Effect Camostat for Kidney Protection in Chronic Kidney Disease (CamKid)

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.

Study Overview

• Status: Recruiting
• Conditions: Chronic Kidney Disease(CKD)
• Intervention / Treatment: Drug: Camostat Mesylate

Detailed Description

Please refer to the protocol.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Claus Bistrup, MD, Professor; Phone Number: +4523368077; Email: Claus.Bistrup@rsyd.dk
• Study Contact Backup: Name: Mette B. Boes, MD; Phone Number: +4522919808; Email: mette.boye.boes@rsyd.dk

Study Locations

• Denmark
  • Odense, Denmark, 5000
    • Recruiting
    • Department of Nephrology, Odense University Hospital
    • Contact: Claus Bistrup, MD, Professor; Phone Number: +4523368077; Email: Claus.Bistrup@rsyd.dk
    • Contact: Mette B Boes, MD; Phone Number: +4522919808; Email: mette.boye.boes@rsyd.dk
    • Sub-Investigator: Mette B Boes, MD

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Chronic Kidney Disease patients; Patients with chronic kidney disease. eGFR > 30 ml/min/1,73 m^2 and U-ACR > 300 mg/g.	Drug: Camostat Mesylate; Oral Camostat Mesylate 200 mg x 3 daily for 4 days.; Other Names: Foipan
Experimental: Healthy Controls; Healthy males and females in good general health and with no significant medical conditions or chronic illness.	Drug: Camostat Mesylate; Oral Camostat Mesylate 200 mg x 3 daily for 4 days.; Other Names: Foipan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
24 h Urine sodium excretion (mmol/day)		At baseline (day 0), before treatment with IMP (day 5), and after completion of 4 days treatment with IMP (day 9).
Water excretion (L)	24 h urine collection	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)	Measured by Body Composition Monistor	At baseline (day 0), before treatment with IMP (day 5), and after completion of 4 days treatment with IMP (day 9).
Home blood pressure		At baseline (day 0), before treatment with IMP (day 5), and after completion of 4 days treatment with IMP (day 9).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Urine protease activity: zymography + protease activity		At baseline (day 0), before treatment with IMP (day 5), and after completion of 4 days treatment with IMP (day 9).
Tubular complement activation	Urine C3a, MAC-sC5b-9, C3dg, MBL	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		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		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)		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		At baseline (day 0), before treatment with IMP (day 5), and after completion of 4 days treatment with IMP (day 9).

Collaborators and Investigators

• Sponsor: Odense University Hospital
• Investigators: Study Director: Claus Bistrup, MD, Professor, Department of Nephrology, Odense University Hospital, Denmark

Study record dates

Study Major Dates

• Study Start (Actual): November 21, 2024
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): February 28, 2027

Study Registration Dates

• First Submitted: January 10, 2025
• First Submitted That Met QC Criteria: January 21, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 21, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: Chronic Kidney Disease; CKD; Complement; Proteinuria; Albuminuria; ENaC; Epithelial Sodium Channel; Camostat Mesylate; Serine Protease Inhibitor; Proteaseuria
• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Chronic Disease; Disease Attributes; Renal Insufficiency; Kidney Diseases; Renal Insufficiency, Chronic; Molecular Mechanisms of Pharmacological Action; Protease Inhibitors; Enzyme Inhibitors; Serine Proteinase Inhibitors; Trypsin Inhibitors; Camostat
• Other Study ID Numbers: EUCT 2023-508516-34-00; 2023-508516-34-00 (Ctis)

Drug and device information, study documents

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