Spinal Muscular AtrophyCircSMANCT05760209
SMN Circular RNAs as Potential New Targets and Biomarkers for SMA
An observational study of Spinal Muscular Atrophy, run by Fondazione Policlinico Universitario Agostino Gemelli IRCCS at 1 site in Italy.
Trial summary
Spinal Muscular Atrophy (SMA) is a life-threatening disease in infancy that is caused by inactivating mutations in the Survival Motor Neuron 1 (SMN1) gene1,2. SMN1 mutations lead to deficiency in SMN protein, which results in degeneration of motor neurons in the spinal cord, progressive muscle weakness and atrophy. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Spinal Muscular Atrophy
- How many people
- 30 participants
- Where
- 1 siteItaly
- Study dates
- 22 Jul 2021to 21 Jul 2024
- Phase
- Observational
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: patients with SMA trewated according to standards of care
Who may be able to join
- Genetic diagnosis of SMA, without any restrictions for phenotype (i.e. presymptomatic patients, SMA 0, SMA I, SMA II, SMA III, SMA IV patients), number of SMN2, age or gender.
- Treatment with Nusinersen or Risdiplam or Zolgensma.
Who cannot join
- unable to provide consent
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
Policlinico gemelli
Rome
Eugenio Mercuri, 063015 ext. 5340, eugeniomaria.mercuri@policlinicogemelli.it
About this study
Official title: SMN Circular RNAs as Potential New Targets and Biomarkers for the Therapeutic Response in Spinal Muscular Atrophy
Spinal Muscular Atrophy (SMA) is a life-threatening disease in infancy that is caused by inactivating mutations in the Survival Motor Neuron 1 (SMN1) gene1,2. SMN1 mutations lead to deficiency in SMN protein, which results in degeneration of motor neurons in the spinal cord, progressive muscle weakness and atrophy. The almost identical SMN2 gene does not suffice SMN function, because skipping of exon 7 in its mRNA yields an unstable protein. Nevertheless, SMN2 represents a disease modifier gene and increasing its expression or rescuing its splicing defect have long been considered elective strategies for SMA1,2. After substantial translational research efforts, the first therapies eliciting clinical benefits for SMA patients have recently become available3. Nusinersen, an antisense oligonucleotide (ASO), and Risdiplasm, a small molecule, bind the SMN2 RNA and promote splicing of exon 7. On the other hand, Zolgesma, an adeno-associated virus delivering the SMN1 gene (scAAV9-SMN), bypasses the need to correct the splicing defect. Nevertheless, none of these therapies currently represents a complete cure for patients, because not all of them respond equally and in a significant portion of patients the symptoms are attenuated but not corrected3. It is believed that early treatment, possibly at a pre-symptomatic stage, would positively affect the clinical response and may significantly improve patient's management. However, another critical point is the current lack of information on the long-term efficacy and safety of the current treatments4. In this scenario, it is likely that further elucidation of the biological functions of the SMN genes and the identification of robust biomarkers for stratification of patients will set the ground for more "personalized" therapies, which may account for the clinical variability observed in patients and help improving the therapies in use.
Read the detailed description
This project aims at investigating the potential value of SMN circRNAs as biomarkers of SMA, in terms of prediction of disease severity and response to therapeutic treatments.
In particular, we aim to:
- Evaluate the potential of SMN circRNAs as biomarkers of SMA clinical outcome. We will evaluate which SMN circRNAs are released in body fluids of SMA patients undergoing treatments and whether they display prognostic power as predictors of disease progression and clinical response to therapies.
- Perform a prospective analysis of SMN circRNAs expression in pre-symptomatic SMA patients. We will analyze the expression levels of SMN circRNAs in body fluids of SMA patients identified by neonatal genetic screening.
The results of our project may identify new tools to better stratify SMA patients and to improve the efficacy of the currently available treatments for this disease.
- Conditions
- Spinal Muscular Atrophy
- Keywords
- biomarkers, spinal muscular atrophy; outcome
- Medical subject headings
- Muscular Atrophy, Spinal
What is being measured
The primary outcome is the main question the study is designed to answer.
survival motor neuron (SMN) circular RNA
biomarker
Measured: 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Mar 2023
- Study start22 Jul 2021
- Primary completion21 Jul 2024 (estimated)
- Study completion21 Jul 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Spinal Muscular AtrophyStudies of the same condition, open and under way.
- More trials run by Fondazione Policlinico Universitario Agostino Gemelli IRCCSThe 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Eugenio Mercuri, Principal investigator, F Policlinico Gemelli IRCCS
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05760209
- Sponsor's protocol ID
- 4348
- Acronym
- CircSMA
- Status last verified
- Feb 2023
- First submitted
- 27 Feb 2023
- Last updated
- 8 Mar 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: aggregate data only
Study at a glance
From the registry record, last updated by the sponsor on 8 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- SMN Circular RNAs as Potential New Targets and Biomarkers for the Therapeutic Response in Spinal Muscular Atrophy
- ClinicalTrials.gov ID
- NCT05760209
- Acronym / sponsor ID
- CircSMA / 4348
- Conditions
- Spinal Muscular Atrophy
- Keywords
- biomarkers, spinal muscular atrophy; outcome
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Fondazione Policlinico Universitario Agostino Gemelli IRCCSUniversity, hospital or other
- Study start
- 22 Jul 2021 (actual)
- Primary completion
- 21 Jul 2024 (estimated)
- Study completion
- 21 Jul 2024 (estimated)
- First posted
- 8 Mar 2023 (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.
Spinal Muscular Atrophy (SMA) is a life-threatening disease in infancy that is caused by inactivating mutations in the Survival Motor Neuron 1 (SMN1) gene1,2. SMN1 mutations lead to deficiency in SMN protein, which results in degeneration of motor neurons in the spinal cord, progressive muscle weakness and atrophy. The almost identical SMN2 gene does not suffice SMN function, because skipping of exon 7 in its mRNA yields an unstable protein. Nevertheless, SMN2 represents a disease modifier gene and increasing its expression or rescuing its splicing defect have long been considered elective strategies for SMA1,2. After substantial translational research efforts, the first therapies eliciting clinical benefits for SMA patients have recently become available3. Nusinersen, an antisense oligonucleotide (ASO), and Risdiplasm, a small molecule, bind the SMN2 RNA and promote splicing of exon 7. On the other hand, Zolgesma, an adeno-associated virus delivering the SMN1 gene (scAAV9-SMN), bypasses the need to correct the splicing defect. Nevertheless, none of these therapies currently represents a complete cure for patients, because not all of them respond equally and in a significant portion of patients the symptoms are attenuated but not corrected3. It is believed that early treatment, possibly at a pre-symptomatic stage, would positively affect the clinical response and may significantly improve patient's management. However, another critical point is the current lack of information on the long-term efficacy and safety of the current treatments4. In this scenario, it is likely that further elucidation of the biological functions of the SMN genes and the identification of robust biomarkers for stratification of patients will set the ground for more "personalized" therapies, which may account for the clinical variability observed in patients and help improving the therapies in use.
Detailed description
This project aims at investigating the potential value of SMN circRNAs as biomarkers of SMA, in terms of prediction of disease severity and response to therapeutic treatments.
In particular, we aim to:
- Evaluate the potential of SMN circRNAs as biomarkers of SMA clinical outcome. We will evaluate which SMN circRNAs are released in body fluids of SMA patients undergoing treatments and whether they display prognostic power as predictors of disease progression and clinical response to therapies.
- Perform a prospective analysis of SMN circRNAs expression in pre-symptomatic SMA patients. We will analyze the expression levels of SMN circRNAs in body fluids of SMA patients identified by neonatal genetic screening.
The results of our project may identify new tools to better stratify SMA patients and to improve the efficacy of the currently available treatments for this disease.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- patients with SMA trewated according to standards of care
Key inclusion criteria (2 listed)
- Genetic diagnosis of SMA, without any restrictions for phenotype (i.e. presymptomatic patients, SMA 0, SMA I, SMA II, SMA III, SMA IV patients), number of SMN2, age or gender.
- Treatment with Nusinersen or Risdiplam or Zolgensma.
Key exclusion criteria (1 listed)
- unable to provide consent
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
survival motor neuron (SMN) circular RNA
Time frame: 36 months
biomarker
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Mar 2023.
- Individual participant dataSharing planned: No. aggregate data only
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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.
Eugenio Mercuri principal investigator
F Policlinico Gemelli IRCCS
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Spinal Muscular Atrophy, run by Fondazione Policlinico Universitario Agostino Gemelli IRCCS 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 2 inclusion and 1 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: status not confirmed, as of the sponsor's last update on 8 Mar 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 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.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Eugenio Mercuri, MD (063015 ext. 5340, eugeniomaria.mercuri@policlinicogemelli.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
survival motor neuron (SMN) circular RNA (time frame: 36 months). 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 8 Mar 2023.