L-ornithine-L-aspartate / Generic mfg. - LARVOL DELTA

L-ornithine-L-aspertate improves quality of life and ammonia levels but not microbiome dysbiosis in cirrhosis: results of a phase 4 study (EASL 2025) - "In a recent retrospective study, we showed that L-ornithine-L-aspartate (LOLA) was associated with less dysbiosis... LOLA improved vitality in patients with cirrhosis, a clinically relevant patient reported outcome parameter but did not alter gut microbiome composition and function and could not prevent cirrhosis associated muscle loss in the majority of the patients. LOLA may be a useful adjunct treatment to improve quality of life in cirrhosis and may prevent muscle loss in patients with elevated ammonia levels."

Dysbiosis • HEOR • P4 data • CNS Disorders • Fibrosis • Gastrointestinal Disorder • Hepatic Encephalopathy • Hepatology • Immunology • Inflammation • Inflammatory Bowel Disease • Liver Cirrhosis • Sarcopenia • FGF • IGF1

Hepatic Encephalopathy: Current Thoughts on Pathophysiology and Management. (PubMed, Curr Neurol Neurosci Rep) - "First protecting the liver and the brain from gut generated ammonia and other toxins by ensuring smooth bowel function and avoiding stagnation with the use of osmotic laxatives like lactulose or lactitol and also reducing the gut microbial load with use of anti-bacterials/bacteriophages like neomycin and rifaximin along with metronidazole...Currently L-ornithine L-aspartate (LOLA) is being used to reduce the ammonia load to the liver...Finally in resistant cases the use of liver transplant needs to be considered. Alternatively extracorporeal liver assist devices may be used like Molecular Adsorbent Recirculating System (MARS) or Single-Pass Albumin Dialysis (SPAD)."

Journal • Review • CNS Disorders • Hepatic Encephalopathy • Hepatitis C • Hepatology • Infectious Disease • Inflammation • Liver Failure • Movement Disorders • Parkinson's Disease • Psychiatry • Transplantation • IL17A • IL6 • TNFA

Arginine glutamate injection for the treatment of mild hepatic encephalopathy: an openlabel, randomized, controlled, non-inferiority trial (APASL 2025) - P4 | "Both arginine glutamate injection and L-ornithine-L-aspartate injection effectively alleviated clinical symptoms and reduced blood ammonia levels in patients with cirrhosis and mild HE, with the clinical improvement rate of arginine glutamate being non-inferior to that of L-ornithine-L-aspartate. Compared to L-ornithine-L-aspartate, arginine glutamate also achieved non-inferiority in reducing blood ammonia and improving number connection test scores, with no appreciable adverse effects.(ChiCTR2300068160) Table and Figure:Figure 1.Figure1. Primary outcome of clinical improvement of hepatic encephalopathy in the intention-to-treat and per-protocol population."

Clinical • Head-to-Head • CNS Disorders • Fibrosis • Gastrointestinal Disorder • Hepatic Encephalopathy • Hepatology • Immunology

Hepatic encephalopathy: risk identification and prophylaxis approaches. (PubMed, Metab Brain Dis) - "Traditional treatments such as lactulose and rifaximin remain the cornerstone of HE management, effectively reducing ammonia levels and preventing recurrence. However, novel approaches like L-ornithine L-aspartate, albumin infusions, and antioxidants like resveratrol show promise in further improving outcomes by addressing underlying pathophysiological mechanisms, including systemic inflammation and gut dysbiosis...The future of HE management lies in personalized medicine, targeting specific inflammatory and metabolic pathways, with the potential integration of genetic manipulation. Continued research is essential to refine these strategies, ultimately aiming to improve the prognosis and quality of life for cirrhotic patients at risk of HE."

Journal • Review • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Fibrosis • Hepatic Encephalopathy • Hepatology • Immunology • Inflammation • Liver Cirrhosis

Unusual Presentation of Confusion: Hyperammonaemic Hepatic Encephalopathy Due to Intrahepatic Portosystemic Venous Shunt. (PubMed, Ir Med J) - "Management included the commencement of Lactulose, Rifaximin, and L-ornithine L-aspartate (LOLA). Intrahepatic portosystemic venous shunts should be considered in the differential diagnosis of patients presenting with confusion or other unexplained neurological symptoms, especially in the presence of liver dysfunction. Early diagnosis and appropriate management are crucial for favourable outcomes."

Journal • CNS Disorders • Fatigue • Hepatic Encephalopathy • Hepatology • Liver Failure

LOLAbiome: Effect of L-ornithine-L-aspertate (LOLA) on the Gut Microbiome (clinicaltrials.gov) - P4 | N=55 | Active, not recruiting | Sponsor: Medical University of Graz | Recruiting ➔ Active, not recruiting

Enrollment closed • Fibrosis • Gastroenterology • Hepatology • Immunology • Liver Cirrhosis

Hepatic encephalopathy: experimental drugs in development and therapeutic potential. (PubMed, Expert Opin Investig Drugs) - "Standard therapies, including non-absorbable disaccharides and rifaximin, are widely used but show inconsistent efficacy. Alternatives such as polyethylene glycol and L-ornithine L-aspartate have been effective in certain cases...Additionally, the multifactorial nature of HE, together with a high spontaneous response rate, complicates efforts to isolate treatment effects. Despite current limitations, ongoing research and technological advances hold promise for more effective and individualized HE treatments in the future."

Clinical • Journal • Review • CNS Disorders • Hepatic Encephalopathy • Hepatology • Immune Modulation • Immunology • Inflammation • Transplantation

Efficacy of L-Ornithine L-Aspartate (LOLA) as an Adjunct to Branched Chain Amino Acids (BCAA) Enriched Solutions on Clinical Outcomes in ICU Patients With Hepatic Encephalopathy (clinicaltrials.gov) - P4 | N=140 | Completed | Sponsor: Ain Shams University | Recruiting ➔ Completed

Trial completion • CNS Disorders • Hepatic Encephalopathy • Hepatology

ARGININE GLUTAMATE INJECTION FOR THE TREATMENT OF MILD HEPATIC ENCEPHALOPATHY: AN OPEN LABEL, RANDOMIZED, CONTROLLED, NON-INFERIORITY TRIAL (AASLD 2024) - "Both arginine glutamate injection and L-ornithine-L-aspartate injection effectively alleviated clinical symptoms and reduced blood ammonia levels in patients with cirrhosis and mild HE, with the clinical improvement rate of arginine glutamate being non-inferior to that of L-ornithine-L-aspartate. Compared to L-ornithine-L-aspartate, arginine glutamate also achieved non-inferiority in reducing blood ammonia and improving number connection test scores, with no appreciable adverse effects."

Clinical • Head-to-Head • CNS Disorders • Fibrosis • Hepatic Encephalopathy • Hepatology • Immunology

Effects of L-Ornithine-L-Aspartate on Angiogenesis and Perfusion in Subacute Hind Limb Ischemia: Preliminary Study. (PubMed, Biomedicines) - "In conclusion, this study provides the first documented evidence of angiogenesis and perfusion recovery in the subacute phase of the HLI model following the administration of LOLA. With LOLA readily available on the commercial market, the implementation of LOLA treatment for PAD in humans can be expedited compared to other therapies still in the developmental stage."

Journal • Cardiovascular • Peripheral Arterial Disease • CD31 • PECAM1

Efficacy of L-Ornithine L-Aspartate (LOLA) as an Adjunct to Branched Chain Amino Acids (BCAA) Enriched Solutions on Clinical Outcomes in ICU Patients With Hepatic Encephalopathy (clinicaltrials.gov) - P4 | N=140 | Recruiting | Sponsor: Ain Shams University | Trial completion date: Jul 2024 ➔ Oct 2024 | Trial primary completion date: Jul 2024 ➔ Oct 2024

Trial completion date • Trial primary completion date • CNS Disorders • Hepatic Encephalopathy • Hepatology

L-ORNITHINE L-ASPARTATE(LOLA) VERSUS STANDARD MEDICAL THERAPY (SMT) FOR IMPROVEMENT OF SARCOPENIA IN PATIENTS WITH CIRRHOSIS - A RANDOMIZED OPEN LABEL TRIAL (UEGW 2024) - "Full abstracts will be published on 21 September 2024"

Clinical • Fibrosis • Hepatology • Immunology • Sarcopenia

Human Albumin Infusion in Liver Cirrhosis and Overt Hepatic Encephalopathy (HACHE) (clinicaltrials.gov) - P=N/A | N=174 | Not yet recruiting | Sponsor: General Hospital of Shenyang Military Region

New trial • CNS Disorders • Fibrosis • Gastroenterology • Hepatic Encephalopathy • Hepatology • Immunology • Liver Cirrhosis

From seizures to cognitive dysfunction: A case report of Fahr syndrome in an Afghan patient. (PubMed, Medicine (Baltimore)) - "This case underscores the importance of raising awareness among physicians, especially in areas with limited medical resources, about the significance of prompt diagnosis and appropriate symptomatic treatment in enhancing patient prognosis and quality of life."

Journal • CNS Disorders • Cognitive Disorders • Depression • Endocrine Disorders • Epilepsy • Hypoparathyroidism • Mental Retardation • Musculoskeletal Pain • Pain • Psychiatry • Renal Disease

Intravenous versus oral 'L-ornithine-L-aspartate' in overt hepatic encephalopathy: a randomized comparative study. (PubMed, Sci Rep) - "Hepatic encephalopathy (HE), a morbid ordeal affecting chronic liver disease patients always insists for the search of a rational, superior & infallible agent beyond the time-proven standards i.e., Lactulose & Rifaximin. HE grade & ammonia correlated positively in both groups. LOLA, regardless of administration route, has demonstrated efficacy in OHE."

Clinical • Journal • CNS Disorders • Hepatic Encephalopathy • Hepatology

l-Ornithine-l-Aspartate (LOLA) Normalizes Metabolic Parameters in Models of Steatosis, Insulin Resistance and Metabolic Syndrome. (PubMed, Pharmaceutics) - "We demonstrate for l-ornithine-l-aspartate a broad range of reconstituting effects on metabolic carriers and targets of catabolism/energy metabolism impaired in NAFLD. These findings strongly advocate further investigations to establish LOLA as a safe, efficacious, and cost-effective basic medication for preventing and/or alleviating NAFLD."

Journal • Addiction (Opioid and Alcohol) • CNS Disorders • Gastrointestinal Cancer • Hepatic Encephalopathy • Hepatoblastoma • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Oncology • Solid Tumor • ACACA • AMPK • CD36 • FASN • SCARB1

Efficacy of L-Ornithine L-Aspartate (LOLA) as an Adjunct to Branched Chain Amino Acids (BCAA) Enriched Solutions on Clinical Outcomes in ICU Patients With Hepatic Encephalopathy (clinicaltrials.gov) - P4 | N=140 | Recruiting | Sponsor: Ain Shams University | Trial completion date: Feb 2024 ➔ Jul 2024 | Trial primary completion date: Feb 2024 ➔ Jul 2024

Trial completion date • Trial primary completion date • CNS Disorders • Hepatic Encephalopathy • Hepatology

Pharmacologic Management of Hepatic Encephalopathy. (PubMed, Clin Liver Dis) - "In this article, we review the history, mechanism, and evidence for first-line pharmacologic therapies for hepatic encephalopathy including nonabsorbable disaccharides, antibiotics, and electrolyte management. We also review newer, second-line therapies including polyethylene glycol, albumin, branched-chain amino acids, probiotics and fecal microbiota transplant, zinc, and l-ornithine-l-aspartate."

Journal • Review • CNS Disorders • Fibrosis • Gastroenterology • Hepatic Encephalopathy • Hepatology • Immunology • Liver Cirrhosis • Transplantation

Prophylaxis of hepatic encephalopathy: current and future drug targets. (PubMed, Hepatol Int) - "Rifaximin is equally effective as lactulose in managing hepatic encephalopathy and is better tolerated...L-ornithine L-aspartate and probiotics are also useful in the management of hepatic encephalopathy...Nutritional therapy and fecal microbiota transplantation are newer therapies for hepatic encephalopathy but the evidences are limited, more research is required to prove their efficacy. Involvement of hospital pharmacists, telemedicine, and providing education are also beneficial in managing hepatic encephalopathy."

Journal • Review • CNS Disorders • Fibrosis • Hepatic Encephalopathy • Hepatitis C • Hepatology • Immunology • Liver Cirrhosis • Liver Failure • Psychiatry • Transplantation

LOLAbiome: Effect of L-ornithine-L-aspertate (LOLA) on the Gut Microbiome (clinicaltrials.gov) - P4 | N=55 | Recruiting | Sponsor: Medical University of Graz | Trial completion date: Jan 2025 ➔ Dec 2025 | Trial primary completion date: Feb 2024 ➔ Oct 2024

Trial completion date • Trial primary completion date • Fibrosis • Gastroenterology • Hepatology • Immunology • Liver Cirrhosis

Efficacy and Safety of Variable Treatment Options in the Prevention of Hepatic Encephalopathy: A Systematic Review and Network Meta-Analysis. (PubMed, Cureus) - "The results also demonstrated a significant reduction in ammonia between L-ornithine-L-aspartate (LOLA) and probiotics (MD= -19.17, 95% CI [-38.01; -0.32]), as well as a significant difference in the incidence of LOLA compared to placebo (MD= -22.62, 95% CI [-39.16; -6.07])...(Lactulose and Nitazoxanide) have the least adverse effects, followed by (Rifaximin and L-carnitine), then Probiotics. Yet, all mortality outcomes and quality of life changes yielded no useful findings. Future studies like RCTs must be done to compare our therapies directly."

Journal • Retrospective data • Review • CNS Disorders • Fibrosis • Gastroenterology • Hepatic Encephalopathy • Hepatology • Immunology • Liver Cirrhosis

Efficacy of L-ornithine L-aspartate for minimal hepatic encephalopathy in patients with cirrhosis: A meta-analysis of randomized controlled trials. (PubMed, Arab J Gastroenterol) - "LOLA has significant beneficial effects on reversal of MHE and prevention of OHE in patients with cirrhosis compared with placebo or no intervention."

Journal • Retrospective data • Review • CNS Disorders • Fibrosis • Hepatic Encephalopathy • Hepatology • Immunology

Safety of non-standard regimen of systemic steroid therapy in patients with Graves' orbitopathy: a single-centre experience. (PubMed, Pharmacol Rep) - "Active GO treatment with high-dose systemic GCs is not associated with serious side effects. Hyperglycemia is the most common steroid-induced complication."

Journal • Diabetes • Endocrine Disorders • Grave’s Disease • Immunology • Metabolic Disorders • Thyroid Eye Disease

Mild post-COVID syndrome in young patients (PubMed, Ter Arkh) - "An improvement in the objective findings, liver enzymes, a decrease in ammonia level, and an improvement in testing results for changes in cognitive functions were reported."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Developmental Disorders • Hepatic Encephalopathy • Hepatology • Infectious Disease • Liver Failure • Novel Coronavirus Disease • Respiratory Diseases

A Comprehensive Overview of the Past, Current, and Future Randomized Controlled Trials in Hepatic Encephalopathy. (PubMed, Medicina (Kaunas)) - "Despite recent interest in this condition, the effectiveness of secondary prophylaxis involving rixafimin, lactulose, or L-ornithine L-aspartate (LOLA) may be hindered by the unique microbial profiles each patient possesses. In terms of RCTs, otherwise found in distinct stages of development, n = 3 target FMT and n = 1 probiotics. Although we benefit from the necessary information and technology to design novel strategies for microbiota, only probiotics and synbiotics have been extensively studied in the last decade compared to FMT."

Journal • Review • CNS Disorders • Fibrosis • Hepatic Encephalopathy • Hepatology • Immunology • Transplantation