Randomized Multicenter Cross-over Study to Compare the Effect of Physioneal 35 to 40 on the Protein Metabolism

Randomized, Multicenter Cross-over Study in Investigating the Effect of Bicarbonate-based Solutions (Physioneal 35 vs. 40) on Protein Metabolism in Children and Adolescents on Chronic Peritoneal Dialysis

The purpose of this study is to demonstrate an increase in protein metabolism during treatment with Physioneal 35® (containing lactate 10 mmol/l, calcium 1.75 mmol/l) compared to treatment with Physioneal 40® (containing lactate 15 mmol/l, calcium 1.25 mmol/l) in children and adolescents with end stage renal failure receiving peritoneal dialysis.

• Fat oxidation (13C-enrichment in expiration breath samples for U-C13-algae turnover)
• Growth markers (plasma levels of IgF-1, IgF-BP3, leptin)
• Biochemical markers of anabolism (plasma levels of total protein, albumin, transferrin)
• Serum thyroid function (fT3, fT4, TSH)
• Serum lipid status
• Serum markers of calcium/phosphate metabolism (PTH, calcium, ionized calcium, phosphate, alkaline phosphatase)
• Prevalence of metabolic acidosis/ alkalosis (venous sample), serum lactate
• Safety parameters (such as normalized weekly Kt/v, parameters of glucose metabolism, parameters of hepatic function, parameters of calcium-phosphate-metabolism, physical examination incl. standing height, weight, assessment of complications related to peritoneal dialysis as peritonitis, exit infections and inguinal hernia)
• Body composition (lean body mass and body fat mass/fluid)

Inclusion Criteria:

• Patients who are males or non-pregnant females between the ages of 3 months and 18 years.
• Patients who are on regular automated peritoneal dialysis due to end stage renal failure for at least 3 months.
• Patients and/or their parents must be capable of understanding the purpose and risks of the study.
• Patients and/or their parents (or guardians) who are willing to give written informed consent and willing to participate in and comply with the study protocol.

Exclusion Criteria:

• Use of pure lactate, amino acid or oligosaccharide solutions for peritoneal dialysis

• Peritonitis episode less than 6 weeks before enrolment

• Hypercalcemia (serum) > 2.75 mmol/l in three independent measurements during 10 days

• Severe secondary hyperthyroidism (iPTH > 500 ng/l)

• Renal anemia with hemoglobin (blood) < 10 mg/dl

• Impaired hepatic function (AST/SGOT or ALT/SGPT > 2 times the upper limit of the reference range)

• Patients who are participating in another study that requires Ethics Committee approval. Non-interventional studies are permitted.

• Pregnant female patients, females of childbearing potential who are unwilling or unable to use adequate contraception methods.

• Severe respiratory insufficiency

• Malnourishment (body weight < -2.5 SDS for height and gender) or severe deterioration of fat metabolism

• Patients with a history of malignancy of any organ system, treated or untreated

• Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of the investigational product and the comparator, including

  • Major deterioration of the abdominal wall (e.g. dermal infections or burns, hernia)
  • Major deterioration of the abdominal cavity (e.g. ascites, ileus, adhesions, bowel perforation, defects of the diaphragm, tumours)

• Patients with a history of viral infections such as HIV or hepatitis B, C.