Improving brain blood flow in patients with cerebral small vessel disease

Targeting 18kDa Translocator Protein (TSPO) to Improve Brain Endothelial Cell Function in Cerebral Small Vessel Disease

This study is testing if a new drug can improve blood flow in the brains of people with cerebral small vessel disease.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 106 (estimated)
• Ages: 60 Years to 90 Years
• Sex: All
• Sponsor: Imperial College London (Academic / other)
• Drugs / interventions: Crizotinib, Imatinib, Nilotinib
• Locations: 1 site (London)
• Trial ID: NCT06643013 on ClinicalTrials.gov

What this trial studies

This study aims to enhance endothelial cell function and blood flow in patients with cerebral small vessel disease (cSVD) by targeting a protein called TSPO using a drug named XBD173. It is a double-blind, randomized, crossover study where participants will receive either the drug or a placebo twice daily for four weeks. Patients will be recruited from memory clinics at Imperial College Healthcare NHS Trust and will undergo genotyping to assess their eligibility. The study will evaluate the effects of the intervention on blood flow response in the brain during activity.

Who should consider this trial

Good fit: Ideal candidates are individuals aged 60-90 with imaging-confirmed cerebral small vessel disease and mild cognitive impairment.

Not a fit: Patients with a history of clinical stroke or other significant neurological diseases may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved blood flow and cognitive function in patients with cerebral small vessel disease.

How similar studies have performed: While this approach is novel, similar studies targeting endothelial function in vascular diseases have shown promise.

Eligibility criteria

Inclusion Criteria:

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

Inclusion Criteria (Healthy Volunteers):

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

Exclusion Criteria:

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

Exclusion Criteria (Healthy Volunteers):

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.

Where this trial is running

London

• Imperial Clinical Research Facility — London, United Kingdom (Recruiting)

Study contacts

• Study coordinator: David Owen, PhD

Conditions Cerebral Small Vessel Disease