Effects of Weight Loss on Portal Pressure in Patients With Overweight/Obesity and Cirrhosis (SPORTDIET)
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Effects of Weight Loss on Portal Pressure in Patients With Compensated Cirrhosis and Overweight/Obesity|
- HVPG change [ Time Frame: 4 months ] [ Designated as safety issue: No ]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.
- Hepatic function [ Time Frame: 4 months ] [ Designated as safety issue: Yes ]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
- Serum markers of fibrosis, angiogenesis, endothelial dysfunction and oxidative stress [ Time Frame: 4 months ] [ Designated as safety issue: No ]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
- Body adiposity changes [ Time Frame: 4 months ] [ Designated as safety issue: No ]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.
|Study Start Date:||October 2011|
|Study Completion Date:||December 2014|
|Primary Completion Date:||February 2014 (Final data collection date for primary outcome measure)|
Program of weight loss through diet+exercise (=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.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01409356
|Barcelona, Spain, 08036|
|Hospital de la Santa Creu i Sant Pau|
|Hospital Vall D'Hebron|
|Hospital General Universitario Gregorio Marañón|
|Hospital Puerta de Hierro|
|Universitario Ramón y Cajal|
|Principal Investigator:||Jaime Bosch, MD||Hospital Clinic and CIBERehd|