Status:

ENROLLING_BY_INVITATION

TSPO Modulation in AD

Lead Sponsor:

Imperial College London

Conditions:

Alzheimer s Disease

Eligibility:

All Genders

18-90 years

Phase:

PHASE2

Brief Summary

The aim of this study is to determine whether pharmacological modulation of TSPO (with XBD173, 90mg twice daily, orally, for 28 days) improves neurovascular coupling (NVC) in AD relative to placebo. T...

Eligibility Criteria

Inclusion

  • Inclusion criteria for AD:
  • Subjects aged between 60-90 years old
  • Male or postmenopausal female
  • Fertile 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
  • Clinical diagnosis of AD by dementia specialist, fulfilling NIA-AA criteria
  • Mild - moderate cognitive impairment (MMSE = 20-27 )
  • AD biomarker positive MCI patients
  • Inclusion criteria for HV:
  • Subjects aged 18 years or older
  • Male or Female
  • Female subjects of childbearing potential must be willing to have a pregnancy test before scanning
  • Able to provide written informed consent prior to any study-mandated procedures
  • Subjects willing to have blood samples collected for genotyping (ApoE and TSPO rs6971)
  • AD biomarker positive
  • Exclusion criteria for AD:
  • History of migraine (with attack frequency greater than 1 per month)
  • Clinical history of suggestive of dementia with Lewy Bodies such as REM Sleep Behaviour Disorder
  • 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 \<60 ml/min per 1.73m2)
  • Clinically significant liver disease (abnormal serum transaminases)
  • Contraindications to MRI scanning or exposure to gadolinium-based contrast agents
  • Change of medications approved for AD (eg. Galantamine, rivastigmine, and donepezil) or antihypertensives within the last 28 days or planned during the timeframe of the study
  • 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, Voriconazoleb, Aprepitant, Conivaptan, Crizotinib, Diltiazem, Dronedarone, Erythromycin, Fluconazole, Imatinib, Isavuconazole, Nefazodone, Netupitant, Nilotinib, Posaconazolee, 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
  • Exclusion criteria for HV
  • Contraindications to MRI scanning or exposure to gadolinium-based contrast agents
  • Pregnancy in WOCBP
  • eGFR\<60 ml/min per 1.73 m2
  • Severe respiratory disease with chronic hypoxia (sats \<92%), known CO2 retention or need for home oxygen therapy

Exclusion

    Key Trial Info

    Start Date :

    August 8 2025

    Trial Type :

    INTERVENTIONAL

    Allocation :

    ESTIMATED

    End Date :

    June 1 2027

    Estimated Enrollment :

    51 Patients enrolled

    Trial Details

    Trial ID

    NCT07191821

    Start Date

    August 8 2025

    End Date

    June 1 2027

    Last Update

    October 1 2025

    Active Locations (1)

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    NIHR Imperial CRF

    London, United Kingdom, W12 0HS