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

Phase 1

Completed

• Conditions: Healthy
• Interventions: Dietary Supplement: L-Homoarginine; Drug: Placebo

• Registration Number: NCT02675660
• Lead Sponsor: Universitätsklinikum Hamburg-Eppendorf

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

1. 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.

2. Study Duration One year

3. 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.

Study Timeline

• Study Start: 2014-04
• Primary Completion: 2015-04
• Study Completion: 2016-01
• Study First Submitted: 2016-01-13
• Study First Submitted QC: 2016-02-02
• Study First Posted: 2016-02-05
• Status Verified: 2016-09
• Last Update Submitted: 2016-09-06
• Last Update Posted: 2016-09-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

1. 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
2. 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
3. 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

1. Sitting blood pressure greater than 160/100 or less than 90/60 mm Hg
2. Sitting heart rate greater than 99 bpm or less than 50 beats per minute (bpm)
3. History of clinically significant hypotensive episodes or symptoms of fainting, dizziness, or light-headedness
4. Body Mass Index (BMI) greater than 32 or less than 16 at screening [BMI = Weight (kg) ÷ Height2 (m2)]
5. History or symptoms of cardiovascular disease, particularly coronary artery disease, arrhythmias,or congestive heart failure
6. History of significant central nervous system disease, including transient ischemic attack, stroke, seizure disorder, or behavioral disturbances

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
L-Homoarginine	L-Homoarginine	125 mg of L-homoarginine
Placebo	Placebo	placebo capsules

Primary Outcome Measures

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

Secondary Outcome Measures

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