NCT05508633

The Instant Efficacy and Safety of Alverine in Decreasing Portal Hypertension: an Exploratory Pilot Study

• Status: Enrolling By Invitation
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Sponsor: Shanghai Changzheng Hospital · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

The main purpose of this exploratory study was to investigate the instant efficacy and safety of alverine oral administration in decreasing portal hypertension. Condition of disease: Cirrhotic portal hypertension Intervention/treatment: Drug: Alverine 60 mg (1 capsule), orally Drug: Alverine 120 mg (2 capsules), orally

Detailed description

Portal hypertension is the main non-neoplastic consequence of chronic liver disease and represents the leading cause of death and liver transplantation in patients with liver cirrhosis. While no effective treatment has been addressed to cirrhosis, reduction of portal hypertension significantly prevents the complications of cirrhosis and then remarkedly improves patients' prognosis. At present, pharmacologic managements of portal hypertension recommended by guidelines are vasoactive modulators and nonselective β-blockers (NSBBs). Although these treatments are effective in reducing portal pressure in responsive patients, they are still far from ideal due to adverse events and unpredictable response. As the trends of death resulting from cirrhosis and portal hypertension remain high, the pathophysiology of portal hypertension needs to be further investigated, and novel therapeutic strategies for portal hypertension are needed urgently. Alverine citrate is an antispasmodic drug with specific action on the smooth muscle of the alimentary tract and uterus, and does not affect the heart, blood vessels, or tracheal muscle at therapeutic doses. It was used in conditions such as irritable bowel syndrome, painful diverticular disease of the colon and primary dysmenorrhea to relief the smooth muscle spasm. Alverine citrate has been reported as a selective antagonist of serotonin receptor 1A (HTR1A) that reduced the visceral pronociceptive effect of serotonin. We found that alverine had the therapeutic potential on portal hypertension by selectively antagonizing HTR1A in preclinical animal models. The trial aimed to evaluate the instant efficacy and safety of alverine oral administration in decreasing portal pressure of patients with cirrhotic portal hypertension. The trial was planned as a single center prospective randomized investigation evaluating two doses of alverine on instant portal pressure reduction in 20 subjects two hours after receiving either high dose (120 mg) or low dose (60 mg) of alverine. The primary outcome measurement is the change in portal pressure from baseline to 2 hours after start of orally administration. Alverine response rate and safety will be also evaluated.

Conditions

• Portal Hypertension

Interventions

Type	Name	Description
DRUG	Alverine Citrate	Low-dose group: Alverine (60 mg, 1 capsule) High-dose group: Alverine (120 mg, 2 capsules) The drug is orally given with 200 ml warm water after measurement of the baseline portal pressure.

Timeline

• Start date: 2022-10-28
• Primary completion: 2025-12-01
• Completion: 2025-12-01
• First posted: 2022-08-19
• Last updated: 2025-02-25

Locations

1 site across 1 country: China