Role of Nitric Oxide in Cirrhosis: Relationship With Systemic Hemodynamics, Renal Function, Vasoactive Systems and Endotoxemia
Summary
This study is to determine whether a compound, nitric oxide, made within the body, is the factor responsible for the changes in blood pressure and renal (kidney) functions that may occur during the course of cirrhosis. Patients with cirrhosis (liver scarring which causes poor liver function) will be eligible to participate. A group of healthy subjects will also be studied to compare the effects of the treatment to patients with cirrhosis and to confirm safety. A total number of 30 patients with cirrhosis and 10 healthy subjects will be enrolled in the study.
Description
Upon admission, the patients will be physically examined and started on a special diet that will continue throughout the study. During the first four days of the study, the weight, heart rate and blood pressure of the patients will be measured every morning and 24-hour urine will be collected. On day 5, intravenous lines will be inserted in the patient's arms. One line will be used to draw blood samples and the other line will be used to infuse medications. Blood samples will be taken to measure liver and kidney function, nitric oxide, and other hormones that participate in the regulation of body fluids and blood pressure. Inulin and paraaminohippurate infusions (substances used routinely in the study of kidney function) will be started and blood and urine samples will then be taken at periodic intervals. Ninety minutes after the initiation of inulin and PAH infusions, L-NMMA (an investigational drug expected to increase the blood pressure and improve the kidney functions) will be infused. Blood and urine samples will be collected every 30 minutes. These procedures will take 4 hours. A total amount of about 10 tablespoons of blood will be drawn during the study. The patients will be discharged from the GCRC the next morning and restarted on their regular medications.
Study Design
Masking: Open Label, Primary Purpose: Treatment
Conditions
Cirrhosis
Intervention
N-monomethyl-L-arginine
Location
4200 E. Ninth Ave., Box C281
Denver
Colorado
United States
80262
Status
Recruiting
Source
National Center for Research Resources (NCRR)
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT00005107
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
Liver Cirrhosis, Experimental
Experimentally induced chronic injuries to the parenchymal cells in the liver to achieve a model for LIVER CIRRHOSIS.
Arginine-trna Ligase
An enzyme that activates arginine with its specific transfer RNA. EC 6.1.1.19.
Liver Cirrhosis, Biliary
FIBROSIS of the hepatic parenchyma due to obstruction of BILE flow (CHOLESTASIS) in the intrahepatic or extrahepatic bile ducts (BILE DUCTS, INTRAHEPATIC; BILE DUCTS, EXTRAHEPATIC). Primary biliary cirrhosis involves the destruction of small intra-hepatic bile ducts and bile secretion. Secondary biliary cirrhosis is produced by prolonged obstruction of large intrahepatic or extrahepatic bile ducts from a variety of causes.
Arginine Kinase
An enzyme that catalyzes the phosphorylation of the guanidine nitrogen of arginine in the presence of ATP and a divalent cation with formation of phosphorylarginine and ADP. EC 2.7.3.3.
Picolines
A group of compounds that are monomethyl derivatives of pyridines. (From Dorland, 28th ed)
Clinical Trials
Phase 1 Study of L-NMMA in Patients With Liver Cirrhosis
Phase 1 study of the effects of nitric oxide inhibition with L-NMMA in patients with liver cirrhosis and healthy controls. It is hypothesized that nitric oxide availability is increased in...
L-NMMA Dose-response Study in Healthy Subjects
The purpose of this study is to investigate the effect of different levels of nitric oxide inhibition on blood pressure and arterial stiffness in healthy subjects. L-NMMA, an inhibitor of...
Arginine Malaria Trial: Study of Adjunctive Arginine in Falciparum Malaria
Acute falciparum malaria is associated with low plasma arginine and impaired nitric oxide (NO) production. Both are associated with poor outcome. This study will examine the safety and eff...
The Short Term Safety and Efficacy of Inhaled L-Arginine in Patients With Cystic Fibrosis
The objective of this trial is to determine the safety and effect on pulmonary function of 14 days of inhaled L-arginine versus placebo administered over a period of 14 days in a cohort of...
Prevention of Bleeding in Patient With Cirrhosis Undergoing Dental Extraction
The purpose of this study is to investigate how effective and cost saving 1-deamino-8-D-arginine vasopressin (desmopressin, DDAVP) is as opposed to the transfusion of blood products in pre...
PubMed Articles
In a continuing investigation into the pharmacophores and structure-activity relationship (SAR) of (3'R,4'R)-3',4'-di-O-(S)-camphanoyl-(+)-cis-khellactone (DCK) as a potent anti-HIV agent, 2'-monometh...
Arginine vasopressin (AVP) is the major physiological regulator of renal water excretion and blood volume. The AVP pathways of V(1a)R-mediated vasoconstriction and V(2)R-induced water retention repres...
The stability of the Alternaria mycotoxins alternariol, alternariol monomethyl ether, and altenuene upon bread baking was investigated by model experiments using a spiked wholemeal wheat flour matrix....
Transfer of arginine into lipid bilayers is nonadditive.
Computer simulations suggest that the translocation of arginine through the hydrocarbon core of a lipid membrane proceeds by the formation of a water-filled defect that keeps the arginine molecule hyd...
We report the first low-energy collisional-induced dissociation studies of the X(-)·arginine (X(-) = F(-), Cl(-), Br(-), I(-), NO(3)(-), ClO(3)(-)) series of clusters to investigate the novel phenome...
