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

Primary Purpose

Portal Hypertension

Status
Not yet recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Alverine Citrate
Sponsored by
Shanghai Changzheng Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Portal Hypertension focused on measuring Portal hypertension, Alverine

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Age 18-75 years.
  2. Confirmed evidence of cirrhosis/ Cirrhosis diagnosed by liver biopsy or by imaging studies showing a nodular liver, splenomegaly and/or collateral.
  3. Portal pressure greater than equal to (≥)10 mmHg.
  4. Signed informed consent.

Exclusion Criteria:

  1. Use of non-selective beta-blockers (e.g. carvedilol, propranolol) or statins within 1 month prior to dosing.
  2. Moderate or massive ascites, overt hepatic encephalopathy, gastrointestinal bleeding and other complications within 1 week.
  3. Previous splenectomy, cardia periesophageal vascular dissection, transjugular intrahepatic portosystemic shunt (TIPS), liver transplantation, etc.
  4. Coagulopathy, including platelet count < 50× 10^9/ L, international normalized ratio (INR) of prothrombin time ≥1.5.
  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.
  6. Severe chronic renal insufficiency (eGFR (CKD-EPI) < 20 ml/min/1.73 m2).
  7. Presence of hepatic vein, portal vein, splenic vein thrombosis or cavernous transformation of the portal vein.
  8. Poorly controllable hypertension or diabetic patient; severe background disease like chronic respiratory failure, circulatory failure, kidney failure etc.
  9. Clinically diagnosed or suspected as malignancy, including hepatocellular carcinoma.
  10. Any uncontrolled active infection (e.g. lung infection, abdominal infection, HIV, etc) 4 weeks prior to enter in the study.
  11. Patient who are allergy to the experimental drug.
  12. Patients with abnormal mental symptoms or taking tricyclic antidepressants and similar drugs in the past 4 weeks.
  13. Gestation or lactation period women and women who plan to get pregnant during the study period.
  14. Patients who are participating other trials or have taken part in other in the past 4 weeks.
  15. Other situation where PI thinks the patient should be excluded.

Sites / Locations

  • Shanghai Changzheng hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Low dose Alverine

High dose Alverine

Arm Description

Alverine 60mg (1 capsule), orally

Alverine 120mg (2 capsules), orally

Outcomes

Primary Outcome Measures

Change in portal pressure
Change in portal pressure from baseline to 2 hours after start of orally administration

Secondary Outcome Measures

Treatment response rate
The percentage of patients with portal pressure decreased by more than 10% fro baseline at 2h.

Full Information

First Posted
August 18, 2022
Last Updated
August 18, 2022
Sponsor
Shanghai Changzheng Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT05508633
Brief Title
The Instant Efficacy and Safety of Alverine in Decreasing Portal Hypertension: an Exploratory Pilot Study
Official Title
The Instant Efficacy and Safety of Alverine in Decreasing Portal Hypertension: an Exploratory Pilot Study
Study Type
Interventional

2. Study Status

Record Verification Date
August 2022
Overall Recruitment Status
Not yet recruiting
Study Start Date
August 2022 (Anticipated)
Primary Completion Date
December 2022 (Anticipated)
Study Completion Date
December 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Shanghai Changzheng Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Portal Hypertension
Keywords
Portal hypertension, Alverine

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Low dose Alverine
Arm Type
Experimental
Arm Description
Alverine 60mg (1 capsule), orally
Arm Title
High dose Alverine
Arm Type
Experimental
Arm Description
Alverine 120mg (2 capsules), orally
Intervention Type
Drug
Intervention Name(s)
Alverine Citrate
Intervention Description
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.
Primary Outcome Measure Information:
Title
Change in portal pressure
Description
Change in portal pressure from baseline to 2 hours after start of orally administration
Time Frame
Change in portal pressure from baseline to 2 hours after start of orally administration
Secondary Outcome Measure Information:
Title
Treatment response rate
Description
The percentage of patients with portal pressure decreased by more than 10% fro baseline at 2h.
Time Frame
2 hours

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: 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). 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Chang-Peng Zhu
Phone
+86 13671547663
Email
zhuchangpeng@126.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Wei-Fen Xie
Organizational Affiliation
Director of department of gastroenterology
Official's Role
Principal Investigator
Facility Information:
Facility Name
Shanghai Changzheng hospital
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200001
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Chang-Peng Zhu
Phone
+86 13671547663
Email
zhuchangpeng@126.com

12. IPD Sharing Statement

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

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