Cerebral Small Vessel DiseaseNCT06643013
Targeting 18kDa Translocator Protein (TSPO) to Improve Brain Endothelial Cell Function in Cerebral Small Vessel Disease
A study testing XBD173 in people with Cerebral Small Vessel Disease, run by Imperial College London at 1 site in United Kingdom.
Trial summary
In healthy people, blood flow to particular areas in the brain increases when the area becomes more active. This ensures that the brain gets enough blood at the right place and time. Read more about this study
- Who is it for?
- Ages 60 to 90 yearsHealthy volunteers can take part
- Conditions the study is for
- Cerebral Small Vessel Disease
- What is being tested?
- XBD173
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 106 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Oct 2024to Apr 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 60 to 90 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Aged 60-90 years inclusive Male or postmenopausal female
- Men are eligible to participate if they are willing to use the contraception methods listed in the PIS, during treatment and for 90 days after the last dose of treatment Able to provide written informed consent prior to any study-mandated procedures AA genotype at rs6971 (TSPO) locus Imaging-based diagnosis of cSVD (Fazekas score of at least 2 for periventricular and 2 for deep white matter) Mild cognitive impairment (MoCA 18-30) Willing to be genotyped at TSPO and ApoE loci
- Aged 60-90 years inclusive Male or female Able to provide written informed consent prior to any study-mandated procedures.
- Willing to be genotyped at TSPO and ApoE loci
Who cannot join
- History of clinical stroke History of frequent migraines Known Alzheimer's disease, lewy body disease or evidence of non-vascular neurological diseases Conditions affecting safe engagement in the intervention. Conditions preventing completion of study procedures, e.g. severe loss of vision or hearing Clinically-significant renal disease (eGFR <30 ml/min per 1.73m2) Clinically-significant elevation of serum transaminases or known clinically significant liver disease Contraindications to MRI scanning or exposure to gadolinium-based contrast agents Newly commenced (within 2 months of study start) statins, antihypertensives or antiplatelet treatments Severe respiratory disease with chronic hypoxia (sats <92%), known CO2 retention or need for home oxygen therapy.
- Use of the following medications or therapies:
- Severe and moderate P450 CY3A4 inhibitors: Boceprevir, Clarithromycin, Cobicistat, Idelalisib, Itraconazole, Ketoconazole, Nelfinavir, Ritonavir, Saquinavir, Telaprevir, Telithromycin, Voriconazole, Aprepitant, Conivaptan, Crizotinib, Diltiazem, Dronedarone, Erythromycin, Fluconazole, Imatinib, Isavuconazole, Nefazodone, Netupitant, Nilotinib, Posaconazole, Tofisopam, Verapamil, Delavirdine.
- Severe and moderate P450 CY3A4 inducers: Carbamazepine, Enzalutamide, Fosphenytoin, Mitotane, Phenytoin, Rifampicin, Bosentan, Efavirenz, St John's wort, Barbiturates, Nevirapine, Primidone, Rifabutin, Rifapentine.
- Oral contraceptives
- Levothyroxine
- Contraindications to MRI scanning or exposure to gadolinium-based contrast agents Pregnant women of childbearing potential Clinically significant renal disease (eGFR <30 ml/min per 1.73m2) Severe respiratory disease with chronic hypoxia (sats <92%), known CO2 retention or need for home oxygen therapy.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United Kingdom1 site, 1 recruiting
- Recruiting
Imperial Clinical Research Facility
London
David Owen, PhD, +442033136195, d.owen@imperial.ac.uk
About this study
In healthy people, blood flow to particular areas in the brain increases when the area becomes more active. This ensures that the brain gets enough blood at the right place and time. In people with cerebral small vessel disease (cSVD), this process is disrupted, and the increased blood flow in response to activity is decreased or absent. Damage to the endothelial cells, that form the inner lining of blood vessels, is a key pathological process in cSVD. The aim of this study is to find out whether endothelial cell function and blood flow in cSVD can be improved by altering the function of a protein called TSPO. We will do this by using a drug called XBD173, which binds to TSPO.
This is a double-blind, randomised, crossover study. cSVD patients will be recruited from memory clinics at Imperial College Healthcare NHS Trust. Participants will be invited to the clinical research facility (CRF) at Hammersmith Hospital and randomised to receive XBD173 or matched placebo, twice daily, for 4 weeks. After a 6-week washout, they will be switched to receive the other intervention. The study visits will involve MRI scans and blood tests to assess endothelial cell function.
Healthy volunteers will also be recruited for image optimisation and control data. They will attend for a single MRI scan and not receive XBD173.
- Conditions
- Cerebral Small Vessel Disease
- Being tested
- XBD173
- Medical subject headings
- Cerebral Small Vessel Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
XBD173Drug
4 weeks treatment
| Study group | Role | What they receive |
|---|---|---|
| XBD173 then Placebo | Experimental | Not described Receives: Drug: XBD173 |
| Placebo then XBD173 | Experimental | Not described Receives: Drug: XBD173 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Neurovascular coupling
Change in primary visual cortex cerebral blood flow following an alertness task
Measured: 4 weeks
Secondary outcomes (2)
Neurovascular coupling
Change in cerebral blood flow in a ROI generated by a group average mask of regions known to become activated in the frontal and temporal lobes
Measured: 4 weeks
Blood-brain barrier leak
BBB leak (rate and volume) determined by gadolinium-enhanced DCE-MRI
Measured: 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Oct 2024
- Study startOct 2024 (estimated)
- Primary completionApr 2028 (estimated)
- Study completionApr 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cerebral Small Vessel DiseaseStudies 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 106 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
- NCT06643013
- Sponsor's protocol ID
- 24HH8841
- Status last verified
- Oct 2024
- First submitted
- 14 Oct 2024
- Last updated
- 15 Oct 2024
- Results posted
- No
- Data monitoring committee
- Yes
- 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
- Targeting 18kDa Translocator Protein (TSPO) to Improve Brain Endothelial Cell Function in Cerebral Small Vessel Disease
- ClinicalTrials.gov ID
- NCT06643013
- Acronym / sponsor ID
- 24HH8841
- Conditions
- Cerebral Small Vessel Disease
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 106 participants (estimated)
- Lead sponsor
- Imperial College LondonUniversity, hospital or other
- Study start
- Oct 2024 (estimated)
- Primary completion
- Apr 2028 (estimated)
- Study completion
- Apr 2028 (estimated)
- First posted
- 15 Oct 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.
In healthy people, blood flow to particular areas in the brain increases when the area becomes more active. This ensures that the brain gets enough blood at the right place and time. In people with cerebral small vessel disease (cSVD), this process is disrupted, and the increased blood flow in response to activity is decreased or absent. Damage to the endothelial cells, that form the inner lining of blood vessels, is a key pathological process in cSVD. The aim of this study is to find out whether endothelial cell function and blood flow in cSVD can be improved by altering the function of a protein called TSPO. We will do this by using a drug called XBD173, which binds to TSPO.
This is a double-blind, randomised, crossover study. cSVD patients will be recruited from memory clinics at Imperial College Healthcare NHS Trust. Participants will be invited to the clinical research facility (CRF) at Hammersmith Hospital and randomised to receive XBD173 or matched placebo, twice daily, for 4 weeks. After a 6-week washout, they will be switched to receive the other intervention. The study visits will involve MRI scans and blood tests to assess endothelial cell function.
Healthy volunteers will also be recruited for image optimisation and control data. They will attend for a single MRI scan and not receive XBD173.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| XBD173 then Placebo | Experimental | Drug: XBD173 |
| Placebo then XBD173 | Experimental | Drug: XBD173 |
Who may qualify
- Ages
- 60 to 90 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Aged 60-90 years inclusive Male or postmenopausal female
- Men are eligible to participate if they are willing to use the contraception methods listed in the PIS, during treatment and for 90 days after the last dose of treatment Able to provide written informed consent prior to any study-mandated procedures AA genotype at rs6971 (TSPO) locus Imaging-based diagnosis of cSVD (Fazekas score of at least 2 for periventricular and 2 for deep white matter) Mild cognitive impairment (MoCA 18-30) Willing to be genotyped at TSPO and ApoE loci
- Aged 60-90 years inclusive Male or female Able to provide written informed consent prior to any study-mandated procedures.
- Willing to be genotyped at TSPO and ApoE loci
Key exclusion criteria (7 listed)
- History of clinical stroke History of frequent migraines Known Alzheimer's disease, lewy body disease or evidence of non-vascular neurological diseases Conditions affecting safe engagement in the intervention. Conditions preventing completion of study procedures, e.g. severe loss of vision or hearing Clinically-significant renal disease (eGFR <30 ml/min per 1.73m2) Clinically-significant elevation of serum transaminases or known clinically significant liver disease Contraindications to MRI scanning or exposure to gadolinium-based contrast agents Newly commenced (within 2 months of study start) statins, antihypertensives or antiplatelet treatments Severe respiratory disease with chronic hypoxia (sats <92%), known CO2 retention or need for home oxygen therapy.
- Severe and moderate P450 CY3A4 inhibitors: Boceprevir, Clarithromycin, Cobicistat, Idelalisib, Itraconazole, Ketoconazole, Nelfinavir, Ritonavir, Saquinavir, Telaprevir, Telithromycin, Voriconazole, Aprepitant, Conivaptan, Crizotinib, Diltiazem, Dronedarone, Erythromycin, Fluconazole, Imatinib, Isavuconazole, Nefazodone, Netupitant, Nilotinib, Posaconazole, Tofisopam, Verapamil, Delavirdine.
- Severe and moderate P450 CY3A4 inducers: Carbamazepine, Enzalutamide, Fosphenytoin, Mitotane, Phenytoin, Rifampicin, Bosentan, Efavirenz, St John's wort, Barbiturates, Nevirapine, Primidone, Rifabutin, Rifapentine.
- Oral contraceptives
- Levothyroxine
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 |
|---|---|---|
| XBD1734 weeks treatment | Drug | Placebo then XBD173, XBD173 then Placebo |
Primary outcome
Neurovascular coupling
Time frame: 4 weeks
Change in primary visual cortex cerebral blood flow following an alertness task
2 secondary outcomes
Neurovascular coupling
Time frame: 4 weeks
Blood-brain barrier leak
Time frame: 4 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
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.
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 in people with Cerebral Small Vessel Disease, 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 4 inclusion and 7 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: looking for participants now, 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact David Owen, PhD (+442033136195, 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?
Neurovascular coupling (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 15 Oct 2024.