Effect Camostat for Kidney Protection in Chronic Kidney Disease

Обзор

This clinical trial aims to evaluate the effects of Camostat Mesylate, a serine protease inhibitor, in patients with chronic kidney disease (CKD) and proteinuria. Proteinuria accelerates CKD progression and increases cardiovascular risks. By inhibiting serine protease activity and tubular complement activation, camostat may mitigate progressive kidney injury, potentially improving clinical outcomes. This is an interventional, non-randomized, open-label pharmacodynamic trial that includes CKD patients with proteinuria and healthy controls. This approach has been chosen as the trial serves as a pilot study, aiming to investigate a novel treatment target in CKD patients. Including healthy controls allows a comparison of the effect of Camostat Mesilate on normal physiology versus CKD with proteinuria. Participants will: * Follow a standardized sodium diet of 150 mmol/day for 8 days. * Receive oral Camostat Mesilate (200 mg thrice daily) for four days (day 5-8 on the diet). * Provide blood and urine samples, record blood pressure, and undergo body composition measurements at baseline, during intervention, and at study completion. The primary effect parameters are urine sodium and water excretion, body water content/weight, and home blood pressure. Secondary endpoints are tubular complement activation, urine protease activity, ENaC activation, 24-hour urine albumin excretion, and plasma concentrations of renin, angiotensin II, aldosterone, and NT-proBNP.

Подробное описание

Please refer to the protocol.

Вмешательства

• Препарат Camostat Mesylate
  Oral Camostat Mesylate 200 mg x 3 daily for 4 days.

Первичные конечные точки

• 24 h Urine sodium excretion (mmol/day) [Срок оценки: At baseline (day 0), before treatment with IMP (day 5), and after completion of 4 days treatment with IMP (day 9).]
• Water excretion (L) [Срок оценки: At baseline (day 0), before treatment with IMP (day 5), and after completion of 4 days treatment with IMP (day 9).]
• Total Body Water (L) [Срок оценки: At baseline (day 0), before treatment with IMP (day 5), and after completion of 4 days treatment with IMP (day 9).]
• Home blood pressure [Срок оценки: At baseline (day 0), before treatment with IMP (day 5), and after completion of 4 days treatment with IMP (day 9).]

Вторичные конечные точки (6)

• Urine protease activity: zymography + protease activity [Срок оценки: At baseline (day 0), before treatment with IMP (day 5), and after completion of 4 days treatment with IMP (day 9).]
• Tubular complement activation [Срок оценки: At baseline (day 0), before treatment with IMP (day 5), and after completion of 4 days treatment with IMP (day 9).]
• Urine microvesicles: gammaENaC cleavage [Срок оценки: At baseline (day 0), before treatment with IMP (day 5), and after completion of 4 days treatment with IMP (day 9).]
• Urine microvesicles: complement deposition [Срок оценки: At baseline (day 0), before treatment with IMP (day 5), and after completion of 4 days treatment with IMP (day 9).]
• 24 hours urine albumin excretion (mg/day) [Срок оценки: At baseline (day 0), before treatment with IMP (day 5), and after completion of 4 days treatment with IMP (day 9).]
• Plasma concentration of renin, NT-proBNP, angiotensin II and aldosterone [Срок оценки: At baseline (day 0), before treatment with IMP (day 5), and after completion of 4 days treatment with IMP (day 9).]

Критерии участия

Patients:

Критерии включения

• Age ≥ 18 years.
• A clinical diagnosis of CKD of any course and meet the following criteria at screening:

• eGFR ≥ 30 ml/min/1.73m2
• U-ACR ≥ 300 mg/g.
• Stable antihypertensive treatment 2 weeks before start of investigated medical drug (IMP) and maintain this treatment throughout the study.
• Office blood pressure at the screening session should be >120/70 mmHg and <150/90 mmHg.
• Capable of providing a signed informed consent and comply with study requirements.
• Women with childbearing potential must have a negative pregnancy test (urine hCG) at spot urine at the screening visit and should use contraception during the study and until one week after completion of study treatment.

Критерии исключения

• Treatment with Amiloride, Spironolactone, Aldosterone, or analogues.
• Treatment with NSAIDs.
• Hyperkalemia > 5.0 mmol/L at screening.
• P-bilirubin > 25 umol/L at screening.
• Ongoing cancer treatment.
• Treatment with immunosuppressive therapy within 6 months prior to screening.
• History of organ transplantation.
• Evidence of current infection (CRP>50 or temperature > 38 C°).
• Severe hepatic insufficiency classified as Child-Pugh C.
• Breastfeeding.
• Congestive heart failure NYHA class IV, unstable or acute congestive heart failure.
• Recent cardiovascular events < 2 months prior to screening:

• Coronary artery revascularization.
• Acute stroke or TIA.
• Acute coronary syndrome.
• Allergy or hypersensitivity to the IMP.
• Addison's disease.
• Gastric bypass operation.
• Lactose intolerance since lactose serves as one of the inactive ingredients in the IMP.
• Participation in other clinical trials within the last 30 days.

Healthy controls:

Критерии включения

• Age ≥ 18 years.
• Good general health with no significant medical conditions or chronic illness (e.g., diabetes, hypertension, cardiovascular disease, autoimmune diseases, and cancer).
• Normal kidney function and no proteinuria at screening:

• eGFR > 90 ml/min/1.73m2
• U-ACR < 30 mg/g
• Office blood pressure at the screening < 140/90 mmHg.
• Capable of providing a signed informed consent and comply with study requirements.

7\. Women with childbearing potential\* must have a negative pregnancy test (urine hCG) at spot urine at the screening visit and should use contraception during the study and until one week after completion of study treatment.

Критерии исключения

• Treatment with any prescription medication except oral contraceptives.
• Use of NSAIDs (Non-Steroidal Anti-Inflammatory Drugs)
• Hyperkalemia > 5.0 mmol/L at screening.
• P-bilirubin > 25 umol/L at screening.
• Evidence of current infection (CRP>50 or temperature > 38 C°).
• Breastfeeding.
• History of substance abuse including alcohol.
• Allergy or hypersensitivity to the IMP.
• Gastric bypass operation.
• Lactose intolerance since lactose serves as one of the inactive ingredients in the IMP.
• Participation in other clinical trials within the last 30 days

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

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Дания · 1 центр

• Department of Nephrology, Odense University Hospital — Odense

Идентификаторы

NCT: NCT06794593 · EUCT 2023-508516-34-00 · 2023-508516-34-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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