other | Other: Skin biopsySymptomatic patients with SPG7 mutations (homozygous or compound heterozygous) |
| Patients with neurological symptoms and one mutation in the SPG7 gene | Other | Other: Skin biopsyPatients presenting neurological symptoms corresponding to SPG7 disease (adult onset spastic ataxia with CPEO and/or optic atrophy) with only one mutation found in the SPG7 gene |
| Controls | Other | Other: Skin biopsyPatients without mutations in the SPG7 gene requiring spinal surgery because of a non-genetic neurologic disorders |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Age > or equal to 18 years
- Subject who is already undergoing neurosurgical intervention as part of the care pathway for an for an acquired, non-genetic neurological problem (e.g. herniated disc, narrow lumbar canal)
- Non-inclusion Criteria of cases
- Refusal to sign the written informed consent signed by the patient (or by his representative in case of a patient under guardianship.
- Patients with specific contraindications for skin biopsy current anticoagulant treatment; any pathologies that may cause a risk of bleeding (e.g. hemophiliacs)
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| Skin biopsyA skin biopsy involves taking a piece of skin to obtain cells (fibroblasts). Skin biopsy is a minimally invasive examination and a technically simple procedure performed with a 3mm diameter punch, or with a scalpel under local anesthesia (Lidocaine patch). The procedure can be done in a consultation office with strict asepsis. It lasts 15 minutes in total + the time to reach between putting on the lidocaine patch and performing the procedure. This biopsy will usually be done on the inside of the arm. In the majority of cases, it is not helpful to close the scar with stitches. | Other | Controls, Patients with neurological symptoms and one mutation in the SPG7 gene, Patients with neurological symptoms and two mutations in the SPG7 gene |
Primary outcome
Mitochondrial respiratory activity measured by Seahorse analyser and quantification of mADN vs nuclear AND in activity in patients with neurological symptoms and one or two mutations in the SPG7 gene vs controls
Time frame: Inclusion
Mitochondrial dimension and morphology by electronic microscopy and quantification of mitochondrial motility by direct imaging activity in patients with neurological symptoms and one or two mutations in the SPG7 gene vs controls
Time frame: Inclusion
1 secondary outcome
Mitochondrial calcium quantification after expression of a probe for calcium detection in patients with neurological symptoms and one or two mutations in the SPG7 gene vs controls
Time frame: Inclusion
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 17 Feb 2023.
Related trials for SPG7
Recruiting
Effects of a Supervised Rehabilitation Program on Disease Severity in Spastic Ataxias
Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay, Spastic Paraplegia 7
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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Skin biopsy in people with SPG7, run by University Hospital, Montpellier at 1 site in France.
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 14 inclusion and 0 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 17 Feb 2023. 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 France. 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.
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?
Mitochondrial respiratory activity measured by Seahorse analyser and quantification of mADN vs nuclear AND in activity in patients with neurological symptoms and one or two mutations in the SPG7 gene vs controls (time frame: Inclusion). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 17 Feb 2023.