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Набор скоро начнётся NCT06626984

Investigation of Novel and Established Therapies in a Human Intravenous Lipopolysaccharide Model of Sepsis

Фаза I / Фаза II С лечением Sepsis Fluid Overload Endothelial Dysfunction Microcirculation

Ориентир для пациента и семьи

Простыми словами

Автоматическая сводка по структурированным данным реестра. Она помогает сориентироваться, но не заменяет официальный протокол или оценку врача.

Что изучают
В протоколе указаны: Imatinib, Compound sodium lactate solution.
Кому может быть актуально
Состояния в реестре: Sepsis, Fluid Overload, Endothelial Dysfunction, Microcirculation. Базовые параметры: 18 лет — 40 лет · Все.
Что важно проверить
Возраст, диагноз и пол — только базовые ориентиры. Предыдущее лечение, анализы и другие обязательные условия указаны ниже в критериях участия.
Где проводится
Список центров уточняется — проверьте первичный протокол.
Следующий шаг
Сохраните исследование, покажите его лечащему врачу и уточните актуальный статус у исследовательского центра. Расходы, документы и поездка →

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Обзор

Sepsis is a common and life-threatening condition caused by a dysregulated host immune response to infection. Given the prominent role of endothelial breakdown and dysfunction in sepsis, therefore, there is an urgent need to establish strategies to protect the endothelium and preserve microcirculatory function. This study is a randomised clinical study investigating intravenous fluid therapy and oral imatinib therapy in healthy human volunteers exposed to intravenous lipopolysaccharide (LPS). The objective of the study is to investigate the biological effects of fluid and imatinib therapy on LPS-induced microcirculatory dysfunction.

Подробное описание

The benefits of intravenous fluid administration in sepsis remain uncertain. A growing body of evidence suggests that excessive fluid administration is harmful. An association between a more positive fluid balance and mortality in critically ill patients has been repeatedly demonstrated. Moreover, emerging evidence suggests that intravenous fluid administration induces glycocalyx injury, thought to be mediated by shear stress. In sepsis the rapid administration of intravenous fluids is hypothesised to exacerbate glycocalyx injury, capillary leak and tissue oedema formation.

Recent work has highlighted the protective effects of Imatinib, a tyrosine kinase inhibitor, on endothelial barrier function in animal models of microcirculatory dysfunction as well as in patients with endothelial barrier dysfunction. Moreover, Imatinib has also been demonstrated to attenuate markers of systemic inflammation in animals with a LPS-induced lung injury model of acute respiratory distress syndrome. There is, therefore, a growing body of evidence to support a potential therapeutic role for Imatinib in disease states involving inflammatory vascular leak.

The hypothesis being tested is that:

1. Intravenous fluid therapy will exacerbate the degree of vascular dysfunction and systemic inflammation observed in this model. 2. Imatinib pre-treatment will attenuate the degree of vascular dysfunction and systemic inflammation observed in this model.

Вмешательства

  • Препарат Imatinib
    Pre-treatment with 600mg Imatinib administered 1 hour prior to intravenous LPS.
  • Препарат Compound sodium lactate solution
    Total of 30 ml/kg administered 90 minutes following intravenous LPS. 30mls/kg (maximum volume of 2500mls) administered in two divided doses (15mls/kg) intravenously. Each bolus will be administered at a fixed rate of 999mls/hr.

Первичные конечные точки

  • Biomarkers of vascular and glycocalyx injury [Срок оценки: Up to 8 hours following LPS administration]
Вторичные конечные точки (3)
  • Biomarkers of inflammation [Срок оценки: Up to 8 hours following LPS administration]
  • Venous Excess Ultrasound Score [Срок оценки: Up to 8 hours following LPS administration]
  • B-lines [Срок оценки: Up to 8 hours following LPS administration]

Критерии участия

Критерии включения

  • Healthy adult volunteers aged between 18 and 40 years of age
  • Informed consent to participate

Критерии исключения

  • Current participation in a clinical trial
  • Pregnant or breastfeeding
  • Current history of smoking
  • Alcohol intake > 21 units per week
  • Regular intake of any relevant prescription or over-the-counter medication. Any regular medication use will be reviewed on a case-by-case basis as to (a) risk and (b) potential confounding effect.
  • Oxygen saturation <95% breathing room air
  • Abnormal findings on history, examination or laboratory tests suggestive of underlying illness (in the opinion of the clinician undertaking screening)
  • History of recurrent vaso-vagal episodes
  • Allergy to Imatinib
  • Positive or equivocal hepatitis B or C serology result

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

Здоровые добровольцы: Да

Дизайн исследования

Распределение
Рандомизированное
Модель
Факторный дизайн
Маскирование
Двойное слепое
Основная цель
Фундаментальное исследование

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT06626984 · 22064JS-AS

Первоисточники (государственные реестры)

Открыть это исследование на ClinicalTrials.gov ↗