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

• ClinicalTrials.gov Identifier: NCT02675660
• Recruitment Status: Completed
• First Posted: February 5, 2016
• Last Update Posted: September 8, 2016
• Sponsor: Universitätsklinikum Hamburg-Eppendorf
• Information provided by (Responsible Party): Universitätsklinikum Hamburg-Eppendorf

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Healthy	Dietary Supplement: L-Homoarginine; Drug: Placebo	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Basic Science
• Official Title: Study to Evaluate the Safety, Tolerability, Kinetics, and Dynamics of Single and Multiple Doses of an Oral Formulation of L-Homoarginine
• Study Start Date: April 2014
• Actual Primary Completion Date: April 2015
• Actual Study Completion Date: January 2016

Arms and Interventions

Arm	Intervention/treatment
Experimental: L-Homoarginine; 125 mg of L-homoarginine	Dietary Supplement: L-Homoarginine; 125 mg L-homoarginine once daily
Placebo Comparator: Placebo; placebo capsules	Drug: Placebo; placebo capsules once daily

Outcome Measures

Primary Outcome Measures :

1. Area under the plasma concentration versus time curve (AUC) [ Time Frame: 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 :

1. Peak plasma concentration (Cmax) [ Time Frame: 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.
2. Half life of plasma concentration (t1/2) [ Time Frame: 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.

Eligibility Criteria

• Ages Eligible for Study: 20 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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

Contacts and Locations

Sponsors and Collaborators

Universitätsklinikum Hamburg-Eppendorf

Investigators

• Principal Investigator: Rainer H Böger, Prof. Dr.; UHHamburg Eppendorf

More Information

Publications:

Atzler D, Schwedhelm E, Choe CU. L-homoarginine and cardiovascular disease. Curr Opin Clin Nutr Metab Care. 2015 Jan;18(1):83-8. doi: 10.1097/MCO.0000000000000123.

Atzler D, Schonhoff M, Cordts K, Ortland I, Hoppe J, Hummel FC, Gerloff C, Jaehde U, Jagodzinski A, Boger RH, Choe CU, Schwedhelm E. Oral supplementation with L-homoarginine in young volunteers. Br J Clin Pharmacol. 2016 Dec;82(6):1477-1485. doi: 10.1111/bcp.13068. Epub 2016 Sep 20.

• Responsible Party: Universitätsklinikum Hamburg-Eppendorf
• ClinicalTrials.gov Identifier: NCT02675660
• Other Study ID Numbers: Homoarginine-UKE-KP2012-01
• First Posted: February 5, 2016
• Last Update Posted: September 8, 2016
• Last Verified: September 2016

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Universitätsklinikum Hamburg-Eppendorf:

kinetic data; volunteers