Effects of Weight Loss on Portal Pressure in Patients With Overweight/Obesity and Cirrhosis

Obesity Clinical Trial

— SPORTDIET  

Official title:

Effects of Weight Loss on Portal Pressure in Patients With Compensated Cirrhosis and Overweight/Obesity

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01409356
• Other study ID #: SPORTDIET
• Status: Completed
• Phase: Phase 2
• First received: August 3, 2011
• Last updated: March 17, 2015
• Start date: October 2011
• Est. completion date: December 2014

Study information

• Verified date: March 2015
• Source: Hospital Clinic of Barcelona
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Comité Ético de Investigación Clínica
• Study type: Interventional

Clinical Trial Summary

Overweight/obesity is increasing both in the general population and in patients with cirrhosis. In compensated patients with cirrhosis increased BMI is a risk factor for clinical decompensation independent of liver function and portal pressure. Nonetheless, patients with cirrhosis and obesity show a progressive increase in portal pressure, which might explain their increased risk of complications. Since obesity is a potentially modifiable risk factor, we designed this proof-of-concept study to assess the effects of weight loss (obtained by 4 months of diet and exercise) on portal pressure in patients with compensated cirrhosis and overweight/obesity.

Description:

Overweight and obesity markedly increase the risk of appearance and progression of most chronic diseases, including chronic liver diseases. In the general population obesity is constantly and dramatically raising, and represents a global epidemics. In a study including both European and American patients, our group reported that in patients with compensated cirrhosis overweight/obesity is very frequently observed (55% OW, 15% OB in Spanish patients; > 50% OB in USA patients), being the figure similar to that of general population. Moreover, this study demonstrated that the increase in body mass index (BMI) is a risk factor for the development of decompensation of cirrhosis, independent of portal pressure and liver function (Berzigotti et al. Hepatology 2011). We also observed that included patients with cirrhosis and obesity showed a significant increase of portal pressure (estimated through hepatic venous pressure gradient measurement-HVPG), which was not found in OW or normal weight patients. This suggests that the mechanism inducing decompensation in obese patients with cirrhosis might be mediated by an increase in portal pressure, even if no data are available in this population to support this hypothesis. It is well known that in obesity the adipose tissue acquires a pro-inflammatory phenotype leading to increased release of IL-1, IL-6 and TNF-alfa and many other pro-fibrogenic cytokines and hormones, which might mediate also an increase in portal pressure.

Given these observation, and given the potential reversibility of OW/OB, we hypothesise that weight loss (obtained by diet and exercise) might effectively reduce the HVPG in patients with compensated cirrhosis and OW/OB, so reducing their risk to progression. We designed this proof-of-concept study to confirm this hypothesis.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: December 2014
• Est. primary completion date: February 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Age: 18-75 years

• Compensated liver cirrhosis (diagnosed by biopsy or clear clinical, laboratory and imaging data), of any etiology; patients who presented decompensation due to gastroesophageal variceal hemorrhage can also be included if hemorrhage a) occurred > 3 months before inclusion AND b) has been treated with drugs+band ligation AND c) no other decompensations occurred simultaneously.

• HVPG > 5 mmHg

• BMI > 26 Kg/m2

• Absence of gastroesophageal varices or small esophageal varices OR large varices only if the patient is already on treatment with beta-blockers since at least 6 weeks.

• In case of presence of systemic arterial hypertension and/or diabetes, patients can be included if the treatment of these condition is stable for at least 3 months

Exclusion Criteria:

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Compensated Cirrhosis
• Liver Cirrhosis
• Obesity

Intervention

Behavioral:
• Diet + exercise
Program of dietary counselling by dietists, who will periodically follow-up the patient to achieve weight loss; moreover a fitness professional will instruct and train the patients twice a week to enhance their physical activity. A step counter will be also given to all participants and daily step count will be recorded. The duration of diet+exercise is 4 months from baseline HVPG measurement.

Locations

Country	Name	City	State
Spain	Hospital Clinic	Barcelona
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	Hospital Vall D'Hebron	Barcelona
Spain	Hospital General Universitario Gregorio Marañón	Madrid
Spain	Hospital Puerta de Hierro	Madrid
Spain	Universitario Ramón y Cajal	Madrid

Sponsors (2)

Lead Sponsor	Collaborator
Hospital Clinic of Barcelona	Centro de Investigación Biomédica en Red

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	HVPG change	The effects of weight loss on portal pressure will be assessed by measuring the HVPG at baseline and after 4 months of diet+exercise in the included patients.	4 months	No
Secondary	Hepatic function	The effects of weight loss on liver function will be estimated by assessing standard liver tests and indocyanine green clearance at baseline and after 4 months of diet+exercise	4 months	Yes
Secondary	Serum markers of fibrosis, angiogenesis, endothelial dysfunction and oxidative stress	The effects of weight loss on Serum markers of fibrosis, angiogenesis, endothelial dysfunction and oxidative stress will be assessed by extracting adequate blood samples at baseline and after 4 months of diet+exercise	4 months	No
Secondary	Body adiposity changes	Changes in BMI and body fat% will be assessed by measuring body weight and % of fat at baseline and after 4 months of diet + exercise.	4 months	No