Single and Multiple Doses of an Oral Formulation of L-Homoarginine in Healthy Human Subjects

Study Overview
=================
Brief Summary
-----------------
This study represents an initial clinical evaluation of an oral formulation of L-homoarginine. L-homoarginine and L-arginine are amino acids found in food proteins and are both substrates for nitric oxide synthase (NOS). L-arginine is available as over the counter nutraceutical. This study will provide information on the dosing of L-homoarginine in order to reach high physiological plasma concentrations in humans.

Detailed Description
-----------------
Study Design In a randomized, double-blind, placebo-controlled cross-over design participants receive either L-homoarginine 125 mg or placebo once daily in the morning for four weeks each. The study periods are separated by a washout phase of four weeks, and the sequence of the medications is randomly chosen in each participant. The study is preceded by a run-in phase, where all participant receive a single dose of 125 mg L-homoarginine. Blood samples (2.7 ml ethylenediaminetetraacetic acid vacutainer) for plasma L-homoarginine determinations are drawn at time points 0, 15 min, 30 min, 1, 2, 4, 8, 24, 48, 72, and 120 hours after single and multiple doses of L-homoarginine and placebo, respectively. At baseline and four weeks after each supplementation period (hArg and placebo), routine laboratory, arginine, asymmetric dimethylarginine, pulse wave velocity, augmentation index, flow-mediated vasodilatation, transcranial magnetic stimulation, and test battery of attentional performance are evaluated as secondary endpoints. Study Duration One year Sample Size Calculation and Statistical Evaluation Due to the exploratory nature of this pilot study, exploratory statistical methods will be used for statistical evaluation of the study results, and no formal sample size calculation was performed. In a previous study 20 participants were included to assess the kinetic, dynamic, and safety profile of L-citrulline and L-arginine [Schwedhelm et al. 2007]. Statistical comparisons will be performed using two-sided tests, i.e. Student's t-test and ANOVA. A p < 0.05 will be considered significant.

Official Title
-----------------
Study to Evaluate the Safety, Tolerability, Kinetics, and Dynamics of Single and Multiple Doses of an Oral Formulation of L-Homoarginine

Conditions
-----------------
Healthy

Intervention / Treatment
-----------------
* Dietary Supplement: L-Homoarginine
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female, 20-75 years of age on the day of dosing and is generally healthy as determined by medical history, physical examination, and laboratory test values For females, postmenopausal for at least 2 years prior to screening (confirmed by a negative hormone panel, i.e., plasma 17β-estradiol concentration of <20 pg/mL and follicle-stimulating hormone level of >40 IU/mL) or contraception Has signed and received a copy of the written informed consent form approved by the investigator's Independent Ethics Committee (IEC), understands the purposes and risks of the study and agrees to follow the restrictions and schedule of procedures as defined by the study protocol Exclusion Criteria: Sitting blood pressure greater than 160/100 or less than 90/60 mm Hg Sitting heart rate greater than 99 bpm or less than 50 beats per minute (bpm) History of clinically significant hypotensive episodes or symptoms of fainting, dizziness, or light-headedness Body Mass Index (BMI) greater than 32 or less than 16 at screening [BMI = Weight (kg) ÷ Height2 (m2)] History or symptoms of cardiovascular disease, particularly coronary artery disease, arrhythmias,or congestive heart failure History of significant central nervous system disease, including transient ischemic attack, stroke, seizure disorder, or behavioral disturbances

Ages Eligible for Study
-----------------
Minimum Age: 20 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: L-Homoarginine<br>125 mg of L-homoarginine | Dietary Supplement: L-Homoarginine<br>* 125 mg L-homoarginine once daily<br>|
| Placebo Comparator: Placebo<br>placebo capsules | Drug: Placebo<br>* placebo capsules once daily<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma concentration versus time curve (AUC) | To determine the AUC of L-homoarginine (a) following a single oral dose and (b) following administration of multiple oral doses of L-homoarginine. | 1 Month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak plasma concentration (Cmax) | To determine the Cmax of L-homoarginine (a) following a single oral dose and (b) following administration of multiple oral doses of L-homoarginine. | 1 Month | 
| Half life of plasma concentration (t1/2) | To determine the t1/2 of L-homoarginine (a) following a single oral dose and (b) following administration of multiple oral doses of L-homoarginine. | 1 Month | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
kinetic data, volunteers