Validation of the 18 kiloDalton Translocator Protein (TSPO) as a Novel Neuroimmunodulatory Target
TSPO
An Experimental Medicine Study to Validate the 18 kiloDalton Translocator Protein (TSPO) as a Novel Neuroimmunodulatory Target in Multiple Sclerosis
1 other identifier
interventional
44
1 country
1
Brief 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. 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for not_applicable multiple-sclerosis
Started Jan 2018
Longer than P75 for not_applicable multiple-sclerosis
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
January 1, 2018
CompletedFirst Submitted
Initial submission to the registry
February 12, 2019
CompletedFirst Posted
Study publicly available on registry
February 21, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 31, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
January 31, 2025
CompletedOctober 15, 2024
October 1, 2024
7.1 years
February 12, 2019
October 14, 2024
Conditions
Outcome Measures
Primary Outcomes (10)
Monocyte phenotye - Tissue necrosis factor-α
Plasma cytokine concentrations
7 days
Monocyte phenotye - Interferon-γ
Plasma cytokine concentrations
7 days
Monocyte phenotype - Interleukins- 1β
Plasma cytokine concentrations
7 days
Monocyte phenotype - Interleukins- 16
Plasma cytokine concentrations
7 days
Monocyte phenotype - Interleukins- 17
Plasma cytokine concentrations
7 days
Monocyte phenotype - Interleukins- 23
Plasma cytokine concentrations
7 days
Immunomodulatory factor -Transforming growth factor-β
Transforming growth factor-β
7 days
Immunomodulatory factor - Interleukins -4
Interleukins -4
7 days
Immunomodulatory factor - Interleukins - 10
Interleukins - 10
7 days
Relative proportions of WBC subsets
Flow
7 days
Secondary Outcomes (2)
Monocyte phenotype - 'omic analyses
7 days
Neurofilament
7 days
Study Arms (2)
Etifoxine then XBD173
EXPERIMENTALXBD173 then Etifoxine
EXPERIMENTALInterventions
Eligibility Criteria
You may qualify if:
- 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)
You may not qualify if:
- 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
- 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
- +9 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Imperial College Healthcare NHS Trust
London, England, W12 0NN, United Kingdom
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
Paul Matthews, PhD
Imperial College London
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- SINGLE
- Who Masked
- OUTCOMES ASSESSOR
- Masking Details
- The people who undertake the analysis of the blood test will be blind about whether the blood sample came from an MS patient or a healthy volunteer.
- Purpose
- OTHER
- Intervention Model
- CROSSOVER
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 12, 2019
First Posted
February 21, 2019
Study Start
January 1, 2018
Primary Completion
January 31, 2025
Study Completion
January 31, 2025
Last Updated
October 15, 2024
Record last verified: 2024-10