The Effectiveness of L-ornithine-L-aspartate (LOLA) on Plasma Ammonia in Cirrhotic Patients After TIPS

The Effectiveness of L-ornithine-L-aspartate on Plasma Ammonia in Cirrhotic Patients After TIPS Procedure: a Prospective, Randomized, Controlled, Open-label Clinical Trial

The aim of this study is to evaluate the effectiveness of L-ornithine-L-aspartate (LOLA) on plasma ammonia in cirrhotic patients after Transjugular Intrahepatic Portosystemic Shunt (TIPS) procedure.

Study Overview

• Status: Completed
• Conditions: Decompensated Cirrhosis; Portal Hypertension; Bleeding Varices; Refractory Ascites
• Intervention / Treatment: Drug: L-ornithine-L-aspartate

Detailed Description

Patients with successful TIPS deployment are randomized to LOLA arm and blank control arm. Plasma ammonia concentrations are measured before TIPS, day 1, day 4 and day 7 after TIPS.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• China
  • Shaanxi
    • Xi'an, Shaanxi, China, 710032
      • Xijing Hospital of Digestive Diseases, Fourth Military Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Cirrhotic patients with refractory ascites or at least one episode of variceal bleeding
• No active bleeding within 5 days before TIPS
• Child-Pugh score ≤ 11
• Signed written informed consent

Exclusion Criteria:

• An age < 18 years or > 65 years
• With TIPS contraindications
• Using drugs for hepatic encephalopathy such as neomycin, rifaximin, lactulose, lactitol or branched-chain amino acid.
• Intake of psychostimulants, sedatives, antidepressants, benzodiazepines or benzodiazepine-antagonists
• Past or present history of hepatic encephalopathy
• Pregnancy or breast-feeding
• Hepatic carcinoma and/or other malignancy diseases
• Sepsis
• Spontaneous bacterial peritonitis
• Uncontrollable hypertension
• Serious cardiac or pulmonary dysfunction
• Renal failure
• Portal vein thrombosis
• History of organ transplantation
• History of HIV (human immunodeficiency viruses) infection

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LOLA group; Intervention: LOLA (30g per day) for a week.	Drug: L-ornithine-L-aspartate; The patients will be treated with LOLA (30g per day) for a week after TIPS procedure.
No Intervention: Control group; Patients will not be treated with LOLA.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma ammonia	The plasma ammonia concentrations of venous blood at the first, fourth and seventh days after TIPS procedure.	One week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of hepatic encephalopathy		One week
Liver function	The liver function (includes PT/INR, APTT, albumin, bilirubin, Child-Pugh score) at the first, fourth and seventh days after TIPS procedure.	One week
Psychometric tests	The results of the psychometric tests (include number connection test A, number connection test B, digit symbol test, serial dotting test, line tracing test) at the first, fourth and seventh days after TIPS procedure.	One week

Collaborators and Investigators

• Sponsor: Air Force Military Medical University, China
• Investigators: Principal Investigator: Guohong Han, PhD & MD, Xijing Hospital of Digestive Diseases, Fourth Military Medical University

Publications and helpful links

General Publications

• Stauch S, Kircheis G, Adler G, Beckh K, Ditschuneit H, Gortelmeyer R, Hendricks R, Heuser A, Karoff C, Malfertheiner P, Mayer D, Rosch W, Steffens J. Oral L-ornithine-L-aspartate therapy of chronic hepatic encephalopathy: results of a placebo-controlled double-blind study. J Hepatol. 1998 May;28(5):856-64. doi: 10.1016/s0168-8278(98)80237-7.
• Rees CJ, Oppong K, Al Mardini H, Hudson M, Record CO. Effect of L-ornithine-L-aspartate on patients with and without TIPS undergoing glutamine challenge: a double blind, placebo controlled trial. Gut. 2000 Oct;47(4):571-4. doi: 10.1136/gut.47.4.571.
• Rose C, Michalak A, Rao KV, Quack G, Kircheis G, Butterworth RF. L-ornithine-L-aspartate lowers plasma and cerebrospinal fluid ammonia and prevents brain edema in rats with acute liver failure. Hepatology. 1999 Sep;30(3):636-40. doi: 10.1002/hep.510300311.
• Nolte W, Wiltfang J, Schindler C, Munke H, Unterberg K, Zumhasch U, Figulla HR, Werner G, Hartmann H, Ramadori G. Portosystemic hepatic encephalopathy after transjugular intrahepatic portosystemic shunt in patients with cirrhosis: clinical, laboratory, psychometric, and electroencephalographic investigations. Hepatology. 1998 Nov;28(5):1215-25. doi: 10.1002/hep.510280508.

Study record dates

Study Major Dates

• Study Start: December 1, 2011
• Primary Completion (Actual): December 1, 2012
• Study Completion (Actual): December 1, 2012

Study Registration Dates

• First Submitted: September 21, 2011
• First Submitted That Met QC Criteria: September 23, 2011
• First Posted (Estimate): September 27, 2011

Study Record Updates

• Last Update Posted (Estimate): December 19, 2012
• Last Update Submitted That Met QC Criteria: December 18, 2012
• Last Verified: December 1, 2012

More Information

Terms related to this study

• Keywords: Liver Cirrhosis; TIPS; Transjugular Intrahepatic Portosystemic Shunt; LOLA; L-ornithine-L-aspartate; Refractory Ascites
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Fibrosis; Ascites; Hypertension, Portal; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Excitatory Amino Acid Agents; Excitatory Amino Acid Agonists; N-Methylaspartate
• Other Study ID Numbers: LOLA-TIPS