Portal HypertensionPhase 2NCT05508633
The Instant Efficacy and Safety of Alverine in Decreasing Portal Hypertension: an Exploratory Pilot Study
A Phase 2 study testing Alverine Citrate in people with Portal Hypertension, run by Shanghai Changzheng Hospital at 1 site in China.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Portal Hypertension
- What is being tested?
- Alverine Citrate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteChina
- Study dates
- 28 Oct 2022to Dec 2025
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18-75 years.
- Confirmed evidence of cirrhosis/ Cirrhosis diagnosed by liver biopsy or by imaging studies showing a nodular liver, splenomegaly and/or collateral.
- Portal pressure greater than equal to (≥)10 mmHg.
- Signed informed consent.
Who cannot join
- Use of non-selective beta-blockers (e.g. carvedilol, propranolol) or statins within 1 month prior to dosing.
- Moderate or massive ascites, overt hepatic encephalopathy, gastrointestinal bleeding and other complications within 1 week.
- Previous splenectomy, cardia periesophageal vascular dissection, transjugular intrahepatic portosystemic shunt (TIPS), liver transplantation, etc.
- Coagulopathy, including platelet count < 50× 10^9/ L, international normalized ratio (INR) of prothrombin time ≥1.5.
- Serum total bilirubin ≥ 5 fold of upper limits of normal; serum sodium level < 125 mmol/ L; white blood cell count < 1× 10^9/ L.
- Severe chronic renal insufficiency (eGFR (CKD-EPI) < 20 ml/min/1.73 m2).
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- Presence of hepatic vein, portal vein, splenic vein thrombosis or cavernous transformation of the portal vein.
- Poorly controllable hypertension or diabetic patient; severe background disease like chronic respiratory failure, circulatory failure, kidney failure etc.
- Clinically diagnosed or suspected as malignancy, including hepatocellular carcinoma.
- Any uncontrolled active infection (e.g. lung infection, abdominal infection, HIV, etc) 4 weeks prior to enter in the study.
- Patient who are allergy to the experimental drug.
- Patients with abnormal mental symptoms or taking tricyclic antidepressants and similar drugs in the past 4 weeks.
- Gestation or lactation period women and women who plan to get pregnant during the study period.
- Patients who are participating other trials or have taken part in other in the past 4 weeks.
- Other situation where PI thinks the patient should be excluded.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site
Shanghai Changzheng hospital
Shanghai, Shanghai Municipality, 200001
About this study
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
Read the 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
- Being tested
- Alverine Citrate
- Keywords
- Portal hypertension, Alverine
- Medical subject headings
- Hypertension, Portal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Alverine CitrateDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Low dose Alverine | Experimental | Alverine 60mg (1 capsule), orally Receives: Drug: Alverine Citrate |
| High dose Alverine | Experimental | Alverine 120mg (2 capsules), orally Receives: Drug: Alverine Citrate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in portal pressure
Change in portal pressure from baseline to 2 hours after start of orally administration
Measured: Change in portal pressure from baseline to 2 hours after start of orally administration
Secondary outcomes (1)
Treatment response rate
The percentage of patients with portal pressure decreased by more than 10% fro baseline at 2h.
Measured: 2 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Aug 2022
- Study start28 Oct 2022
- Primary completionDec 2025 (estimated)
- Study completionDec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Portal HypertensionStudies of the same condition, open and under way.
- More trials run by Shanghai Changzheng HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shanghai Changzheng Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Wei-Fen Xie, Shanghai Changzheng Hospital
- Investigators
- Wei-Fen Xie, Principal investigator, Director of department of gastroenterology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05508633
- Sponsor's protocol ID
- CZXH2022002.01
- Status last verified
- Feb 2025
- First submitted
- 18 Aug 2022
- Last updated
- 25 Feb 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Instant Efficacy and Safety of Alverine in Decreasing Portal Hypertension: an Exploratory Pilot Study
- ClinicalTrials.gov ID
- NCT05508633
- Acronym / sponsor ID
- CZXH2022002.01
- Conditions
- Portal Hypertension
- Keywords
- Portal hypertension, Alverine
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Enrolling by invitation
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Shanghai Changzheng HospitalUniversity, hospital or other
- Study start
- 28 Oct 2022 (actual)
- Primary completion
- Dec 2025 (estimated)
- Study completion
- Dec 2025 (estimated)
- First posted
- 19 Aug 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Low dose Alverine | Experimental | Drug: Alverine CitrateAlverine 60mg (1 capsule), orally |
| High dose Alverine | Experimental | Drug: Alverine CitrateAlverine 120mg (2 capsules), orally |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Age 18-75 years.
- Confirmed evidence of cirrhosis/ Cirrhosis diagnosed by liver biopsy or by imaging studies showing a nodular liver, splenomegaly and/or collateral.
- Portal pressure greater than equal to (≥)10 mmHg.
- Signed informed consent.
Key exclusion criteria (15 listed)
- Use of non-selective beta-blockers (e.g. carvedilol, propranolol) or statins within 1 month prior to dosing.
- Moderate or massive ascites, overt hepatic encephalopathy, gastrointestinal bleeding and other complications within 1 week.
- Previous splenectomy, cardia periesophageal vascular dissection, transjugular intrahepatic portosystemic shunt (TIPS), liver transplantation, etc.
- Coagulopathy, including platelet count < 50× 10^9/ L, international normalized ratio (INR) of prothrombin time ≥1.5.
- Serum total bilirubin ≥ 5 fold of upper limits of normal; serum sodium level < 125 mmol/ L; white blood cell count < 1× 10^9/ L.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Alverine CitrateLow-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. | Drug | High dose Alverine, Low dose Alverine |
Primary outcome
Change in portal pressure
Time frame: Change in portal pressure from baseline to 2 hours after start of orally administration
Change in portal pressure from baseline to 2 hours after start of orally administration
1 secondary outcome
Treatment response rate
Time frame: 2 hours
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Feb 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Wei-Fen Xie principal investigator
Director of department of gastroenterology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Alverine Citrate in people with Portal Hypertension, run by Shanghai Changzheng Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: enrolling by invitation, as of the sponsor's last update on 25 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in portal pressure (time frame: Change in portal pressure from baseline to 2 hours after start of orally administration). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Feb 2025.