L-arginine to Reduce Sympathetic Nerve Activity in CKD Patients

NCT03982160 | Recruiting Phase 4 DMC FDA Drug

• 1 other identifier: CKD-IRB-2016-0069
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 2

Brief Summary

Chronic kidney disease (CKD) is associated with a higher risk of cardiovascular disease and death. An overactive sympathetic nervous system in CKD patients is one of the major mechanisms increasing the cardiovascular risks in this patient population. A potential signal driving sympathetic nerve activity (SNA) involves accumulation of the endogenous nitric oxide synthase (NOS) inhibitor asymmetric dimethylarginine (ADMA). ADMA is elevated in CKD and is a strong, independent predictor of future cardiovascular events in these patients. . The goal of this study is to determine whether overcoming the accumulation of endogenous ADMA with acute L-arginine infusion reduces SNA in CKD patients.

Conditions

Chronic Kidney Disease

Keywords

L-arginine; blood pressure; ADMA

Outcome Measures

Primary Outcomes (1)

• Muscle sympathetic nerve activity (MSNA) will be reduced after L-arginine infusion

  Multiunit postganglionic MSNA will be recorded using standard microneurographic techniques. Briefly, a unipolar tungsten microelectrode will be inserted into muscle fascicles of the peroneal nerve near the fibular head of the right leg. Neural signals will be amplified, filtered (bandwidth, 700-2,000 Hz), rectified, and integrated (time constant, 0.1 s) to obtain mean voltage neurograms (University of Iowa Bioengineering, Iowa City, IA).

  30 minutes

Study Arms (2)

L-arginine

EXPERIMENTAL

Intravenous infusion of L-arginine (250-350 mg/kg) will be performed for 30 minutes.

Drug: L-Arginine

Saline

PLACEBO COMPARATOR

Saline will be infused for 30 minutes

Other: Placebo

Interventions

L-Arginine DRUG

Arginine Hydrochloride 60% concentration injection 15 g in 25 mL, contains arginine hydrochloride 600 mg/mL in water for injections to 25 mL.

L-arginine

Placebo OTHER

Saline

Saline

Eligibility Criteria

• Age: 35 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• CKD patients classified as Stage 3 and 4 of National Kidney Foundation Classification with estimated glomerular filtration rate (GFR) between 15 and 59 mL/min/1.73 m2 according to the Modification of Diet in Renal Disease (MDRD) formula based on serum creatinine, age, gender, and race.
• Men and women 35 to 75 years of age

You may not qualify if:

• myocardial infarction
• heart failure
• anemia (hemoglobin \<8 g/dl)
• cancer with current treatment
• previous organ transplantation
• immunosuppressant therapy
• human immunodeficiency virus infection
• pregnancy and/or lactating
• current tobacco use
• taking menopausal drugs (estradiol)
• treatment for diabetic neuropathy
• resting heart rate ≥ 100 bpm and
• systolic blood pressure ≤ 90 mmHg

Sponsors & Collaborators

• The University of Texas at Arlington: lead

Study Sites (2)

University of Delaware

Newark, Delaware, 19716, United States

RECRUITING

UT Southwestern

Dallas, Texas, 75390, United States

RECRUITING

MeSH Terms

Conditions

Renal Insufficiency, Chronic

Interventions

Arginine

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

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

Study Officials

• Paul J Fadel, PhD

  University of Texas at Arlington

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Paul J Fadel, PhD

CONTACT

8172724653; Paul.Fadel@uta.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Subjects will receive systemic intravenous infusion of L-arginine or saline for 30 minutes in a randomized order. The randomization will be carried out by research personnel.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: This will be a randomize, saline-controlled crossover design study

Study Record Dates

• First Submitted: June 6, 2019
• First Posted: June 11, 2019
• Study Start: February 1, 2018
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: March 3, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)