Role of a Mitochondrial Receptor in Blood Sugar Regulation (G-TSPO)

An Experimental Medicine Study to Investigate the Role of the 18 kiloDalton Translocator Protein in Glucose Metabolism

The goal of this clinical trial is to learn whether a single dose of XBD173, a medicine that binds to a protein called the 18 kiloDalton Translocator Protein (TSPO), affects how the body processes glucose in healthy volunteers aged 18 to 75 years.

The main questions it aims to answer are:

• Does a single dose of XBD173 change fasting blood glucose levels compared with placebo?
• Does a single dose of XBD173 change blood glucose levels after participants drink a glucose solution compared with placebo?

Researchers will compare XBD173 with a placebo, which does not contain the active medicine, to see whether activating TSPO affects glucose metabolism in the fasting state and after a glucose drink.

Participants will:

• Attend a screening visit to confirm eligibility, including a medical history, physical examination and blood tests.
• Attend four study visits after fasting overnight: two visits involving a glucose drink and two visits without a glucose drink.
• Receive a single oral dose of XBD173 at some visits and placebo at other visits. The order will be randomised, and neither participants nor the study team conducting the assessments will know which treatment is given during each visit.
• Have repeated blood samples taken through a cannula to measure glucose, insulin and other markers related to metabolism and inflammation.
• Have resting energy use measured by breathing under a transparent canopy connected to a standard metabolic measurement device.
• Have blood pressure, heart rate, height and weight measured.
• Undergo measurement of blood vessel function using a cuff.

Study Overview

• Status: Recruiting
• Conditions: Heathly Volunteers
• Intervention / Treatment: Drug: XBD173; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: David R Owen; Phone Number: +44 07801140800; Email: d.owen@imperial.ac.uk

Study Locations

• United Kingdom
  • London, United Kingdom, W120NN
    • Recruiting
    • NIHR Trust Imperial Clinical Research Facility
    • Contact: Yucen Wu; Phone Number: +44 020 3313 8082; Email: yucen.wu23@imperial.ac.uk
    • Principal Investigator: David R Owen
    • Sub-Investigator: Aaron M Lett

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
• Aged 18-75 years old
• A female subject is eligible to participate if she is a) of non-childbearing potential, defined as pre-menopausal females with a documented tubal ligation or hysterectomy, or postmenopausal defined as 12 months of spontaneous amenorrhea or b) of childbearing potential but not pregnant (as determined by urinary pregnancy test on screening and on each study day) and willing to use one of the contraception methods.
• Male subject must agree to use one of the contraception methods.
• No history of diabetes.

Exclusion Criteria:

• Clinically meaningful abnormalities in routine bloods including:

  • eGFR < 60ml/min
  • Elevation of liver enzymes/bilirubin
  • Prolonged prothrombin time
  • Thrombocytopenia

• Use of the following medications or therapies:

  • P450 CY3A4 inhibitors

    • Potent: Boceprevir, Clarithromycin, Cobicistat, Idelalisib, Itraconazole, Ketoconazole, Nelfinavir, Ritonavir, Saquinavir, Telaprevir, Telithromycin, Voriconazoleb
    • Moderate: Aprepitant, Conivaptan, Crizotinib, Diltiazem, Dronedarone, Erythromycin, Fluconazole, Imatinib, Isavuconazole, Nefazodone, Netupitant, Nilotinib, Posaconazolee, Tofisopam, Verapamil
    • Unclassified: Delavirdine

  • P450 CY3A4 inducers

    • Potent: Carbamazepine, Enzalutamide, Fosphenytoin, Mitotane, Phenytoin, Rifampicin
    • Moderate; Bosentan, Efavirenz, St John's wort
    • Unclassified; Barbiturates, Nevirapine, Primidone, Rifabutin, Rifapentine
  • oral contraceptives
  • oral anticoagulants or antiplatelet agents other than low dose aspirin
  • levothyroxine
• Currently breastfeeding.
• Any clinical significant medical conditions that in the opinion of the investigator would compromise subjects' safety or compliance with study procedures.
• History of any clinical condition which in the opinion of the principal investigator would compromise the scientific integrity of the study, such as some chronic systemic diseases affecting blood, liver or kidneys or endocrine system.
• Unwillingness or inability to follow the procedures outlined in the protocol.
• Subject is mentally or legally incapacitated.

• Contraindication to XBD173 use:

  • Hypersensitivity to the active substance or to any of the excipients

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Acute glucose challenege visits; Participants receive a single oral dose of XBD173 90 mg during one study visit and a placebo during the corresponding crossover visit, before an OGTT. The order of the drug and placebo is randomised.	Drug: XBD173; 90mg XBD173 oral dose; Other Names: Emapunil; Drug: Placebo; Participants will receive a placebo drug, identical in appearance to XBD173.
Experimental: Fasting visits; Participants receive a single oral dose of XBD173 90 mg during one study visit and a placebo during the corresponding crossover visit, with participants remaining fasted. The order of the drug and placebo is randomised.	Drug: XBD173; 90mg XBD173 oral dose; Other Names: Emapunil; Drug: Placebo; Participants will receive a placebo drug, identical in appearance to XBD173.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma Glucose Concentration in millimoles per litre During Oral Glucose Tolerance Test	Plasma glucose concentration in millimoles per litre will be measured from venous blood samples during acute glucose challenge visits after administration of XBD173 or placebo. Plasma glucose concentrations at each time point and/or the glucose response over time will be compared between XBD173 and placebo conditions.	Blood samples will be collected at 60, 30, and 10 minutes before the oral glucose tolerance test; at the time of the test; and at 30, 60, 90, 120, 150, and 180 minutes after the test. The oral glucose tolerance test will be administered at 0 minutes.
Fasting Plasma Glucose Concentration in millimoles per litre After XBD173 or Placebo Administration	Fasting plasma glucose concentration in millimoles per litre will be measured from venous blood samples during fasting study visits after administration of XBD173 or placebo. Plasma glucose concentrations at each time point and/or the fasting glucose response over time will be compared between XBD173 and placebo conditions.	Blood samples will be collected at 10 minutes before XBD173 or placebo administration, at administration, and at 30, 60, 90, 120, 150, 180, 210, and 240 minutes after administration.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma Insulin Concentration in milliunits per litre During Oral Glucose Tolerance Test	Plasma insulin concentration in milliunits per litre will be measured from venous blood samples during acute glucose challenge visits after administration of XBD173 or placebo. Plasma insulin concentrations at each time point and/or the glucose response over time will be compared between XBD173 and placebo conditions.	Blood samples will be collected at 60, 30, and 10 minutes before the oral glucose tolerance test; at the time of the test; and at 30, 60, 90, 120, 150, and 180 minutes after the test. The oral glucose tolerance test will be administered at 0 minutes.
Fasting Plasma Insulin Concentration in milliunits per litre After XBD173 or Placebo Administration	Fasting plasma insulin concentration in milliunits per litre will be measured from venous blood samples during fasting study visits after administration of XBD173 or placebo. Plasma insulin concentrations at each time point and/or the fasting glucose response over time will be compared between XBD173 and placebo conditions.	Blood samples will be collected at 10 minutes before XBD173 or placebo administration, at administration, and at 30, 60, 90, 120, 150, 180, 210, and 240 minutes after administration.
Peripheral Endothelial Function Measured by Cuff-Based Assessment	Peripheral endothelial function will be measured using a cuff-based assessment during each study visit and compared between XBD173 and placebo conditions.	Assessed at 10 minutes before the oral glucose tolerance test during acute glucose challenge visits, and at 10 minutes before XBD173 or placebo administration during fasting visits.
Respiratory Quotient Measured by Indirect Calorimetry (Acute Glucose Challenge)	Respiratory quotient will be measured using indirect calorimetry during acute glucose challenge visits and fasting visits after administration of XBD173 or placebo. Respiratory quotient values will be compared between XBD173 and placebo conditions.	Indirect calorimetry will take place from the first study visit to the fourth visit. For acute glucose visits, respiratory quotient will be measured at 140, 90 and 30 minutes prior to OGTT, and 50, 170 minutes after OGTT.
Respiratory Quotient Measured by Indirect Calorimetry (Fasting Visits)	Respiratory quotient will be measured using indirect calorimetry during acute glucose challenge visits and fasting visits after administration of XBD173 or placebo. Respiratory quotient values will be compared between XBD173 and placebo conditions.	Indirect calorimetry will take place from the first study visit to the fourth visit. For fasting visits, respiratory quotient will be measured at 30 minutes prior to XBD173/placebo and 50, 110, 170, 230 minutes after XBD173/placebo.
Adipose Tissue Composition From Subcutaneous Adipose Tissue Biopsy	Adipose tissue composition will be measured from subcutaneous adipose tissue samples collected by percutaneous biopsy during study visits after administration of XBD173 or placebo. Adipose tissue composition will be compared between XBD173 and placebo conditions.	Adipose tissue biopsy will take place from the first study visit to the fourth visit, at 120 minutes after XBD173/placebo.

Collaborators and Investigators

• Sponsor: Imperial College London

Study record dates

Study Major Dates

• Study Start (Actual): March 27, 2026
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): September 1, 2028

Study Registration Dates

• First Submitted: June 9, 2026
• First Submitted That Met QC Criteria: June 26, 2026
• First Posted (Actual): July 2, 2026

Study Record Updates

• Last Update Posted (Actual): July 2, 2026
• Last Update Submitted That Met QC Criteria: June 26, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Healthy Volunteers; OGTT; Glucose Metabolism; Oral Glucose Tolerance Test; Resting Energy Expenditure; TSPO; XBD173; Fasting Plasma Glucose; Insulin Response; Placebo-Controlled Trial; 18 kDa Translocator Protein; Respiratory Quotient; Randomised Controlled Trials; Randomised Crossover Study
• Additional Relevant MeSH Terms: N-benzyl-N-ethyl-2-(7,8-dihydro-7-methyl-8-oxo-2-phenyl-9H-purin-9-yl)acetamide
• Other Study ID Numbers: 23HH8619; 334773 (Registry Identifier: Integrated Research Application System (IRAS)); 24/LO/0127 (Registry Identifier: Research Ethics Committee (REC))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Study sponsored by Imperial College London. Researchers will not breach the data violation policy.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No