Randomized Controlled Trial to Assess the Effects of Sapropterin on Hepatic and Systemic Hemodynamics in Patients With Liver Cirrhosis and Portal Hypertension

NCT01456286 | Completed Phase 2 DMC

• 1 other identifier: TEHYLIC
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to determine whether sapropterin (an oral analogue of tetrahydrobiopterin) could have a role in the treatment of portal hypertension secondary to liver cirrhosis. Sapropterin or placebo will be given for two weeks in patients with liver cirrhosis and clinically significant portal hypertension. Systemic and hepatic hemodynamics studies will be performed at baseline and after the intervention to assess the effect of sapropterin.

Conditions

Liver Cirrhosis; Portal Hypertension

Outcome Measures

Primary Outcomes (1)

• Changes in Hepatic Venous Pressure Gradient

  Changes in portal pressure gradient as measured by hepatic vein catheterization, induced by 2 week treatment with sapropterin/placebo

  2 weeks

Study Arms (2)

Sapropterin

EXPERIMENTAL

5 mg/kg daily first week; 10 mg/kg daily second week of treatment

Drug: sapropterin

placebo

PLACEBO COMPARATOR

Drug: sapropterin

Interventions

sapropterin DRUG

two weeks of treatment: 5 mg/kg per day during first week 10 mg/kg per day during second week

Sapropterin; placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Liver cirrhosis of any etiology diagnosed by biopsy or by clinical-imaging data
• Male or female patients between 18-75 years old in whom hepatic vein catheterization is indicated.
• Clinically significant portal hypertension defined by a HVPG ≥ 10 mmHg.
• Signed informed consent.

You may not qualify if:

• End-stage liver failure defined by one of the following: Prothrombin activity \< 40% and/or Bilirubin \> 5 mg/dl.
• Pregnancy or breastfeeding.
• Treatment with carvedilol or nitrates.
• Previous TIPS or derivative shunt.
• Hepatocellular carcinoma exceeding Milan criteria.
• Spontaneous bacterial peritonitis or any active infection when entering in the study.
• Portal vein thrombosis or cavernomatosis at ultrasound.
• Chronic heart failure, respiratory failure or chronic renal failure (Creatinine \>2 mg/dl).
• Previous convulsions or epilepsy.
• Hypersensibility to sapropterin or any of its excipients.

Sponsors & Collaborators

• Fundacion Clinic per a la Recerca Biomédica: lead

Study Sites (2)

Hospital Clínic de Barcelona

Barcelona, Barcelona, 08036, Spain

Location

Hospital Ramón y Cajal

Madrid, Madrid Community, 28034, Spain

Location

MeSH Terms

Conditions

Liver Cirrhosis; Hypertension, Portal

Interventions

sapropterin

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Juan C García-Pagán, MD phD

  Hospital Clínic of Barcelona

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Research Manager

Study Record Dates

• First Submitted: October 17, 2011
• First Posted: October 20, 2011
• Study Start: October 1, 2011
• Primary Completion: October 1, 2013
• Study Completion: October 1, 2013
• Last Updated: October 7, 2013

Record last verified: 2013-10

Locations

ES (2)