Metabolism of Ornithine Phenylacetate (OCERA OP)

Human Metabolism of Ornithine Phenylacetate: A Study in Healthy Volunteers

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.

Study Overview

• Status: Unknown
• Conditions: Healthy
• Intervention / Treatment: Other: phenylacetate salt of ornithine

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Texas
    • College Station, Texas, United States, 77843-4253
      • Texas A&M University-CTRAL

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: phenylacetate salt of ornithine; 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Texas A&M University
• Collaborators: Ocera Therapeutics

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 1, 2015
• Primary Completion (ACTUAL): April 1, 2015
• Study Completion (ANTICIPATED): April 1, 2021

Study Registration Dates

• First Submitted: May 16, 2017
• First Submitted That Met QC Criteria: May 16, 2017
• First Posted (ACTUAL): May 18, 2017

Study Record Updates

• Last Update Posted (ACTUAL): April 11, 2019
• Last Update Submitted That Met QC Criteria: April 10, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: dietary supplements
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Phenylacetic acid
• Other Study ID Numbers: 2014-0801

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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