Alzheimer s DiseasePhase 2NCT07191821
TSPO Modulation in AD
A Phase 2 study testing XBD173 in people with Alzheimer s Disease, run by Imperial College London at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 90 yearsHealthy volunteers can take part
- Conditions the study is for
- Alzheimer s Disease
- What is being tested?
- XBD173
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 51 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 8 Aug 2025to 1 Jun 2027
- Phase
- Phase 2
- 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 18 to 90 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Show all 14Show fewer
- Mild - moderate cognitive impairment (MMSE = 20-27 )
- AD biomarker positive MCI patients
- 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
Who cannot join
- 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)
Show all 17Show fewer
- 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
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Modulation of Endothelial Function in Alzheimer's Disease by 18kDa Translocator Protein
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)).
Read more
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.
- Conditions
- Alzheimer s Disease
- Being tested
- XBD173
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
XBD173Drug
Small molecule experimental medication binding to mitochondrial protein TSPO
| Study group | Role | What they receive |
|---|---|---|
| XBD173 followed by Placebo | Other | 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 Receives: Drug: XBD173 |
| Placebo followed by XBD173 | Other | 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 Receives: Drug: XBD173 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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?
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)).
Measured: From baseline to 4 week follow-up after taking medication/placebo
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Sep 2025
- Study start8 Aug 2025
- Primary completion1 Mar 2027 (estimated)
- Study completion1 Jun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alzheimer s 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 2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 51 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- David Owen, Principal investigator, Imperial College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07191821
- Sponsor's protocol ID
- 23/LO/0080
- Status last verified
- Sep 2025
- First submitted
- 17 Sep 2025
- Last updated
- 1 Oct 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Modulation of Endothelial Function in Alzheimer's Disease by 18kDa Translocator Protein
- ClinicalTrials.gov ID
- NCT07191821
- Acronym / sponsor ID
- 23/LO/0080
- Conditions
- Alzheimer s Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Enrolling by invitation
- Enrolment
- 51 participants (estimated)
- Lead sponsor
- Imperial College LondonUniversity, hospital or other
- Study start
- 8 Aug 2025 (actual)
- Primary completion
- 1 Mar 2027 (estimated)
- Study completion
- 1 Jun 2027 (estimated)
- First posted
- 25 Sep 2025 (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.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| XBD173 followed by Placebo | Other | Drug: XBD173Participants 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 | Other | Drug: XBD173Participants 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 |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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
Key exclusion criteria (17 listed)
- 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)
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 |
|---|---|---|
| XBD173Small molecule experimental medication binding to mitochondrial protein TSPO | Drug | Placebo followed by XBD173, XBD173 followed by Placebo |
Primary outcome
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?
Time frame: 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)).
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 1 Oct 2025.
- Individual participant dataSharing planned: No
Related trials for Alzheimer s Disease
RecruitingObservational study
Speech and Language Interventions for Italian People With PPA
Primary Progressive Aphasia(PPA)
RecruitingPhase 1
PET Imaging of Phosphodiesterase-4 (PDE4) in Volunteers With Alzheimer Disease (AD) or Mild Cognitive Impairment (MCI)
Alzheimer s Disease, Mild Cognitive Impairment
Active, not recruitingPhase 1/2
VY7523-102: Randomized, Placebo-Controlled, Double-Blind, Multiple Ascending Dose Study in Participants With Early Alzheimer's Disease
Alzheimer's Disease (AD)
Not yet recruitingObservational study
MENA/Levant Epidemiological, Registry of Immunological & Clinical Traits (MERIT)
Antiphospholipid (aPL)-Positive, Rheumatic Arthritis
Recruiting
CommunityRx-Dementia + Peer Navigation (CRxDpeer)
Alzheimer s Disease, Dementia
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.
David Owen principal investigator
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 Phase 2 study testing XBD173 in people with Alzheimer s 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 14 inclusion and 17 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: enrolling by invitation, as of the sponsor's last update on 1 Oct 2025. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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? (time frame: From baseline to 4 week follow-up after taking medication/placebo). 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 1 Oct 2025.