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

NCT ID: NCT02675660

Last Updated: 2016-09-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-04-30
• Study Completion Date: 2016-01-31

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.

Conditions

Healthy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: TRIPLE

Study Groups

L-Homoarginine

125 mg of L-homoarginine

Group Type: EXPERIMENTAL

L-Homoarginine

Intervention Type: DIETARY_SUPPLEMENT

125 mg L-homoarginine once daily

Placebo

placebo capsules

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

placebo capsules once daily

Interventions

L-Homoarginine

125 mg L-homoarginine once daily

Intervention Type: DIETARY_SUPPLEMENT

Placebo

placebo capsules once daily

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Universitätsklinikum Hamburg-Eppendorf

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Rainer H Böger, Prof. Dr.

Role: PRINCIPAL_INVESTIGATOR

UHHamburg Eppendorf

References

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.

Reference Type: BACKGROUND

PMID: 25474016 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 27434056 (View on PubMed)

Other Identifiers

Homoarginine-UKE-KP2012-01

Identifier Type: -

Identifier Source: org_study_id