Multiple SclerosisNCT06290453
The Regulatory Role of miRNA 27 Follistatin Like Protein-1 Gene in Multiple Scelerosis
An observational study of Multiple Sclerosis, run by Assiut University.
Trial summary
Multiple sclerosis (MS) is a neurodegenerative disease characterized by demyelination of the central nervous system. Young women between the ages of 20 and 40 are primarily targeted by this disabling disorder. Till now there are no sufficient mechanisms to explain the pathophysiology of multiple sclerosis. Read more about this study
- Who is it for?
- Ages 20 to 45 years, women only
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- micro RNA 27- FLP1 gene expression, The Expanded Disability Status Scale (EDSS) and Electrophysiological assessment:
- How many people
- 60 participants
- Where
- No sites listed yet
- Study dates
- Mar 2024to Mar 2026
- 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 20 to 45 years
- Women only
- Adult
Study population: Study subjects: 1. Inclusion criteria: 1. Patients diagnosed with MS based on the revised McDonald criteria. 2. Female patients will only be included. 3. 20- 45 years old. 4. Drug naïve. 2. Exclusion criteria: 1. Patients with other neurodegenerative and autoimmune disorders. 2. Pregnant females. 3. Co-existing chronic hypertension, diabetes, and epilepsy 4. Chronic renal or hepatic diseases
Who may be able to join
- Patients diagnosed with MS based on the revised McDonald criteria.
- Female patients will only be included.
- 20- 45 years old.
- Drug naïve.
Who cannot join
- 1. Patients with other neurodegenerative and autoimmune disorders. 2. Pregnant females. 3. Co-existing chronic hypertension, diabetes, and epilepsy 4. chronic renal or hepatic diseases
Trial locations and contacts
No sites are listed yet.
About this study
Official title: The Regulatory Role of miRNA 27 and Follistatin Like Protein-1 Gene in the Pathophysiology of Multiple Sclerosis Patients.
Multiple sclerosis (MS) is a neurodegenerative disease characterized by demyelination of the central nervous system. Young women between the ages of 20 and 40 are primarily targeted by this disabling disorder. Till now there are no sufficient mechanisms to explain the pathophysiology of multiple sclerosis.
Read the detailed description
Neuroinflammation has been implicated in the initiation and progression of several central nervous system (CNS) disorders, including multiple sclerosis. Microglia and astrocytes are essential in neural development, maintenance of synaptic connections, and homeostasis in a healthy brain.
Recent researchers have discovered that microRNAs (miRNAs) contribute to the pathophysiology of MS, primarily influencing glial cells and the immune cells in the periphery. In recent years, miRNAs have become more prevalent as inflammation and demyelination process regulators in MS.
miRNAs are naturally occurring, non-coding RNA molecules (21-25 nucleotides). miRNAs play a part in the post-transcriptional regulation of gene expression and silencing of RNA. miRNAs have been discovered to control some physiological processes, as apoptosis, proliferation, differentiation, and development.
Measurement of circulating miRNAs in MS patients' peripheral blood is one of the promising approaches as it can be a non-invasive tool to explain its pathogenesis. miRNAs are remarkably stable in bodily fluids and are relatively simple to collect and quantify. Moreover, a novel approach to therapy may be based on methods that regulate the activity of miRNAs.
Several miRNAs particularly miR-27 have been reportedly involved in regulating myelination in the central nervous system. However, the role of micro RNAs in generation or progression of MS remains elusive.
Follistatin-like protein-1 (FSTL1) was first identified as a transforming growth factor β1-inducible protein. In the last decade, FSTL1 has been identified as a novel inflammatory protein. FSTL1 is a glycoprotein rich in cysteine (SPARC) family. FSTL1 is elevated in various inflammatory conditions and decreased during treatment.
Moreover, a variety of studies suggest that targeting of FSTL1 may be useful in the treatment of diseases in which inflammation plays a central role. Recent studies revealed a substantial connection between FSTL1 and micro-RNA 27 levels and demonstrated that the regulatory effects of miR-27 in some inflammatory conditions may be exerted by targeting FSTL1.
This study aims to investigate the expression patterns of miR-27 and Follistatin like 1 gene in peripheral blood samples of MS patients. As, we hypothesize that miR-27 and its target gene (FSTL1) may serve important roles in the pathogenesis of MS.
- Conditions
- Multiple Sclerosis
- Being tested
- micro RNA 27- FLP1 gene expression, The Expanded Disability Status Scale (EDSS), Electrophysiological assessment:, MRI examination MRI brain:
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
micro RNA 27- FLP1 gene expressionDiagnostic test
From each participant, 2 mL of blood will be drawn and store at 25-degree C. The expression of miRNA-27 and FLP1 gene will be measured using real time PCR.
Relative expression values will be normalised to the housekeeping gene GAPDH. The comparative cycle threshold (Ct) approach will be used to measure the relative expression of miRNA 27 and FLP1 gene. Then, using the equation -ΔΔCT, the fold change of each gene will be determined
The Expanded Disability Status Scale (EDSS)Diagnostic test
The Expanded Disability Status Scale (EDSS) is a way of measuring how much someone is affected by their MS. Neurologists use it to monitor changes in the level of someone's disability over time. The EDSS has a range from 0 to 10.
Zero points is normal neurological examination. 10 points shows the MS-related death cases. Patients with EDSS score up to 5 are fully ambulatory patients.
Electrophysiological assessment:Diagnostic test
Electromyography and nerve conduction velocity will be performed for all MS patients.
MRI examination MRI brain:Diagnostic test
will be done on all MS patients to detect the number, the site, and the enhancement of lesions
| Study group | Role | What they receive |
|---|---|---|
| Multiple sclerosis patients (MS) | included 40 patients with newly discovered MS (duration of the disease is 3 years or less) and diagnosed according to the revised McDonald criteria. The patients will be recruited from the neurology department of Assiut University Hospital.
MS patients will be further subdivided into two subgroups: 20 patients with RRMS and 20 patients with Progressive MS group. Receives: Diagnostic Test: micro RNA 27- FLP1 gene expression; Diagnostic Test: The Expanded Disability Status Scale (EDSS); Diagnostic Test: Electrophysiological assessment:; Diagnostic Test: MRI examination MRI brain: | |
| Control (C) | Group II: included 20 healthy individuals who will be age- and sex-matched as a control group, with no history of any neurological or autoimmune disease. Receives: Diagnostic Test: micro RNA 27- FLP1 gene expression |
What is being measured
The primary outcome is the main question the study is designed to answer.
• To measure the levels of miR-27 expression and its target gene (FSTL1) in progressive MS and relapsing-remitting multiple sclerosis (RRMS) patients.
RNA extraction Reverse Transcription polymerase chain reaction (RT-PCR) analysis:
Measured: 1 month
Secondary outcomes (1)
To correlate the levels of expression of miR-27 expression and its target gene (FSTL1) relative to the severity of symptoms of MD patients.
Statistical analysis: Pearson correlation for parametric data, spearman correlation for non-parametric data.
Measured: 1 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Mar 2024
- Study startMar 2024 (estimated)
- Primary completionMar 2025 (estimated)
- Study completionMar 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- More trials run by Assiut UniversityThe 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
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assiut University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Rasha Mohammed Ali, Assiut University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06290453
- Sponsor's protocol ID
- AOGR
- Status last verified
- Feb 2024
- First submitted
- 20 Feb 2024
- Last updated
- 4 Mar 2024
- Results posted
- No
Publications
Chaly Y, Marinov AD, Oxburgh L, Bushnell DS, Hirsch R. FSTL1 promotes arthritis in mice by enhancing inflammatory cytokine/chemokine expression. Arthritis Rheum. 2012 Apr;64(4):1082-8. doi: 10.1002/art.33422. Epub 2011 Oct 17.
PubMed 22006268Chen L, Lu Q, Chen J, Feng R, Yang C. Upregulating miR-27a-3p inhibits cell proliferation and inflammation of rheumatoid arthritis synovial fibroblasts through targeting toll-like receptor 5. Exp Ther Med. 2021 Nov;22(5):1227. doi: 10.3892/etm.2021.10661. Epub 2021 Aug 27.
PubMed 34539823Mattiotti A, Prakash S, Barnett P, van den Hoff MJB. Follistatin-like 1 in development and human diseases. Cell Mol Life Sci. 2018 Jul;75(13):2339-2354. doi: 10.1007/s00018-018-2805-0. Epub 2018 Mar 29.
PubMed 29594389Pachner AR. The Neuroimmunology of Multiple Sclerosis: Fictions and Facts. Front Neurol. 2022 Feb 7;12:796378. doi: 10.3389/fneur.2021.796378. eCollection 2021.
PubMed 35197914Shi DL, Shi GR, Xie J, Du XZ, Yang H. MicroRNA-27a Inhibits Cell Migration and Invasion of Fibroblast-Like Synoviocytes by Targeting Follistatin-Like Protein 1 in Rheumatoid Arthritis. Mol Cells. 2016 Aug 31;39(8):611-8. doi: 10.14348/molcells.2016.0103. Epub 2016 Aug 8.
PubMed 27498552Sun M, You H, Hu X, Luo Y, Zhang Z, Song Y, An J, Lu H. Microglia-Astrocyte Interaction in Neural Development and Neural Pathogenesis. Cells. 2023 Jul 27;12(15):1942. doi: 10.3390/cells12151942.
PubMed 37566021Zheleznyakova GY, Piket E, Needhamsen M, Hagemann-Jensen M, Ekman D, Han Y, James T, Khademi M, Al Nimer F, Scicluna P, Huang J, Kockum I, Faridani OR, Olsson T, Piehl F, Jagodic M. Small noncoding RNA profiling across cellular and biofluid compartments and their implications for multiple sclerosis immunopathology. Proc Natl Acad Sci U S A. 2021 Apr 27;118(17):e2011574118. doi: 10.1073/pnas.2011574118.
PubMed 33879606Yang J, Hamade M, Wu Q, Wang Q, Axtell R, Giri S, Mao-Draayer Y. Current and Future Biomarkers in Multiple Sclerosis. Int J Mol Sci. 2022 May 24;23(11):5877. doi: 10.3390/ijms23115877.
PubMed 35682558Tsuchikawa Y, Kamei N, Sanada Y, Nakamae T, Harada T, Imaizumi K, Akimoto T, Miyaki S, Adachi N. Deficiency of MicroRNA-23-27-24 Clusters Exhibits the Impairment of Myelination in the Central Nervous System. Neural Plast. 2023 Mar 22;2023:8938674. doi: 10.1155/2023/8938674. eCollection 2023.
PubMed 37006814
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Regulatory Role of miRNA 27 and Follistatin Like Protein-1 Gene in the Pathophysiology of Multiple Sclerosis Patients.
- ClinicalTrials.gov ID
- NCT06290453
- Acronym / sponsor ID
- AOGR
- Conditions
- Multiple Sclerosis
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Assiut UniversityUniversity, hospital or other
- Study start
- Mar 2024 (estimated)
- Primary completion
- Mar 2025 (estimated)
- Study completion
- Mar 2026 (estimated)
- First posted
- 4 Mar 2024 (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.
Multiple sclerosis (MS) is a neurodegenerative disease characterized by demyelination of the central nervous system. Young women between the ages of 20 and 40 are primarily targeted by this disabling disorder. Till now there are no sufficient mechanisms to explain the pathophysiology of multiple sclerosis.
Detailed description
Neuroinflammation has been implicated in the initiation and progression of several central nervous system (CNS) disorders, including multiple sclerosis. Microglia and astrocytes are essential in neural development, maintenance of synaptic connections, and homeostasis in a healthy brain.
Recent researchers have discovered that microRNAs (miRNAs) contribute to the pathophysiology of MS, primarily influencing glial cells and the immune cells in the periphery. In recent years, miRNAs have become more prevalent as inflammation and demyelination process regulators in MS.
miRNAs are naturally occurring, non-coding RNA molecules (21-25 nucleotides). miRNAs play a part in the post-transcriptional regulation of gene expression and silencing of RNA. miRNAs have been discovered to control some physiological processes, as apoptosis, proliferation, differentiation, and development.
Measurement of circulating miRNAs in MS patients' peripheral blood is one of the promising approaches as it can be a non-invasive tool to explain its pathogenesis. miRNAs are remarkably stable in bodily fluids and are relatively simple to collect and quantify. Moreover, a novel approach to therapy may be based on methods that regulate the activity of miRNAs.
Several miRNAs particularly miR-27 have been reportedly involved in regulating myelination in the central nervous system. However, the role of micro RNAs in generation or progression of MS remains elusive.
Follistatin-like protein-1 (FSTL1) was first identified as a transforming growth factor β1-inducible protein. In the last decade, FSTL1 has been identified as a novel inflammatory protein. FSTL1 is a glycoprotein rich in cysteine (SPARC) family. FSTL1 is elevated in various inflammatory conditions and decreased during treatment.
Moreover, a variety of studies suggest that targeting of FSTL1 may be useful in the treatment of diseases in which inflammation plays a central role. Recent studies revealed a substantial connection between FSTL1 and micro-RNA 27 levels and demonstrated that the regulatory effects of miR-27 in some inflammatory conditions may be exerted by targeting FSTL1.
This study aims to investigate the expression patterns of miR-27 and Follistatin like 1 gene in peripheral blood samples of MS patients. As, we hypothesize that miR-27 and its target gene (FSTL1) may serve important roles in the pathogenesis of MS.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Multiple sclerosis patients (MS) | – | Diagnostic Test: micro RNA 27- FLP1 gene expression, Diagnostic Test: The Expanded Disability Status Scale (EDSS), Diagnostic Test: Electrophysiological assessment:, Diagnostic Test: MRI examination MRI brain:included 40 patients with newly discovered MS (duration of the disease is 3 years or less) and diagnosed according to the revised McDonald criteria. The patients will be recruited from the neurology department of Assiut University Hospital. MS patients will be further subdivided into two subgroups: 20 patients with RRMS and 20 patients with Progressive MS group. |
| Control (C) | – | Diagnostic Test: micro RNA 27- FLP1 gene expressionGroup II: included 20 healthy individuals who will be age- and sex-matched as a control group, with no history of any neurological or autoimmune disease. |
Who may qualify
- Ages
- 20 to 45 years
- Sex
- Female only
- Age groups
- Adult
- Study population
- Study subjects: 1. Inclusion criteria: 1. Patients diagnosed with MS based on the revised McDonald criteria. 2. Female patients will only be included. 3. 20- 45 years old. 4. Drug naïve. 2. Exclusion criteria: 1. Patients with other neurodegenerative and autoimmune disorders. 2. Pregnant females. 3. Co-existing chronic hypertension, diabetes, and epilepsy 4. Chronic renal or hepatic diseases
Key inclusion criteria (4 listed)
- Patients diagnosed with MS based on the revised McDonald criteria.
- Female patients will only be included.
- 20- 45 years old.
- Drug naïve.
Key exclusion criteria (1 listed)
- 1. Patients with other neurodegenerative and autoimmune disorders. 2. Pregnant females. 3. Co-existing chronic hypertension, diabetes, and epilepsy 4. chronic renal or hepatic diseases
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 |
|---|---|---|
| micro RNA 27- FLP1 gene expressionFrom each participant, 2 mL of blood will be drawn and store at 25-degree C. The expression of miRNA-27 and FLP1 gene will be measured using real time PCR. Relative expression values will be normalised to the housekeeping gene GAPDH. The comparative cycle threshold (Ct) approach will be used to measure the relative expression of miRNA 27 and FLP1 gene. Then, using the equation -ΔΔCT, the fold change of each gene will be determined | Diagnostic test | Control (C), Multiple sclerosis patients (MS) |
| The Expanded Disability Status Scale (EDSS)The Expanded Disability Status Scale (EDSS) is a way of measuring how much someone is affected by their MS. Neurologists use it to monitor changes in the level of someone's disability over time. The EDSS has a range from 0 to 10. Zero points is normal neurological examination. 10 points shows the MS-related death cases. Patients with EDSS score up to 5 are fully ambulatory patients. | Diagnostic test | Multiple sclerosis patients (MS) |
| Electrophysiological assessment:Electromyography and nerve conduction velocity will be performed for all MS patients. | Diagnostic test | Multiple sclerosis patients (MS) |
| MRI examination MRI brain:will be done on all MS patients to detect the number, the site, and the enhancement of lesions | Diagnostic test | Multiple sclerosis patients (MS) |
Primary outcome
• To measure the levels of miR-27 expression and its target gene (FSTL1) in progressive MS and relapsing-remitting multiple sclerosis (RRMS) patients.
Time frame: 1 month
RNA extraction Reverse Transcription polymerase chain reaction (RT-PCR) analysis:
1 secondary outcome
To correlate the levels of expression of miR-27 expression and its target gene (FSTL1) relative to the severity of symptoms of MD patients.
Time frame: 1 month
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2024.
- Results publication: PubMed 22006268Chaly Y, Marinov AD, Oxburgh L, Bushnell DS, Hirsch R. FSTL1 promotes arthritis in mice by enhancing inflammatory cytokine/chemokine expression. Arthritis Rheum. 2012 Apr;64(4):1082-8. doi: 10.1002/art.33422. Epub 2011 Oct 17.
- Results publication: PubMed 34539823Chen L, Lu Q, Chen J, Feng R, Yang C. Upregulating miR-27a-3p inhibits cell proliferation and inflammation of rheumatoid arthritis synovial fibroblasts through targeting toll-like receptor 5. Exp Ther Med. 2021 Nov;22(5):1227. doi: 10.3892/etm.2021.10661. Epub 2021 Aug 27.
- Results publication: PubMed 29594389Mattiotti A, Prakash S, Barnett P, van den Hoff MJB. Follistatin-like 1 in development and human diseases. Cell Mol Life Sci. 2018 Jul;75(13):2339-2354. doi: 10.1007/s00018-018-2805-0. Epub 2018 Mar 29.
- Results publication: PubMed 35197914Pachner AR. The Neuroimmunology of Multiple Sclerosis: Fictions and Facts. Front Neurol. 2022 Feb 7;12:796378. doi: 10.3389/fneur.2021.796378. eCollection 2021.
- Results publication: PubMed 27498552Shi DL, Shi GR, Xie J, Du XZ, Yang H. MicroRNA-27a Inhibits Cell Migration and Invasion of Fibroblast-Like Synoviocytes by Targeting Follistatin-Like Protein 1 in Rheumatoid Arthritis. Mol Cells. 2016 Aug 31;39(8):611-8. doi: 10.14348/molcells.2016.0103. Epub 2016 Aug 8.
- Results publication: PubMed 37566021Sun M, You H, Hu X, Luo Y, Zhang Z, Song Y, An J, Lu H. Microglia-Astrocyte Interaction in Neural Development and Neural Pathogenesis. Cells. 2023 Jul 27;12(15):1942. doi: 10.3390/cells12151942.
- Results publication: PubMed 33879606Zheleznyakova GY, Piket E, Needhamsen M, Hagemann-Jensen M, Ekman D, Han Y, James T, Khademi M, Al Nimer F, Scicluna P, Huang J, Kockum I, Faridani OR, Olsson T, Piehl F, Jagodic M. Small noncoding RNA profiling across cellular and biofluid compartments and their implications for multiple sclerosis immunopathology. Proc Natl Acad Sci U S A. 2021 Apr 27;118(17):e2011574118. doi: 10.1073/pnas.2011574118.
- Results publication: PubMed 35682558Yang J, Hamade M, Wu Q, Wang Q, Axtell R, Giri S, Mao-Draayer Y. Current and Future Biomarkers in Multiple Sclerosis. Int J Mol Sci. 2022 May 24;23(11):5877. doi: 10.3390/ijms23115877.
- Results publication: PubMed 37006814Tsuchikawa Y, Kamei N, Sanada Y, Nakamae T, Harada T, Imaizumi K, Akimoto T, Miyaki S, Adachi N. Deficiency of MicroRNA-23-27-24 Clusters Exhibits the Impairment of Myelination in the Central Nervous System. Neural Plast. 2023 Mar 22;2023:8938674. doi: 10.1155/2023/8938674. eCollection 2023.
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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.
Questions about this trial
What is this clinical trial studying?
An observational study of Multiple Sclerosis, run by Assiut University.
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 4 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 4 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
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 Rasha Mohammed, Lecturer (01010024021, rasha.mohamed94@yahoo.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
• To measure the levels of miR-27 expression and its target gene (FSTL1) in progressive MS and relapsing-remitting multiple sclerosis (RRMS) patients. (time frame: 1 month). 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 NCT06290453, which also lists 9 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 4 Mar 2024; AzTrials last refreshed its copy on 8 Nov 2026.