Role of a Mitochondrial Receptor in Blood Sugar Regulation

Официальное название

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

Обзор

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.

Вмешательства

• Препарат XBD173
  90mg XBD173 oral dose
• Препарат Placebo
  Participants will receive a placebo drug, identical in appearance to XBD173.

Первичные конечные точки

• Plasma Glucose Concentration in millimoles per litre During Oral Glucose Tolerance Test [Срок оценки: 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 [Срок оценки: 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.]

Вторичные конечные точки (6)

• Plasma Insulin Concentration in milliunits per litre During Oral Glucose Tolerance Test [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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) [Срок оценки: 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) [Срок оценки: 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 [Срок оценки: Adipose tissue biopsy will take place from the first study visit to the fourth visit, at 120 minutes after XBD173/placebo.]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Перекрёстный дизайн

Маскирование

Четверное слепое

Основная цель

Фундаментальное исследование

Центры проведения

Великобритания · 1 центр

• NIHR Trust Imperial Clinical Research Facility — London

Идентификаторы

NCT: NCT07682233 · 23HH8619 · 334773 · 24/LO/0127

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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