Clinical trial NCT06794593: Effect Camostat for Kidney Protection in Chronic Kidney Disease
Official title: Effect Camostat for Kidney Protection in Chronic Kidney Disease
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Chronic Kidney Disease(CKD)
Keywords: CKD
Chronic Kidney Disease
Proteinuria
Camostat Mesylate
Serine Protease Inhibitor
Complement
ENaC
Epithelial Sodium Channel
Albuminuria
Proteaseuria
Lead sponsor: Odense University Hospital
Sponsor class: OTHER
First posted: 2025-01-27
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a single-center, interventional, non-randomized, open-label pharmacodynamic study designed to evaluate the effects of Camostat Mesilate in patients with chronic kidney disease (CKD) and proteinuria compared to healthy controls. A total of 40 participants (20 CKD patients and 20 healthy controls matched by age and gender) will follow a standardized sodium diet (150 mmol/day) for 8 days. On the fifth day, participants will begin a 4-day course of oral Camostat (200 mg three times daily), while continuing the sodium-controlled diet. CKD patients will receive CM as an add-on to their standard treatment. Blood samples, 24-hour urine collections, home blood pressure measurements, and body composition monitoring will be performed at baseline, after 4 days on the diet, and after completing the Camostat treatment.
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: Please refer to the protocol.

Eligibility criteria: Patients:

Inclusion criteria:

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

   1. eGFR ≥ 30 ml/min/1.73m2
   2. U-ACR ≥ 300 mg/g.
3. Stable antihypertensive treatment 2 weeks before start of investigated medical drug (IMP) and maintain this treatment throughout the study.
4. Office blood pressure at the screening session should be \>120/70 mmHg and \<150/90 mmHg.
5. Capable of providing a signed informed consent and comply with study requirements.
6. 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.

Exclusion criteria:

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

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

Healthy controls:

Inclusion criteria:

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

   1. eGFR \> 90 ml/min/1.73m2
   2. U-ACR \< 30 mg/g
4. Office blood pressure at the screening \< 140/90 mmHg.
5. 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.

Exclusion criteria:

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

Primary outcomes:
measure: 24 h Urine sodium excretion (mmol/day)
timeFrame: At baseline (day 0), before treatment with IMP (day 5), and after completion of 4 days treatment with IMP (day 9).
measure: Water excretion (L)
timeFrame: At baseline (day 0), before treatment with IMP (day 5), and after completion of 4 days treatment with IMP (day 9).
measure: Total Body Water (L)
timeFrame: At baseline (day 0), before treatment with IMP (day 5), and after completion of 4 days treatment with IMP (day 9).
measure: Home blood pressure
timeFrame: At baseline (day 0), before treatment with IMP (day 5), and after completion of 4 days treatment with IMP (day 9).
Secondary outcomes:
measure: Urine protease activity: zymography + protease activity
timeFrame: At baseline (day 0), before treatment with IMP (day 5), and after completion of 4 days treatment with IMP (day 9).
measure: Tubular complement activation
timeFrame: At baseline (day 0), before treatment with IMP (day 5), and after completion of 4 days treatment with IMP (day 9).
measure: Urine microvesicles: gammaENaC cleavage
timeFrame: At baseline (day 0), before treatment with IMP (day 5), and after completion of 4 days treatment with IMP (day 9).
measure: Urine microvesicles: complement deposition
timeFrame: At baseline (day 0), before treatment with IMP (day 5), and after completion of 4 days treatment with IMP (day 9).
measure: 24 hours urine albumin excretion (mg/day)
timeFrame: At baseline (day 0), before treatment with IMP (day 5), and after completion of 4 days treatment with IMP (day 9).
measure: Plasma concentration of renin, NT-proBNP, angiotensin II and aldosterone
timeFrame: At baseline (day 0), before treatment with IMP (day 5), and after completion of 4 days treatment with IMP (day 9).
Other outcomes:
Locations:
city: Odense
country: Denmark
facility: Department of Nephrology, Odense University Hospital
Study officials:
affiliation: Department of Nephrology, Odense University Hospital, Denmark
name: Claus Bistrup, MD, Professor
role: STUDY_DIRECTOR
References: