NCT06687265: Hyper-Met

Effects of Metformin on Hepatic Venous Pressure Gradient in Patients With Cirrhosis and Portal Hypertension

Recruiting now Phase 2 Last updated 13 April 2025

What this trial tests

Phase 2 trial testing Metformin in Cirrhosis in 76 participants. Currently enrolling.

Timeline

10 March 2025

Primary endpoint
30 March 2027

31 July 2027

Quick facts

Lead sponsor	Assistance Publique - Hôpitaux de Paris
Phase	Phase 2
Status	Recruiting now
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	triple
Primary purpose	treatment
Enrollment	76
Start date	10 March 2025
Primary completion	30 March 2027
Estimated completion	31 July 2027
Sites	1 location across France

Drugs / interventions tested

• Metformin (metformin) — full drug profile →
• Placebo

Conditions studied

• Cirrhosis — all drugs for Cirrhosis →
• Portal Hypertension Related to Cirrhosis — all drugs for Portal Hypertension Related to Cirrhosis →

Sponsor

Assistance Publique - Hôpitaux de Paris — full company profile →

Who can join

18 and older, any sex, with Cirrhosis or Portal Hypertension Related to Cirrhosis. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Portal hypertension (PHT) is defined by an elevated pressure gradient between the portal vein and the hepatic veins ≥ 5 mm Hg, and is the main vector of complications in cirrhosis.

When the hepatic venous pressure gradient (HVPG) is ≥ 10 mm Hg, it is considered as a " clinically significant PHT ": ascites and oesophageal varices (EV) may occur.

Above 12 mm Hg, there is a risk of variceal bleeding. Carvedilol, a non-selective beta-blocker (NSBB), is recommended in all the patients with cirrhosis and clinically significant PHT in order to prevent decompensation of cirrhosis.

Nevertheless, 40 % of patients are NSBB non-responders, i.e. they do not show a significant decrease in HVPG. In addition, NSBB responders treated for primary prophylaxis have an incidence of variceal bleeding of approximately 10% per year, with a six-week mortality of 20%. Therefore, there is an unmet need for PHT in patients with cirrhosis who do not respond to NSBB, and also for an increase in efficacy in responders. In a randomised pilot study, Rittig et al. observed a mean change in HVPG of -2,9 mm Hg in 16 patients with cirrhosis and HVPG ≥ 12 mm Hg, not treated with NSBB, 90 minutes after ingestion of 1000 mg metformin.

The study will be a prospective, national, multicentre, phase II, superiority comparative randomized (1:1) simple-blinded clinical trial with two parallel arms: metformin versus placebo.

The main objective is to evaluate the effect of metformin versus placebo during 28 days on HVPG, in patients with cirrhosis and a HVPG ≥ 12 mm Hg already treated with carvedilol.

Subjects randomized in the metformin group or placebo group will receive metformin ou placebo, one pill of 500 mg per os twice a day (one in the morning and one in the evening, during or at the end of the meal) for 28 days.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. From Pathophysiology to Practice: Evolving Pharmacological Therapies, Clinical Complications, and Pharmacogenetic Considerations in Portal Hypertension.
   Porada M, Bułdak Ł. · · 2025 · cited 5× · PMID 39997697 · DOI 10.3390/metabo15020072
2. Extracellular Vesicles: Orchestrators of Intrahepatic and Systemic Crosstalk in Metabolic Dysfunction-Associated Steatotic Liver Disease.
   Lei Y, Liu M, Tao X. · · 2026 · PMID 41599223 · DOI 10.3390/pharmaceutics18010116