TSPO Modulation in AD

Not Applicable

• Conditions: Alzheimer s Disease
• Interventions: Drug: XBD173

• Registration Number: NCT07191821
• Lead Sponsor: Imperial College London

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. The main questions it aims to answer are:

Does pharmacological modulation of TSPO (with XBD173, 90mg twice daily, orally, for 28 days) improve neurovascular coupling (NVC) in people with AD compared to placebo? NVC will be defined as the change in hippocampal cerebral blood flow (CBF) that follows a memory task (ΔCBF(h)).

Does pharmacological modulation of TSPO (with XBD173, 90mg twice daily, orally, for 28 days): Increase cerebral blood flow (CBF); Reduce blood brain barrier leak (rate and volume) determined by Gd enhanced DCE-MRI; Increase plasma Amyloid 40/42; Reduce soluble markers of endothelial cell activation(sVCAM1, sICAM1, PECAM1, E-selectin, vWF); Improve markers of peripheral endothelial cell function; Cerebrovascular reactivity in response to CO2 inhalation

The first six participants will undergo a dose escalation phase. The first 3 participants will receive XBD173 (90mg, once daily, 28 days) and the subsequent 3 participants will receive XBD173 (90mg, twice daily, 28 days). This phase will be open label. Participants will have 1 safety visits and 2 assessment visits. Each Assessment visit will involve clinical tests, a blood test and an MRI scan. Participants in the Randomisation phase participants will be given either 90mg of XBD173, twice daily or a placebo (dummy drug) for 4 weeks, have 2 safety visits and 4 assessment visits. Each Assessment visit will involve clinical tests, a blood test and an MRI scan. Healthy Volunteers will be recruited and undergo a screening visit and MRI scan.

Detailed Description

Not available

Study Timeline

• Study Start: 2025-08-08
• Status Verified: 2025-09
• Study First Submitted: 2025-09-17
• Study First Submitted QC: 2025-09-17
• Study First Posted: 2025-09-25
• Last Update Submitted: 2025-09-26
• Last Update Posted: 2025-10-01
• Primary Completion: 2027-03-01
• Study Completion: 2027-06-01

Recruitment & Eligibility

• Status: ENROLLING_BY_INVITATION
• Sex: All
• Target Recruitment: 51

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
XBD173 followed by Placebo	XBD173	Participants will receive experimental medication XBD173 twice a day for 4 weeks followed by a 6 week washout before beginning a 4 week course of placebo twice a day. Both arms are double blinded
Placebo followed by XBD173	XBD173	Participants will receive placebo twice a day for 4 weeks followed by a 6 week washout before beginning a 4 week course of experimental medication XBD173 twice a day. Both arms are double blinded

Primary Outcome Measures

Name	Time	Method
Does pharmacological modulation of TSPO (with XBD173, 90mg twice daily, orally, for 28 days) improve neurovascular coupling (NVC) in people with AD compared to placebo?	From baseline to 4 week follow-up after taking medication/placebo	Does pharmacological modulation of TSPO (with XBD173, 90mg twice daily, orally, for 28 days) improve neurovascular coupling (NVC) in people with AD compared to placebo? NVC will be defined as the change in hippocampal cerebral blood flow (CBF) that follows a memory task (ΔCBF(h)).

Trial Locations

Locations (1)

NIHR Imperial CRF; 🇬🇧 London, United Kingdom