None listed
Conditions
Brief summary
Albumin is the most abundant protein in plasma. It has several important functions, but the plasma concentration decreases in inflammation, trauma and in connection with major surgery. There is a wide spread use of intravenous albumin infusions in these situations, but the evidence of benefit is sparse. One reason for the lack of consensus is the lack of knowledge regarding albumin kinetics. Albumin synthesis can be investigated by stable isotope labeled amino acids and the flooding dose technique. Repeated measures is a valuable tool to assess the effect of interventions, and the quality of such measures would be improved by using different labels. The aim of this investigation is to validate two different isotopically labeled amino acids for assessment of albumin synthesis rate. Also synthesis rates of other plasma proteins, such as fibrinogen, will be measured. By using different time intervals we will be able to optimize the design of planned studies on albumin kinetics in surgical and critically ill patients.
Interventions
Healthy volunteers will repeatedly receive intravenous 10 min infusions of amino acids labeled with stable isotopes to assess albumin and fibrinogen fractional synthesis rates by measuring the increase of labels in the two plasma proteins, respectively. Either d5-phenylalanine (d5-Phe) or d8-phenylalanine (d8-Phe) will be used together with unlabeled phenylalanine (Phe). All infusions will contain a combined amount of labeled and unlabeled phenylalanine of 45 mg/kg body weight dissolved in steri
Healthy volunteers will repeatedly receive intravenous 10 min infusions of amino acids labeled with stable isotopes to assess albumin and fibrinogen fractional synthesis rates by measuring the increase of labels in the two plasma proteins, respectively. Either d5-phenylalanine (d5-Phe) or d8-phenylalanine (d8-Phe) will be used together with unlabeled phenylalanine (Phe). All infusions will contain a combined amount of labeled and unlabeled phenylalanine of 45 mg/kg body weight dissolved in sterile water to a concentration of 20 mg/ml. Only the proportion between the two labels and Phe will vary between the occasions. No other fluid will be given. All subjects will serve as their own controls. In protocol 1a, volunteers (n=5) will receive a 10 min infusion of unlabeled Phe with 10 atom percent excess (APE) d5-Phe on day 1. APE is defined as 100*tracer/(tracer+tracee) where unlabled Phe is the tracee. On the second occasion day 3 the 10 min infusion will consist of unlabeled Phe and 10 APE d8-Phe. The combined amount of labeled and unlabeled phenylalanine will be 45 mg/kg body weight on each occasion. In protocol 1b, volunteers (n=5) will receive a 10 min infusion of unlabeled Phe and 10 APE d8-Phe on day 1. On the second occation day 3 the 10 min infusion will consist of unlabeled Phe and 10 APE d5-Phe. The combined amount of labeled and unlabeled phenylalanine will be 45 mg/kg body weight on each occasion. In protocol 1, n=10 volunteers will be studied at day 1 and day 3, thus in total receive 2 infusions of mixed labeled and unlabeled phenylalanine. In protocol 2, volunteers (n=6) will receive a 10 min infusion of unlabeled Phe mixed with 10 APE d5-Phe in the morning of day 1, and, after approximately five hours, on occasion 2 the 10 min infusion will consist of unlabeled Phe with 10 APE d8-Phe. Finally, on the third occasion day 8 the 10 min infusion will consist of unlabeled Phe with 20 APE d5-Phe. The combined amount of labeled and unlabeled phenylalanine will be 45 mg/kg body weight on each occasion. The volunteers in protocol 2 will be studied at day 1 in the morning, day 1 in the afternoon (after approximately 5 hrs), and on day 8, thus in total receive 3 short infusions. The size of the plasma pool will be determined by anthropometric calculation of plasma volume and plasma-albumin and plasma-fibrinogen, respectively, which makes determination of absolute synthesis rate possible.
Sponsors
Jan Wernerman
Study design
Allocation
Non-randomised trial
Primary purpose
Diagnosis
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
healthy volunteers
Exclusion criteria
Age < 18 years Participation in other trial within 2 months
Outcome results
None listed