L-arginine Treatment in Mild Hypertension

NCT02894723 | Unknown Phase 4 DMC

• 1 other identifier: 0216-15-COM2
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Essential Hypertension is characterized by endothelial dysfunction due to reduced nitric oxide (NO) bioavailability. Impairment in nitric oxide-mediated vasodilatation in human brachial, coronary, and renal arteries has been demonstrated in patients with essential hypertension. Administration of L-arginine, a NO substrate yeld controversial results. The purpose of the present study, double blind and matched for age, sex and body mass index (BMI), is to assess the efficacy of L-arginine treatment on blood pressure (BP) control and arterial stiffness in patients with stage1 hypertension.

Conditions

Hypertension

Keywords

Hypertension,; Nitric Oxide; L-Arginine; Arterial Stiffness; Ambulatory blood pressure measurement

Outcome Measures

Primary Outcomes (1)

• Blood Pressure, mmHg

  change in systolic and/or diastolic blood pressure

  baseline [visit 0] to eight weeks

Secondary Outcomes (4)

• Central aortic BP, mmHg

  baseline (visit 0) to eight weeks

• Pulse pressure (mmHg)

  baseline (visit 0] to eight weeks

• Augmentation Index (%)

  baseline (visit 0] to eight weeks

• carotid femoral pulse wave velocity (m/s)

  baseline (visit 0] to eight weeks

Study Arms (2)

l-arginine

ACTIVE COMPARATOR

Patients will receive L-arginine 30 ml twice a day for 8 weeks.

Dietary Supplement: L-arginine

syrup

PLACEBO COMPARATOR

Patients will receive placebo, 30 ml twice a day for 8 weeks.

Dietary Supplement: syrup

Interventions

L-arginine DIETARY_SUPPLEMENT

30 ml arginoline contains 5 gr l-arginine

Also known as: Arginoline

l-arginine

syrup DIETARY_SUPPLEMENT

The same bottle of the experimental group, but without l-arginine

Also known as: placebo

syrup

Eligibility Criteria

• Age: 30 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Stage 1 hypertensive patients, with an office Systolic BP between 140-159 mmHg and/or a diastolic BP between 9-99 mmHg , untreated or treated with monotherapy.
• None to two risk factors \[smoking, hyperlipidemia, obesity , family history of cardiovascular disease\].
• BMI between 25 to 32.
• Twenty for hours ambulatory blood pressure monitor (ABPM) with a mean Systolic BP of 130-149 mmHg and/or a mean Diastolic BP of 80-89 mmHg.

You may not qualify if:

• Use of any drug that may affect nitric oxide synthesis and/or blood pressure values (nitrates, antihypertensive drugs, non steroidal anti-inflammatory drugs , steroids, pseudoephedrine).
• Diabetes mellitus.
• Renal failure defined as estimated glomerular filtration rate (eGFR) less than 60 ml/min, using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula.
• A previous diagnosis of ischemic heart disease, Transient ischemic attack (TIA), Stroke or peripheral arterial disease.
• Patients with recurrent herpes and women who are planning pregnancy during the next year.
• Cancer treated with radiotherapy or chemotherapy during the last year.

Sponsors & Collaborators

• Meir Medical Center: lead

Study Sites (1)

ADAM Institute of High Blood Pressure, Clalit Health Services

Herzliya, Hasharon Area, Israel

Location

Related Publications (20)

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• Li Q, Youn JY, Cai H. Mechanisms and consequences of endothelial nitric oxide synthase dysfunction in hypertension. J Hypertens. 2015 Jun;33(6):1128-36. doi: 10.1097/HJH.0000000000000587.

  PMID: 25882860 BACKGROUND

• Joannides R, Haefeli WE, Linder L, Richard V, Bakkali EH, Thuillez C, Luscher TF. Nitric oxide is responsible for flow-dependent dilatation of human peripheral conduit arteries in vivo. Circulation. 1995 Mar 1;91(5):1314-9. doi: 10.1161/01.cir.91.5.1314.

  PMID: 7867167 BACKGROUND

• Panza JA, Garcia CE, Kilcoyne CM, Quyyumi AA, Cannon RO 3rd. Impaired endothelium-dependent vasodilation in patients with essential hypertension. Evidence that nitric oxide abnormality is not localized to a single signal transduction pathway. Circulation. 1995 Mar 15;91(6):1732-8. doi: 10.1161/01.cir.91.6.1732.

  PMID: 7882481 BACKGROUND

• Treasure CB, Klein JL, Vita JA, Manoukian SV, Renwick GH, Selwyn AP, Ganz P, Alexander RW. Hypertension and left ventricular hypertrophy are associated with impaired endothelium-mediated relaxation in human coronary resistance vessels. Circulation. 1993 Jan;87(1):86-93. doi: 10.1161/01.cir.87.1.86.

  PMID: 8419028 BACKGROUND

• Higashi Y, Oshima T, Ozono R, Watanabe M, Matsuura H, Kajiyama G. Effects of L-arginine infusion on renal hemodynamics in patients with mild essential hypertension. Hypertension. 1995 Apr;25(4 Pt 2):898-902. doi: 10.1161/01.hyp.25.4.898.

  PMID: 7721451 BACKGROUND

• Taddei S, Virdis A, Mattei P, Ghiadoni L, Sudano I, Salvetti A. Defective L-arginine-nitric oxide pathway in offspring of essential hypertensive patients. Circulation. 1996 Sep 15;94(6):1298-303. doi: 10.1161/01.cir.94.6.1298.

  PMID: 8822983 BACKGROUND

• Schlaich MP, Parnell MM, Ahlers BA, Finch S, Marshall T, Zhang WZ, Kaye DM. Impaired L-arginine transport and endothelial function in hypertensive and genetically predisposed normotensive subjects. Circulation. 2004 Dec 14;110(24):3680-6. doi: 10.1161/01.CIR.0000149748.79945.52. Epub 2004 Nov 29.

  PMID: 15569830 BACKGROUND

• Forstermann U, Sessa WC. Nitric oxide synthases: regulation and function. Eur Heart J. 2012 Apr;33(7):829-37, 837a-837d. doi: 10.1093/eurheartj/ehr304. Epub 2011 Sep 1.

  PMID: 21890489 BACKGROUND

• Boger RH. Asymmetric dimethylarginine, an endogenous inhibitor of nitric oxide synthase, explains the "L-arginine paradox" and acts as a novel cardiovascular risk factor. J Nutr. 2004 Oct;134(10 Suppl):2842S-2847S; discussion 2853S. doi: 10.1093/jn/134.10.2842S.

  PMID: 15465797 BACKGROUND

• Naseem KM. The role of nitric oxide in cardiovascular diseases. Mol Aspects Med. 2005 Feb-Apr;26(1-2):33-65. doi: 10.1016/j.mam.2004.09.003. Epub 2005 Jan 24.

  PMID: 15722114 BACKGROUND

• Hishikawa K, Nakaki T, Suzuki H, Kato R, Saruta T. Role of L-arginine-nitric oxide pathway in hypertension. J Hypertens. 1993 Jun;11(6):639-45. doi: 10.1097/00004872-199306000-00008.

  PMID: 8397243 BACKGROUND

• Ast J, Cieslewicz AR, Korzeniowska K, Bogdanski P, Kazmierczak E, Olszewski J, Skoluda A, Jablecka A. Supplementation with L-arginine does not influence arterial blood pressure in healthy people: a randomized, double blind, trial. Eur Rev Med Pharmacol Sci. 2011 Dec;15(12):1375-84.

  PMID: 22288298 BACKGROUND

• Ast J, Jablecka A, Bogdanski P, Smolarek I, Krauss H, Chmara E. Evaluation of the antihypertensive effect of L-arginine supplementation in patients with mild hypertension assessed with ambulatory blood pressure monitoring. Med Sci Monit. 2010 May;16(5):CR266-71.

  PMID: 20424555 BACKGROUND

• Gui S, Jia J, Niu X, Bai Y, Zou H, Deng J, Zhou R. Arginine supplementation for improving maternal and neonatal outcomes in hypertensive disorder of pregnancy: a systematic review. J Renin Angiotensin Aldosterone Syst. 2014 Mar;15(1):88-96. doi: 10.1177/1470320313475910. Epub 2013 Feb 22.

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• Gallagher D, Adji A, O'Rourke MF. Validation of the transfer function technique for generating central from peripheral upper limb pressure waveform. Am J Hypertens. 2004 Nov;17(11 Pt 1):1059-67. doi: 10.1016/j.amjhyper.2004.05.027.

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• Butlin M, Qasem A, Avolio AP. Estimation of central aortic pressure waveform features derived from the brachial cuff volume displacement waveform. Annu Int Conf IEEE Eng Med Biol Soc. 2012;2012:2591-4. doi: 10.1109/EMBC.2012.6346494.

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• Davignon J, Ganz P. Role of endothelial dysfunction in atherosclerosis. Circulation. 2004 Jun 15;109(23 Suppl 1):III27-32. doi: 10.1161/01.CIR.0000131515.03336.f8.

  PMID: 15198963 RESULT

• Archer SL, Huang JM, Hampl V, Nelson DP, Shultz PJ, Weir EK. Nitric oxide and cGMP cause vasorelaxation by activation of a charybdotoxin-sensitive K channel by cGMP-dependent protein kinase. Proc Natl Acad Sci U S A. 1994 Aug 2;91(16):7583-7. doi: 10.1073/pnas.91.16.7583.

  PMID: 7519783 RESULT

• Podjarny E, Ben-Chetrit S, Rathaus M, Korzets Z, Green J, Katz B, Bernheim J. Pregnancy-induced hypertension in rats with adriamycin nephropathy is associated with an inadequate production of nitric oxide. Hypertension. 1997 Apr;29(4):986-91. doi: 10.1161/01.hyp.29.4.986.

  PMID: 9095088 RESULT

MeSH Terms

Conditions

Hypertension

Interventions

Arginine

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Amino Acids, Basic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Diamino; Amino Acids, Essential

Study Officials

• Eduardo Podjarny, MD

  Clalit Health Services

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Eduardo Podjarny, MD

CONTACT

0528339193; epodjarny@gmail.com

Naomi Nacasch, MD

CONTACT

0523815010; naomi.nacasch@clalit.org.il

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 15, 2016
• First Posted: September 9, 2016
• Study Start: September 1, 2016
• Primary Completion: February 1, 2017
• Study Completion: May 1, 2017
• Last Updated: September 9, 2016

Record last verified: 2016-06

Locations

IL (1)