Multiple SclerosisSMILENCT05627609
Sunlight-mediated Inter-organ Leukocyte Exchange
A study testing 311 nm narrowband UVB irradiation in people with Multiple Sclerosis, run by University Hospital Muenster at 1 site in Germany.
Trial summary
Ultraviolet B (UVB) irradiation induces regulatory immune cell types that may transmigrate from the skin to the blood and to the central nervous system and exert regulatory effects. Vitamin D deficiency-associated gene variants should reduce this effect if this is mediated by vitamin D. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- 311 nm narrowband UVB irradiation
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteGermany
- Study dates
- 21 Nov 2022to 14 Apr 2023
- 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 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- RRMS according to revised McDonald criteria (2017) or healthy volunteer
- Patients under treatment of natalizumab, teriflunomide, glatirameracetat or dimethyl fumarate for at least 4 weeks of therapy, or therapy-naïve patients will be included
Who cannot join
- Patients receiving treatment in the last 3 months of interferon-β, fingolimod, alemtuzumab, ocrelizumab, cladribine, ofatumumab, ozanimod, or ponesimod
- Vitamin D supplementation in the last 8 weeks
- UVB-narrowband contraindicated skin diseases (e.g., cutaneous neoplasia)
- Lacking the ability to stand on their own in the treatment chamber
- Signs of intolerance regarding UVB radiation
- Intake of UV-sensitive therapeutics
- Further autoimmune diseases (e.g., Morbus Crohn, psoriasis, neurodermatitis)
- Additional recreational or therapeutic UV radiation (e.g., solarium)
Trial locations and contacts
1 site in 1 country.
Germany1 site
University Hospital Muenster
Münster, North Rhine-Westphalia, 48149
About this study
Ultraviolet B (UVB) irradiation induces regulatory immune cell types that may transmigrate from the skin to the blood and to the central nervous system and exert regulatory effects. Vitamin D deficiency-associated gene variants should reduce this effect if this is mediated by vitamin D. For this study, participants will be irradiated with UVB for 4 weeks. Single cell RNA Sequencing will be performed on isolated immune cells from skin, blood and Cerebrospinal fluid (CSF), before and after irradiation.
Read the detailed description
The aim of this study will be to increase the Vitamin D3-serum concentrations in Multiple Sclerosis patients via UVB radiation with regard to different Vitamin D deficit-associated genotypes and analyse the effects of Vitamin D increase and UVB radiation, in general, on their immune cells. Participants of this study will be recruited from the pool of already registered MS patients at the department of neurology at the UKM and from resident practitioners of the Neuroimmunologisches Kompetenznetzwerk Münsterland. The UVB radiation of the participants will take place during wintertime to avoid any interference by ambient sunlight. As the participants will not take any supplements of Vitamin D, their serum concentration should be very low. The participants will be screened beforehand for their Vitamin D deficit-associated single nucleotide polymorphism and sorted into two groups depending on their calculated risk scores. The patients will also receive a clinical assessment in the department of neurology and dermatology and a cranial MRT. 17 patients each will be sorted into one of two groups: either Vitamin D deficiency high-risk or low-risk. The UVB influence on Vitamin D-serum concentration increases between those two groups should then be dependent on the associated genotypes. We will track those changes by taking blood samples before and after the radiation. We will also take samples of the skin and, for participants opting in, cerebrospinal fluid (CSF). This will allow us to isolate single cells from each of the three compartments and sequence them on a RNA transcriptomic level following the 10x workflow. UVB radiation will induce immunomodulating effects in the skin and Vitamin D was shown to be one of those effects, as its synthesis is initiated by UVB radiation and its binding to Vitamin D receptors renders immune cells more regulatory. If differences in immune cell alterations were found between the two groups of risk scores, they should be attributed to the associated genotypes, shedding new light on the influence of Vitamin D on the pathogenesis of MS patients and on the immune system in general.
By utilizing single-cell RNA-sequencing on isolated immune cells of those three compartments, before and after the UVB radiation, we will be able to have a relatively unbiased approach to investigating the influence of UVB radiation and, separately, Vitamin D on the immune cells. Specific cell signatures of sequenced immune cells from the three compartments will allow us to track the migration of the induced cells from the skin through the blood and into the CSF. Additionally, CSF and serum isolated from blood will be assessed for Epstein-Barr-Virus antibody titers and extracellular vesicles. All this data will contribute to our multidimensional analysis using bioinformatics workflows based on linear methods such as principal components analysis and non-linear tools based on neural networks and Bayesian variational inference.
- Conditions
- Multiple Sclerosis
- Being tested
- 311 nm narrowband UVB irradiation
- Keywords
- UVB, scRNAseq
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
311 nm narrowband UVB irradiationDevice
Participants will be irradiated with 311nm UVB for 5 days per week and 4 weeks in total.
| Study group | Role | What they receive |
|---|---|---|
| Participants with high Vitamin D genotype risk score | Experimental | Not described Receives: Device: 311 nm narrowband UVB irradiation |
| PArticipants with low Vitamin D genotype risk score | Experimental | Not described Receives: Device: 311 nm narrowband UVB irradiation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Vitamin D3 serum concentration (ng/mL)
Changes in Vitamin D3 serum concentration (ng/mL) of RRMS patients with regard to different Vitamin D3 deficit-associated genotypes before and after UVB-narrowband radiation.
Measured: 4 weeks
Secondary outcomes (1)
single-cell RNA sequencing
By utilizing single-cell RNA sequencing of immune cells from the skin and blood and even potentially the cerebrospinal fluid (CSF) we want to analyze the phenotype of UVB-induced immune cells and potentially track their migration from the skin through the peripheral blood into the CSF. If any of the witnessed immune regulatory effects in those three compartments can be attributed to the increase of Vitamin D3 through UVB radiation, we should be able to differentiate those effects among the different genotypes. Since MS risk and severity correlate with EBV infection and infectious mononucleosis, we will also measure EBV antibody titers before and after UVB radiation in blood and CSF.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Nov 2022
- Study start21 Nov 2022
- Primary completion14 Apr 2023
- Study completion14 Apr 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple SclerosisStudies 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 N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital Muenster
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Nicholas Schwab, University Hospital Muenster
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05627609
- Sponsor's protocol ID
- SMILE-2022-439-f-S
- Acronym
- SMILE
- Status last verified
- May 2023
- First submitted
- 16 Nov 2022
- Last updated
- 9 May 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sunlight-mediated Inter-organ Leukocyte Exchange
- ClinicalTrials.gov ID
- NCT05627609
- Acronym / sponsor ID
- SMILE / SMILE-2022-439-f-S
- Conditions
- Multiple Sclerosis
- Keywords
- UVB, scRNAseq
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- University Hospital MuensterUniversity, hospital or other
- Study start
- 21 Nov 2022 (actual)
- Primary completion
- 14 Apr 2023 (actual)
- Study completion
- 14 Apr 2023 (actual)
- First posted
- 25 Nov 2022 (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.
Ultraviolet B (UVB) irradiation induces regulatory immune cell types that may transmigrate from the skin to the blood and to the central nervous system and exert regulatory effects. Vitamin D deficiency-associated gene variants should reduce this effect if this is mediated by vitamin D. For this study, participants will be irradiated with UVB for 4 weeks. Single cell RNA Sequencing will be performed on isolated immune cells from skin, blood and Cerebrospinal fluid (CSF), before and after irradiation.
Detailed description
The aim of this study will be to increase the Vitamin D3-serum concentrations in Multiple Sclerosis patients via UVB radiation with regard to different Vitamin D deficit-associated genotypes and analyse the effects of Vitamin D increase and UVB radiation, in general, on their immune cells. Participants of this study will be recruited from the pool of already registered MS patients at the department of neurology at the UKM and from resident practitioners of the Neuroimmunologisches Kompetenznetzwerk Münsterland. The UVB radiation of the participants will take place during wintertime to avoid any interference by ambient sunlight. As the participants will not take any supplements of Vitamin D, their serum concentration should be very low. The participants will be screened beforehand for their Vitamin D deficit-associated single nucleotide polymorphism and sorted into two groups depending on their calculated risk scores. The patients will also receive a clinical assessment in the department of neurology and dermatology and a cranial MRT. 17 patients each will be sorted into one of two groups: either Vitamin D deficiency high-risk or low-risk. The UVB influence on Vitamin D-serum concentration increases between those two groups should then be dependent on the associated genotypes. We will track those changes by taking blood samples before and after the radiation. We will also take samples of the skin and, for participants opting in, cerebrospinal fluid (CSF). This will allow us to isolate single cells from each of the three compartments and sequence them on a RNA transcriptomic level following the 10x workflow. UVB radiation will induce immunomodulating effects in the skin and Vitamin D was shown to be one of those effects, as its synthesis is initiated by UVB radiation and its binding to Vitamin D receptors renders immune cells more regulatory. If differences in immune cell alterations were found between the two groups of risk scores, they should be attributed to the associated genotypes, shedding new light on the influence of Vitamin D on the pathogenesis of MS patients and on the immune system in general.
By utilizing single-cell RNA-sequencing on isolated immune cells of those three compartments, before and after the UVB radiation, we will be able to have a relatively unbiased approach to investigating the influence of UVB radiation and, separately, Vitamin D on the immune cells. Specific cell signatures of sequenced immune cells from the three compartments will allow us to track the migration of the induced cells from the skin through the blood and into the CSF. Additionally, CSF and serum isolated from blood will be assessed for Epstein-Barr-Virus antibody titers and extracellular vesicles. All this data will contribute to our multidimensional analysis using bioinformatics workflows based on linear methods such as principal components analysis and non-linear tools based on neural networks and Bayesian variational inference.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Participants with high Vitamin D genotype risk score | Experimental | Device: 311 nm narrowband UVB irradiation |
| PArticipants with low Vitamin D genotype risk score | Experimental | Device: 311 nm narrowband UVB irradiation |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- RRMS according to revised McDonald criteria (2017) or healthy volunteer
- Patients under treatment of natalizumab, teriflunomide, glatirameracetat or dimethyl fumarate for at least 4 weeks of therapy, or therapy-naïve patients will be included
Key exclusion criteria (8 listed)
- Patients receiving treatment in the last 3 months of interferon-β, fingolimod, alemtuzumab, ocrelizumab, cladribine, ofatumumab, ozanimod, or ponesimod
- Vitamin D supplementation in the last 8 weeks
- UVB-narrowband contraindicated skin diseases (e.g., cutaneous neoplasia)
- Lacking the ability to stand on their own in the treatment chamber
- Signs of intolerance regarding UVB radiation
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 |
|---|---|---|
| 311 nm narrowband UVB irradiationParticipants will be irradiated with 311nm UVB for 5 days per week and 4 weeks in total. | Device | PArticipants with low Vitamin D genotype risk score, Participants with high Vitamin D genotype risk score |
Primary outcome
Vitamin D3 serum concentration (ng/mL)
Time frame: 4 weeks
Changes in Vitamin D3 serum concentration (ng/mL) of RRMS patients with regard to different Vitamin D3 deficit-associated genotypes before and after UVB-narrowband radiation.
1 secondary outcome
single-cell RNA sequencing
Time frame: 1 year
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 9 May 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.
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 311 nm narrowband UVB irradiation in people with Multiple Sclerosis, run by University Hospital Muenster at 1 site in Germany.
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 8 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 9 May 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 Germany. 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?
Vitamin D3 serum concentration (ng/mL) (time frame: 4 weeks). 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 9 May 2023.