Multiple SclerosisTSPONCT03850301
Validation of the 18 kiloDalton Translocator Protein (TSPO) as a Novel Neuroimmunodulatory Target
A study testing XBD173 and Etifoxine in people with Multiple Sclerosis, run by Imperial College London at 1 site in United Kingdom.
Trial summary
In multiple sclerosis (MS) cells of the immune system attack the brain causing tissue damage. In secondary progressive MS (SPMS) these repeated immune attacks have stopped but despite this new damage continues to appear. Read more about this study
- Who is it for?
- Ages 35 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- XBD173 and Etifoxine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 44 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 1 Jan 2018to 31 Jan 2025
- 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 35 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
- Aged 35-65 years old
- A female subject is eligible to participate if she is a) of non-childbearing potential, defined as pre-menopausal females with a documented tubal ligation or hysterectomy, or postmenopausal defined as 12 months of spontaneous amenorrhea or b) of childbearing potential but not pregnant (as determined by urinary pregnancy test on screening and on each study day) and willing to use one of the contraception methods listed below
- Male subject must agree to use one of the contraception methods listed above.
- Willing to abstain from alcohol for the duration of dosing.
- Expanded Disability Status Scale (EDSS) >3.5 <6.5 (SPMS patients only)
Who cannot join
- History of active neurological disease other than migraine or MS
- Clinically meaningful abnormalities in routine bloods including:
- eGFR < 60ml/min
- Elevation of liver enzymes/bilirubin
- Prolonged prothrombin time
- Thrombocytopenia
Show all 24Show fewer
- Use of the following medications or therapies:
- Immunosuppressive or immunomodulatory drugs within the last 6 months
- Alemtuzumab or haematopeotic stem cell therapy
- Central nervous system depressants (including opioid analgesics, barbiturates, sleeping pills, antihistamines, antipsychotics)
- P450 CY3A4 inducers or inhibitors
- oral contraceptives
- oral anticoagulants or antiplatelet agents other than low dose aspirin
- levothyroxine
- Currently breastfeeding
- Any clinical significant medical conditions that in the opinion of the investigator would compromise subjects' safety or compliance with study procedures.
- History of any clinical condition which in the opinion of the principal investigator would compromise the scientific integrity of the study, such as some chronic systemic diseases affecting blood, liver or kidneys or endocrine system
- Unwillingness or inability to follow the procedures outlined in the protocol
- Subject is mentally or legally incapacitated
- Contraindication to XBD173 use:
- Hypersensitivity to the active substance or to any of the excipients
- Contraindication to etifoxine use:
- Myasthenia gravis
- syndromes of glucose and galactose malabsorption or lactose deficiency
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site, 1 recruiting
- Recruiting
Imperial College Healthcare NHS Trust
London, England, W12 0NN
Richard Nicholas, PhD, r.nicholas@imperial.ac.uk
About this study
Official title: An Experimental Medicine Study to Validate the 18 kiloDalton Translocator Protein (TSPO) as a Novel Neuroimmunodulatory Target in Multiple Sclerosis
In multiple sclerosis (MS) cells of the immune system attack the brain causing tissue damage. In secondary progressive MS (SPMS) these repeated immune attacks have stopped but despite this new damage continues to appear. TSPO is a protein found in the brain and cells of the immune system, whose levels increase during MS. The investigators would like to know whether drugs that bind TSPO could dampen the immune responses in patients with SPMS. The investigators will be testing two drugs that affect TSPO; etifoxine and XBD173. Subjects with SPMS will be recruited from neurology clinics at hospitals associated with Imperial College Healthcare NHS Trust. Healthy volunteers will also be recruited in order to provide a comparison to these patients. The volunteers recruited will be invited to the clinical research facility (CRF) at Hammersmith Hospital. The volunteers will take one of the two drugs every day for 7 days. The researchers will perform blood tests before the first dose and after the last dose to investigate the effects of the drugs, including the expression of genes and immune cell activity. This will allow the researchers to explore which of the two drugs produces the greatest changes in the amount of TSPO in the blood in MS patients relative to healthy controls.
Read the detailed description
The 18 kiloDalton Translocator Protein (TSPO) is a mitochondrial protein highly expressed in myeloid cells. While the full range of its functions are unknown, preclinical and in vitro studies provide suggestive evidence that TSPO ligands alter TSPO protein function to bias monocytes/macrophages and microglia towards reparative phenotypes. XBD173 and etifoxine are two TSPO ligands and represent two distinct chemotypes. Etifoxine is a benzoxaine, licenced in France (although not the UK) for the treatment of anxiety. XBD173 (Emapunil) is a phenylpurine that has recently been investigated for the treatment of anxiety, but is not licensed.
The aim of this experimental medicine study is to test the hypothesis in humans that functional changes effected by TSPO can induce pro-inflammatory monocytes/macrophages and microglia to adopt a reparative phenotype. People with multiple sclerosis (MS) will be enrolled in this study because monocytes from MS patients have a chronic pro-inflammatory phenotype. Healthy volunteers (HVs) will also be enrolled to determine whether TSPO mediated effects are immune state dependant.
The primary objective of this study is to determine the effects of TSPO ligand binding on monocyte/macrophage phenotype in humans.
The secondary objectives are:
a To characterise immunological responses in blood plasma and in circulating immune cell subsets of healthy volunteers and people with SPMS after TSPO functional changes induced by challenge ligand binding.
b To explore the potential dependence of these pharmacodynamic responses on variation at rs6971 (a common polymorphism influencing ligand binding affinities in the TSPO protein) in the TSPO gene.
- Conditions
- Multiple Sclerosis
- Being tested
- XBD173, Etifoxine
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
XBD173Drug
7 days treatment
EtifoxineDrug
7 days treatment
| Study group | Role | What they receive |
|---|---|---|
| Etifoxine then XBD173 | Experimental | Not described Receives: Drug: XBD173; Drug: Etifoxine |
| XBD173 then Etifoxine | Experimental | Not described Receives: Drug: XBD173; Drug: Etifoxine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Monocyte phenotye - Tissue necrosis factor-α
Plasma cytokine concentrations
Measured: 7 days
Monocyte phenotye - Interferon-γ
Plasma cytokine concentrations
Measured: 7 days
Monocyte phenotype - Interleukins- 1β
Plasma cytokine concentrations
Measured: 7 days
Monocyte phenotype - Interleukins- 16
Plasma cytokine concentrations
Measured: 7 days
Monocyte phenotype - Interleukins- 17
Plasma cytokine concentrations
Measured: 7 days
Monocyte phenotype - Interleukins- 23
Plasma cytokine concentrations
Measured: 7 days
Immunomodulatory factor -Transforming growth factor-β
Transforming growth factor-β
Measured: 7 days
Immunomodulatory factor - Interleukins -4
Interleukins -4
Measured: 7 days
Immunomodulatory factor - Interleukins - 10
Interleukins - 10
Measured: 7 days
Relative proportions of WBC subsets
Flow
Measured: 7 days
Secondary outcomes (2)
Monocyte phenotype - 'omic analyses
Genome, proteome, metabolome
Measured: 7 days
Neurofilament
Plasma levels of neurofilament
Measured: 7 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Feb 2019
- Study start1 Jan 2018
- Primary completion31 Jan 2025 (estimated)
- Study completion31 Jan 2025 (estimated)
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.
- More trials run by Imperial College LondonThe 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
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 44 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Paul Matthews, PhD, Study chair, Imperial College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03850301
- Sponsor's protocol ID
- 17HH3814
- Acronym
- TSPO
- Status last verified
- Oct 2024
- First submitted
- 12 Feb 2019
- Last updated
- 15 Oct 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 15 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Experimental Medicine Study to Validate the 18 kiloDalton Translocator Protein (TSPO) as a Novel Neuroimmunodulatory Target in Multiple Sclerosis
- ClinicalTrials.gov ID
- NCT03850301
- Acronym / sponsor ID
- TSPO / 17HH3814
- Conditions
- Multiple Sclerosis
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 44 participants (estimated)
- Lead sponsor
- Imperial College LondonUniversity, hospital or other
- Study start
- 1 Jan 2018 (actual)
- Primary completion
- 31 Jan 2025 (estimated)
- Study completion
- 31 Jan 2025 (estimated)
- First posted
- 21 Feb 2019 (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.
In multiple sclerosis (MS) cells of the immune system attack the brain causing tissue damage. In secondary progressive MS (SPMS) these repeated immune attacks have stopped but despite this new damage continues to appear. TSPO is a protein found in the brain and cells of the immune system, whose levels increase during MS. The investigators would like to know whether drugs that bind TSPO could dampen the immune responses in patients with SPMS. The investigators will be testing two drugs that affect TSPO; etifoxine and XBD173. Subjects with SPMS will be recruited from neurology clinics at hospitals associated with Imperial College Healthcare NHS Trust. Healthy volunteers will also be recruited in order to provide a comparison to these patients. The volunteers recruited will be invited to the clinical research facility (CRF) at Hammersmith Hospital. The volunteers will take one of the two drugs every day for 7 days. The researchers will perform blood tests before the first dose and after the last dose to investigate the effects of the drugs, including the expression of genes and immune cell activity. This will allow the researchers to explore which of the two drugs produces the greatest changes in the amount of TSPO in the blood in MS patients relative to healthy controls.
Detailed description
The 18 kiloDalton Translocator Protein (TSPO) is a mitochondrial protein highly expressed in myeloid cells. While the full range of its functions are unknown, preclinical and in vitro studies provide suggestive evidence that TSPO ligands alter TSPO protein function to bias monocytes/macrophages and microglia towards reparative phenotypes. XBD173 and etifoxine are two TSPO ligands and represent two distinct chemotypes. Etifoxine is a benzoxaine, licenced in France (although not the UK) for the treatment of anxiety. XBD173 (Emapunil) is a phenylpurine that has recently been investigated for the treatment of anxiety, but is not licensed.
The aim of this experimental medicine study is to test the hypothesis in humans that functional changes effected by TSPO can induce pro-inflammatory monocytes/macrophages and microglia to adopt a reparative phenotype. People with multiple sclerosis (MS) will be enrolled in this study because monocytes from MS patients have a chronic pro-inflammatory phenotype. Healthy volunteers (HVs) will also be enrolled to determine whether TSPO mediated effects are immune state dependant.
The primary objective of this study is to determine the effects of TSPO ligand binding on monocyte/macrophage phenotype in humans.
The secondary objectives are:
a To characterise immunological responses in blood plasma and in circulating immune cell subsets of healthy volunteers and people with SPMS after TSPO functional changes induced by challenge ligand binding.
b To explore the potential dependence of these pharmacodynamic responses on variation at rs6971 (a common polymorphism influencing ligand binding affinities in the TSPO protein) in the TSPO gene.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Etifoxine then XBD173 | Experimental | Drug: XBD173, Drug: Etifoxine |
| XBD173 then Etifoxine | Experimental | Drug: XBD173, Drug: Etifoxine |
Who may qualify
- Ages
- 35 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
- Aged 35-65 years old
- A female subject is eligible to participate if she is a) of non-childbearing potential, defined as pre-menopausal females with a documented tubal ligation or hysterectomy, or postmenopausal defined as 12 months of spontaneous amenorrhea or b) of childbearing potential but not pregnant (as determined by urinary pregnancy test on screening and on each study day) and willing to use one of the contraception methods listed below
- Male subject must agree to use one of the contraception methods listed above.
- Willing to abstain from alcohol for the duration of dosing.
Key exclusion criteria (24 listed)
- History of active neurological disease other than migraine or MS
- Clinically meaningful abnormalities in routine bloods including:
- Use of the following medications or therapies:
- Currently breastfeeding
- Any clinical significant medical conditions that in the opinion of the investigator would compromise subjects' safety or compliance with study procedures.
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 |
|---|---|---|
| XBD1737 days treatment | Drug | Etifoxine then XBD173, XBD173 then Etifoxine |
| Etifoxine7 days treatment | Drug | Etifoxine then XBD173, XBD173 then Etifoxine |
Primary outcome
Monocyte phenotye - Tissue necrosis factor-α
Time frame: 7 days
Plasma cytokine concentrations
Monocyte phenotye - Interferon-γ
Time frame: 7 days
Plasma cytokine concentrations
Monocyte phenotype - Interleukins- 1β
Time frame: 7 days
Plasma cytokine concentrations
Monocyte phenotype - Interleukins- 16
Time frame: 7 days
Plasma cytokine concentrations
Monocyte phenotype - Interleukins- 17
Time frame: 7 days
Plasma cytokine concentrations
Monocyte phenotype - Interleukins- 23
Time frame: 7 days
Plasma cytokine concentrations
Immunomodulatory factor -Transforming growth factor-β
Time frame: 7 days
Transforming growth factor-β
Immunomodulatory factor - Interleukins -4
Time frame: 7 days
Interleukins -4
Immunomodulatory factor - Interleukins - 10
Time frame: 7 days
Interleukins - 10
Relative proportions of WBC subsets
Time frame: 7 days
Flow
2 secondary outcomes
Monocyte phenotype - 'omic analyses
Time frame: 7 days
Neurofilament
Time frame: 7 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Oct 2024.
- Individual participant dataSharing planned: Undecided
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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.
Paul Matthews, PhD study chair
Imperial College London
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing XBD173 and Etifoxine in people with Multiple Sclerosis, run by Imperial College London at 1 site in United Kingdom.
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 6 inclusion and 24 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 15 Oct 2024. 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 United Kingdom. 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 David Owen, PhD (07801140800, d.owen@imperial.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Monocyte phenotye - Tissue necrosis factor-α (time frame: 7 days). The study lists 10 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 15 Oct 2024.