Metabolism of Ornithine Phenylacetate

Study Overview
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Brief Summary
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Intravenous infusion of stable tracers of ornithine, glutamine, glutamate, and glycine will be performed, and collect blood samples, urine samples, and muscle biopsies to evaluate the effect of a continuous oral intake of phenylacetate salt of ornithine (OP) on its metabolic fate.

Detailed Description
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The study involves 1 screening visit of approximately 1 hour and 4 study days of approximately 10 hours. The subject will be asked to arrive in the fasted state on all study days. Fasting prior to screening is not required. On the screening day, body weight and height will be measured and Dual-energy X-ray absorptiometry (DXA) will be performed to measure body composition. After 4 hours subjects received a continuous intravenous infusion with OP in a dosage of 1 g /h. Next to the stable tracers provided to determine OP metabolism, stable tracers of phenylalanine (PHE) and tyrosine (TYR) may be provided to determine the effect of OP on protein metabolism at plasma and muscle tissue level. This required 2 muscle biopsies and on 2 study days 1 set of stable tracer pulses.

Official Title
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Human Metabolism of Ornithine Phenylacetate: A Study in Healthy Volunteers

Conditions
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Healthy

Intervention / Treatment
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* Other: phenylacetate salt of ornithine


Participation Criteria
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Eligibility Criteria
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Inclusion criteria healthy subjects: Healthy male & female according to the investigator's or appointed staff's judgment Age 40-70 years (to be comparable with patients with liver cirrhosis: average 54.1 +/- 9.4 years) Exclusion Criteria Metabolic diseases including diabetes and hepatic or renal disorders Presence of acute illness or metabolically unstable chronic illness Failure to give informed consent (Possible) pregnancy Any other condition according to the PI or nurse that would interfere with the study or safety of the patient or influence the results Unwilling to stop taking nutritional protein supplements within 5 days before test day History of hypo- or hyper-coagulation disorders, including use of a Coumadin derivative, history of deep venous thrombosis (DVT), or pulmonary embolism (PE) at any point in lifetime Currently taking anti-thrombotics (i.e. medical indication) and cannot stop for 3-7 days prior to test days Allergy to local anesthetic

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: phenylacetate salt of ornithine<br>There are 4 study days of approximately 10 hours. Amino acid tracers (e.g., OP, PHE, TYR) will be provided via IV. The dosage of OP provided in this study 6 g in a period of 6 hours. 2 muscle biopsies will be completed on 2 of the study days. | Other: phenylacetate salt of ornithine<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| metabolism of ornithine phenylacetate to glutamate and glutamine | The incorporation of the N atoms of ORN into glutamate, and the quantitative contribution of both pathways will be traced, and when the enrichment of ORN and GLU is measured in muscle tissue, give an estimation of the importance of muscle OAT for this incorporation. | 4 study days that are 8 hours each | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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dietary supplements