Clinical trial NCT00312910: Probiotics for the Prevention of Major Complications of Cirrhosis
Official title: Probiotics for the Prevention of Major Complications of Cirrhosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Liver Cirrhosis
Keywords: Cirrhosis
Probiotics
Hepatic encephalopathy
Ammonia
Lead sponsor: Meir Medical Center
Sponsor class: OTHER
Collaborators: name: Ambrosia - SupHerb Ltd.
First posted: 2006-04-11
Enrollment: 50
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to determine whether probiotics are effective in the prevention of the complications of liver cirrhosis.

Detailed description: Colonic bacteria clearly play a major role in the pathogenesis of major complications in patients with liver cirrhosis. By producing ammonia and endotoxins they can cause hepatic encephalopathy , and their translocation from the gut to the peritoneal cavity is the major mechanism for spontaneous bacterial peritonitis. There are also new studies suggesting a possible connection between bacterial translocation and bleeding from esophageal varices. Some of the therapeutic measures for the treatment and prevention of complications in cirrhotic patients, such as antibiotics and lactulose, are partially directed against gut bacteria.

In recent years there is a growing interest in the effect of probiotic bacteria on gut flora and prevention of infection. They were found to prevent pediatric infectious diarrhea and antibiotic-associated diarrhea- especially those caused by Clostridium difficile.

The probiotic bacteria, among which the most common are the lactose fermenting Lactobacilli, inhibit the growth of pathogenic bacteria by acidifying the gut lumen, competing for nutrients, and by producing antimicrobial substances. They adhere to the gut mucosa and by that are thought to prevent bacterial translocation from the gut. These effects of probiotics raised the idea that they may have a role in the treatment and prevention of cirrhosis complications. A recent study examined the effect of probiotics on patients with minimal chronic hepatic encephalopathy. Hepatic encephalopathy was reversed in 50% of the patients receiving probiotics. These patients also demonstrated a significant reduction of blood levels of ammonia, bilirubin and ALT, and of pathologic bacteria in stool cultures. This study showed promising results but was carried out on a relatively small population. Furthermore, the effect of probiotics on the prevention of hepatic encephalopathy and other major complications of cirrhosis has not been studied yet. Therefore, more studies are needed to establish the role of probiotics in patients with cirrhosis.

Eligibility criteria: Inclusion Criteria:

Patients with liver cirrhosis with at least one of the followings

1)Major complication of cirrhosis in the past (including variceal bleeding, encephalopathy and SBP) 2)Evidence for portal hypertension 3)Reduced hepatic synthetic function

-

Exclusion Criteria:

1. Patients with alcoholic cirrhosis who still consume alcohol
2. Patients that are chronically treated with antibiotics or lactulose -

Primary outcomes:
measure: The effect of probiotics on the rate of complications of liver cirrhosis (variceal bleeding, hepatic encephalopathy, SBP)
Secondary outcomes:
measure: Hospital Admissions due to complications of cirrhosis
measure: Ammonia blood levels
measure: Hepatic and renal function
Other outcomes:
Locations:
city: Kfar-Sava
country: Israel
facility: Meir Medical Center
Study officials:
affiliation: Meir Medical Center, Kfar-Sava, Israel
name: David Pereg, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Meir Medical Center, Kfar-Sava, Israel
name: Yona Kitay-Cohen, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Liu Q, Duan ZP, Ha DK, Bengmark S, Kurtovic J, Riordan SM. Synbiotic modulation of gut flora: effect on minimal hepatic encephalopathy in patients with cirrhosis. Hepatology. 2004 May;39(5):1441-9. doi: 10.1002/hep.20194.
citation: Pereg D, Kimhi O, Tirosh A, Orr N, Kayouf R, Lishner M. The effect of fermented yogurt on the prevention of diarrhea in a healthy adult population. Am J Infect Control. 2005 Mar;33(2):122-5. doi: 10.1016/j.ajic.2004.11.001.
citation: Szajewska H, Kotowska M, Mrukowicz JZ, Armanska M, Mikolajczyk W. Efficacy of Lactobacillus GG in prevention of nosocomial diarrhea in infants. J Pediatr. 2001 Mar;138(3):361-5. doi: 10.1067/mpd.2001.111321.
citation: Pochapin M. The effect of probiotics on Clostridium difficile diarrhea. Am J Gastroenterol. 2000 Jan;95(1 Suppl):S11-3. doi: 10.1016/s0002-9270(99)00809-6.