Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
RECRUITING
40 participants
OBSERVATIONAL
2023-07-15
2026-12-31
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
The main questions aims of this study are:
1. Compare the efficacy and safety of a therapeutic approach based on the administration of SGLT-2 inhibitors in addition to optimal medical therapy (MRA and loop diuretic) compared to traditional diuretic therapy only, in cirrhotic patients with saline retention and diabetes.
2. Demonstrate better control of the glycemic profile in cirrhotic diabetic patients using SGLT-2 inhibitors.
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
It is well-known that in liver cirrhosis the underlying pathogenetic events responsible of ascites are portal hypertension and splanchnic vasodilation. These mechanisms reduce the effective circulating blood volume, triggering counter-regulatory systems such as the sympathetic nervous system (SNS) and the renin-angiotensin-aldosterone system (RAAS), that leading to renal sodium and water retention.
Therefore, considering pathogenetic knowledge, the cornerstones of ascites treatment are sodium restriction and drugs such as mineralocorticoid receptor antagonists (MRA) and loop diuretics, reserving more invasive techniques, like paracentesis with administration of human albumin, for more severe patients with grade 3 ascites unresponsive to diuretics. However, even though diuretics have proven to be among the most efficient drugs in controlling ascites, patients with liver cirrhosis and ascites treated with diuretics develop adverse drug reactions in 20-40% of cases.
One of the most common comorbidities of liver cirrhosis is type-2 diabetes mellitus (DM2), which affects approximately one-third of cirrhotic patients. The connection between liver cirrhosis and DM2 is complex. DM2 can be a secondary effect or, conversely, a casual factor of liver dysfunction.
Sodium glucose cotransporter 2 inhibitors (SGLT-2i) are a relatively new class of drugs for the management of type-2 diabetes mellitus. They inhibit the reabsorption of sodium and glucose in the proximal convoluted tubule of the nephron, leading to a significant natriuresis and have proven to be effective and safe drugs for the control of the glycemic profile in patients with liver dysfunction.
In recently published case reports, SGLT-2i have also proven to be safe and effective in controlling the glycemic profile in patients with liver dysfunction. In these patients, in addition to better control the glycemic profile, they led to saline retention improvement and to weight loss, without inducing encephalopathy or acute kidney injury. Other studies have hypothesized that, similarly to the previously demonstrated beneficial effect of glyphozines in patients with acute heart failure, SGLT-2i may also lead to the improvement of complicated liver cirrhosis acting as "neuromodulators", suppressing the RAAS axis and inducing better mobilization of ascites and reduction of saline retention.
Currently, there are no randomized controlled trials supporting these evidences.
In this observational study the investigators intend to evaluate the efficacy and safety of SGLT-2i in cirrhotic and diabetic patients with saline retention.
Aims
* Comparing the efficacy and safety of a therapeutic approach based on the administration of SGLT-2i in addition to optimal medical therapy (MRA and loop diuretic) compared to traditional diuretic therapy only, in cirrhotic patients with saline retention and diabetes.
* Demonstrating better control of the glycemic profile in cirrhotic diabetic patients using SGLT-2i.
Sample and study design Our study will be a clinical, prospective, observational multicenter study. The investigators will enroll subjects with complicated liver cirrhosis and type II diabetes mellitus consecutively, in two centers: Internal Medicine Unit of the "Policlinico Paolo Giaccone", University Hospital of Palermo, Italy and Internal Medicine Unit of the "Ospedali Riuniti Villa Sofia- Cervello" Hospital of Palermo, Italy.
Sample size The sample size is difficult to determine as there are no studies that have evaluated the efficacy of SGLT-2i treatment in addition to diuretic therapy in the patient with liver cirrhosis and saline retention. To date, there are only a few case reports in the literature that have demonstrated its effectiveness. Considering the prospective and pilot nature of this study the investigators decided to enroll at least 40 patients.
Study design and outcome evaluation Our project has been approved by the ethics committee of the University Hospital of Palermo.
Patients enrolled on the basis of the inclusion and exclusion criteria and who agreed to enter the study, after signing the informed consent, will be assigned to intervention group (group A) or control group (group B).
Patients belonging to the intervention group (A) will be given SGLT-2 inhibitors, according diabetology indications, in addition to standard medical therapy for 6 months; the patients of the control group (B) will instead continue with the only standard medical therapy for 6 months, according diabetology indications.
Standard medical therapy will include dietary sodium restriction, treatment with diuretics (furosemide and spironolactone), hypoglycemic therapy (metformin, insulin, or both) and other supportive care. Patients taking non-selective beta-blockers will continue to do.
Patients in group A and group B will be evaluated for specific clinical and laboratory parameters before the start of the study (T0) and they will subsequently be evaluated again at 4 weeks, 3 months and 6 months (T1, T2, T3).
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Keywords
Explore important study keywords that can help with search, categorization, and topic discovery.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
CASE_CONTROL
PROSPECTIVE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
SGLT-2i Group
Patients diagnosed with Child-Turcotte-Pugh A6-B9 class Hepatic Cirrhosis (moderately impaired liver function) and type 2 Diabetes Mellitus assigned to start SGLT-2 inhibitors intake, according diabetology indications, in addition to standard medical therapy for 6 months.
SGLT2 inhibitor
Start of SGLT-2 inhibitors to treat diabetes according diabetology indications.
Standard Therapy Group
Patients diagnosed with Child-Turcotte-Pugh A6-B9 class Hepatic Cirrhosis (moderately impaired liver function) and type 2 Diabetes Mellitus assigned to continue standard medical therapy, according diabetology indications, for 6 months.
No interventions assigned to this group
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
SGLT2 inhibitor
Start of SGLT-2 inhibitors to treat diabetes according diabetology indications.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* Patients diagnosed with Child-Turcotte-Pugh A6-B class Hepatic Cirrhosis (moderately impaired liver function)
* Patients diagnosed with Hepatic Cirrhosis of viral etiology (if previous hepatitis C virus (HCV) infection they must be in Sustained Virological Response (SVR); if previous hepatitis B virus (HBV) infection they must have undetectable viral genome)
* Patients diagnosed with hepatic cirrhosis of metabolic etiology
* Patients diagnosed with liver cirrhosis of alcoholic etiology (non active potus)
* Patients with grade 1 ascites: ascites detectable only ultrasound that can be fully mobilized or controlled with diuretic therapy associated with or without moderate dietary sodium restriction
* Grade 2 ascites: ascites that leads to a moderate abdominal distension and that recurs on at least 3 occasions within a 12-month period despite sodium restriction and adequate diuretic therapy (23)
* Patients diagnosed with type II diabetes mellitus defined according to 2022 American Diabetes Association (ADA) guidelines.
Exclusion Criteria
* Ascites of non-cirrhotic origin
* Patients diagnosed with heart failure Heart (NYHA) class =\> 2
* Patients diagnosed with acute renal failure
* Patients diagnosed with chronic renal failure and glomerular filtration rate (eGFR) below 25ml/min
* Patients with hepatocellular carcinoma (diagnosed according to the Barcelona criteria) or other active tumors (25)
* Grade 3 ascites: ascites that causes marked distention of the abdomen and that cannot be mobilized or whose early recurrence (i.e. after large volume paracentesis) cannot be satisfactorily prevented by medical therapy
* Patients diagnosed with acute Spontaneous Bacterial Peritonitis (26)
* Patients diagnosed with severe hepatic encephalopathy
* Patients diagnosed with autoimmune diseases on active steroid treatment
* Patients diagnosed with liver cirrhosis due to storage diseases
* Patients diagnosed with cirrhosis of the liver due to enzyme deficiency
* Patients diagnosed with complete portal thrombosis
* Patients with active sepsis
* Pregnant or breastfeeding women
* Patients who use drugs
* Patients with active alcohol consumption
18 Years
80 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Azienda Ospedaliera Ospedali Riuniti Villa Sofia Cervello
OTHER
University of Palermo
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Aurelio Seidita
Medical Doctor
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Lydia Giannitrapani, MD
Role: PRINCIPAL_INVESTIGATOR
University of Palermo
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Internal Medicine Unit, V. Cervello Hospital
Palermo, Italy, Italy
Department of Internal Medicine, University Hospital of Palermo
Palermo, Palermo, Italy
Countries
Review the countries where the study has at least one active or historical site.
Central Contacts
Reach out to these primary contacts for questions about participation or study logistics.
Facility Contacts
Find local site contact details for specific facilities participating in the trial.
Aurelio Seidita, MD
Role: primary
Francesca Mandreucci, MD
Role: backup
Aurelio Seidita, MD
Role: backup
Antonio Carroccio, MD
Role: backup
Salvatore Madonia, MD
Role: backup
Francesca Mandreucci, MD
Role: backup
Giuseppe Malizia, MD
Role: backup
Andrea Affronti, MD
Role: backup
Fabrizio Bronte, MD
Role: backup
Lydia Giannitrapani, MD
Role: primary
Maurizio Soresi, MD
Role: backup
Lydia Giannitrapani, MD
Role: backup
Maurizio Soresi, MD
Role: backup
Anna Licata, MD
Role: backup
Roberto Citarrella, MD
Role: backup
Mario Barbagallo, MD
Role: backup
Eleonora Santangelo, MD
Role: backup
Roberta Chianetta, MD
Role: backup
References
Explore related publications, articles, or registry entries linked to this study.
Bernardi M, Moreau R, Angeli P, Schnabl B, Arroyo V. Mechanisms of decompensation and organ failure in cirrhosis: From peripheral arterial vasodilation to systemic inflammation hypothesis. J Hepatol. 2015 Nov;63(5):1272-84. doi: 10.1016/j.jhep.2015.07.004. Epub 2015 Jul 17.
Angeli P, Gatta A, Caregaro L, Menon F, Sacerdoti D, Merkel C, Rondana M, de Toni R, Ruol A. Tubular site of renal sodium retention in ascitic liver cirrhosis evaluated by lithium clearance. Eur J Clin Invest. 1990 Feb;20(1):111-7. doi: 10.1111/j.1365-2362.1990.tb01800.x.
Santos J, Planas R, Pardo A, Durandez R, Cabre E, Morillas RM, Granada ML, Jimenez JA, Quintero E, Gassull MA. Spironolactone alone or in combination with furosemide in the treatment of moderate ascites in nonazotemic cirrhosis. A randomized comparative study of efficacy and safety. J Hepatol. 2003 Aug;39(2):187-92. doi: 10.1016/s0168-8278(03)00188-0.
Garcia-Compean D, Gonzalez-Gonzalez JA, Lavalle-Gonzalez FJ, Gonzalez-Moreno EI, Maldonado-Garza HJ, Villarreal-Perez JZ. The treatment of diabetes mellitus of patients with chronic liver disease. Ann Hepatol. 2015 Nov-Dec;14(6):780-8. doi: 10.5604/16652681.1171746.
Kasichayanula S, Liu X, Zhang W, Pfister M, LaCreta FP, Boulton DW. Influence of hepatic impairment on the pharmacokinetics and safety profile of dapagliflozin: an open-label, parallel-group, single-dose study. Clin Ther. 2011 Nov;33(11):1798-808. doi: 10.1016/j.clinthera.2011.09.011. Epub 2011 Oct 26.
Montalvo-Gordon I, Chi-Cervera LA, Garcia-Tsao G. Sodium-Glucose Cotransporter 2 Inhibitors Ameliorate Ascites and Peripheral Edema in Patients With Cirrhosis and Diabetes. Hepatology. 2020 Nov;72(5):1880-1882. doi: 10.1002/hep.31270. No abstract available.
Kalambokis GN, Tsiakas I, Filippas-Ntekuan S, Christaki M, Despotis G, Milionis H. Empagliflozin Eliminates Refractory Ascites and Hepatic Hydrothorax in a Patient With Primary Biliary Cirrhosis. Am J Gastroenterol. 2021 Mar 1;116(3):618-619. doi: 10.14309/ajg.0000000000000995. No abstract available.
Saffo S, Taddei T. SGLT2 inhibitors and cirrhosis: A unique perspective on the comanagement of diabetes mellitus and ascites. Clin Liver Dis (Hoboken). 2018 Jul 26;11(6):141-144. doi: 10.1002/cld.714. eCollection 2018 Jun. No abstract available.
Gao Y, Wei L, Zhang DD, Chen Y, Hou B. SGLT2 Inhibitors: A New Dawn for Recurrent/Refractory Cirrhotic Ascites. J Clin Transl Hepatol. 2021 Dec 28;9(6):795-797. doi: 10.14218/JCTH.2021.00418. Epub 2021 Nov 26. No abstract available.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
ASLG01
Identifier Type: -
Identifier Source: org_study_id