The Therapeutic Potential of Mesenchymal Stem Cell-derived Exosomes in Peritoneal Dysfunction

A Phase I, Single-center, Open-label Study to Evaluate the Safety, Tolerability, and Dose-finding of Mesenchymal Stem Cell-derived Exosomes in the Treatment of Peritoneal Dialysis-related Peritoneal Dysfunction

The goal of this clinical trial is to learn if a single intraperitoneal infusion of mesenchymal stem cell-derived exosomes (MSC-Exos) is safe and tolerable in adults with peritoneal dialysis-related peritoneal failure. It will also explore whether MSC-Exos might improve how well the peritoneum works (ultrafiltration and solute transfer).

The main questions it aims to answer are:

What is the highest single dose of MSC-Exos that can be given safely without causing unacceptable side effects? (This helps find the maximum tolerated dose and the dose to use in future phase II studies.)

What medical problems (adverse events) do participants experience after receiving MSC-Exos?

Does MSC-Exos show any early signs of improving ultrafiltration volume and solute transport across the peritoneum?

Researchers will test increasing doses of MSC-Exos in small groups of participants. Each participant will receive one dose of MSC-Exos added to their usual 1.5% glucose dialysis solution (2 litres), which is then left in the abdominal cavity for 8 hours. The study does not use a placebo; instead, different dose levels are tested one after another to find the safest and most promising dose.

Participants will:

Receive a single intraperitoneal infusion of MSC-Exos through their dialysis catheter

Be monitored closely before the infusion；

Attend follow-up visits at 24 hours, 72 hours, 2 weeks, and 4 weeks after the dose;

Have blood and peritoneal effluent samples taken at each visit to check for safety ;

Have their ultrafiltration volume and solute transport ability measured at baseline and 4 weeks after the dose to see if any changes occur.

All participants will be closely observed for any side effects. The results will help decide whether further studies are warranted.

Inclusion Criteria:

1. Patients who have been on continuous peritoneal dialysis for more than 1 year.

2. Age ≥ 18 years.

3. Patients meeting at least one of the following criteria for peritoneal ultrafiltration insufficiency:

   • Standard PET-confirmed ultrafiltration failure: 4-hour ultrafiltration volume < 400 mL using 4.25% glucose dialysate, or < 100 mL using 2.5% glucose dialysate; ② 1-hour sodium dip < 5 mmol/L and/or 1-hour sodium sieve ratio ≤ 0.03 using 4.25% glucose dialysate; ③ Inability to maintain fluid balance, as evidenced by persistent edema/heart failure symptoms, NT-proBNP >11215.2 ng/L, or bioimpedance spectroscopy-assessed overhydration (OH) >2 L (after excluding non-peritoneal causes).

Exclusion Criteria:

1. Patients with acute renal failure or chronic renal failure who can be temporarily weaned from dialysis.
2. Patients with malignant tumors, active infections, or severe malnutrition.
3. Patients with severe hepatic failure or cirrhosis.
4. Patients with severe cardiovascular disease, severe heart failure (NYHA Class IV or higher), or active systemic diseases.
5. Patients with peritonitis within the past 3 months or currently experiencing peritonitis.
6. Patients with encapsulating peritoneal sclerosis (EPS).
7. Patients with peritoneal dialysis catheter dysfunction.
8. Planned or ongoing pregnancy.
9. Simultaneous participation in another interventional clinical trial or drug study.