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

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

Sponsors

Lead sponsor: Hospital Clinic of Barcelona

Collaborator: Consorcio Centro de Investigación Biomédica en Red, M.P.

Source Hospital Clinic of Barcelona
Brief 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.

Detailed 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.

Overall Status Completed
Start Date October 2011
Completion Date December 2014
Primary Completion Date February 2014
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
HVPG change 4 months
Secondary Outcome
Measure Time Frame
Hepatic function 4 months
Serum markers of fibrosis, angiogenesis, endothelial dysfunction and oxidative stress 4 months
Body adiposity changes 4 months
Enrollment 60
Condition
Intervention

Intervention type: Behavioral

Intervention name: Diet + exercise

Description: 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.

Arm group label: Diet+Exercise

Eligibility

Criteria:

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:

Gender: All

Minimum age: 18 Years

Maximum age: 75 Years

Healthy volunteers: No

Overall Official
Last Name Role Affiliation
Jaime Bosch, MD Principal Investigator Hospital Clinic and CIBERehd
Location
facility
Hospital Clinic | Barcelona, 08036, 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, Spain
Location Countries

Spain

Verification Date

March 2015

Responsible Party

Responsible party type: Principal Investigator

Investigator affiliation: Hospital Clinic of Barcelona

Investigator full name: Jaime Bosch

Investigator title: Prof.

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 1
Arm Group

Arm group label: Diet+Exercise

Arm group type: Experimental

Description: Program of weight loss through diet+exercise (=intervention)

Acronym SPORTDIET
Study Design Info

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov