Probiotics for Portal Hypertension

NCT01134692 | Unknown Phase 3

• 1 other identifier: NG002
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Chronic peripheral and splanchnic vasodilatation are the hallmark hemodynamic abnormality in cirrhosis and contribute to the pathogenesis of portal hypertension. Alterations in intestinal motility and bacterial overgrowth in gut may predispose to the development of bacteraemia and endotoxaemia in cirrhotic patients which play a role in the hyperdynamic circulatory syndrome of cirrhosis. Probiotic therapy is aimed at changing the make-up of the indigenous microflora by administering specific strains of non-pathogenic and potentially beneficial microflora. In this study, the investigators hypothesize that a modification in the composition of the endogenous digestive microflora by oral bacteriotherapy with high potency probiotic preparations could be a safe way to regulate the portal pressure. As there is a relative paucity in effective pharmacological treatment for portal hypertension, these novel and innovative therapy might provide important alternative or adjunct therapy to beta blockers in the clinical management of patients with portal hypertension. Aims and objectives To study in patients with cirrhosis and large varices whether probiotics and/or norfloxacin given for 2 months :

1. 1.achieve a reduction in HVPG
2. 2.alter the endotoxin and cytokine levels, and improve systemic inflammatory responses
3. 3.well tolerated.
4. 4.Diagnosed cases of cirrhosis (by clinical, biochemical and radiological criteria with or without liver biopsy)
5. 5.No history of upper GI bleeding in the past
6. 6.Endoscopically documented large esophageal varices
7. 7.history of gastrointestinal bleeding
8. 8.patients who have received beta blockers for portal hypertension in the past 6 weeks.
9. 9.hepatic encephalopathy
10. 10.ongoing bacterial infection,
11. 11.Spontaneous bacterial peritonitis
12. 12.active alcoholism or illicit drug abuse
13. 13.alcoholic hepatitis
14. 14.Treatment with antibiotics in the preceding 2 weeks.
15. 15.presence of hepatocellular carcinoma,
16. 16.portal vein thrombosis
17. 17.serum creatinine\>1.5 mg/dL,
18. 18.treatment with vasoactive drugs in the past 6 weeks,
19. 19.history of arterial hypertension, congestive heart failure or arterial occlusive disease, and
20. 20.Refusal to participate.
21. 21.Active smokers.
22. 22.Group 1: Beta blockers + placebo
23. 23.Group 2: Beta blockers + Norfloxacin (400mg BD)
24. 24.Group 3: Beta blockers + probiotics. (one sachet of VSL#3 BD)
25. 25.Primary
26. 26.Secondary
27. 27.Change in digestive flora
28. 28.Reduction in serum and hepatic endotoxin and cytokine levels
29. 29.Assessment of improvement in the renal parameters and Systemic inflammatory response syndrome
30. 30.Improvement in the markers of oxidative injury
31. 31.Adverse effects

Conditions

Cirrhosis; Varices, Esophageal

Keywords

Patients with cirrhosis who have large esophageal varices with No history of upper GI bleeding in the past

Outcome Measures

Primary Outcomes (1)

• Change in HVPG levels as compared with baseline, to define responder (≥20% reduction in HVPG or ≤ 12 mm Hg).

  2 months

Secondary Outcomes (2)

• Assessment of improvement in the renal parameters and Systemic inflammatory response syndrome

  2 months

• Adverse effects

  2 months

Study Arms (3)

Propranolol + Placebo

PLACEBO COMPARATOR

Drug: Propranolol, Norfloxacin, VSL#3

Propranolol + Norfloxacin

ACTIVE COMPARATOR

drug

Drug: Propranolol, Norfloxacin, VSL#3

Propranolol + Probiotic

EXPERIMENTAL

VSL#3

Drug: Propranolol, Norfloxacin, VSL#3

Interventions

Propranolol, Norfloxacin, VSL#3 DRUG

Propranolol: as per heart rate titration Norfloxacin: 400mg BD

Propranolol + Norfloxacin; Propranolol + Placebo; Propranolol + Probiotic

Eligibility Criteria

• Age: 12 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Consecutive patients of cirrhosis with portal hypertension who fulfill the following criteria:
• Diagnosed cases of cirrhosis (by clinical, biochemical and radiological criteria with or without liver biopsy)
• No history of upper GI bleeding in the past
• Endoscopically documented large esophageal varices

You may not qualify if:

• history of gastrointestinal bleeding
• patients who have received beta blockers for portal hypertension in the past 6 weeks.
• hepatic encephalopathy
• ongoing bacterial infection,
• Spontaneous bacterial peritonitis
• active alcoholism or illicit drug abuse
• alcoholic hepatitis
• Treatment with antibiotics in the preceding 2 weeks.
• presence of hepatocellular carcinoma,
• portal vein thrombosis
• serum creatinine\>1.5 mg/dL,
• treatment with vasoactive drugs in the past 6 weeks,
• history of arterial hypertension, congestive heart failure or arterial occlusive disease, and
• Refusal to participate.
• Active smokers.

Sponsors & Collaborators

• Govind Ballabh Pant Hospital: lead

Study Sites (1)

GB Pant hospital

Delhi, National Capital Territory of Delhi, 110002, India

RECRUITING

MeSH Terms

Conditions

Fibrosis; Esophageal and Gastric Varices

Interventions

Propranolol; Norfloxacin

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Hypertension, Portal; Liver Diseases

Intervention Hierarchy (Ancestors)

Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Central Study Contacts

Nitin Gupta, MD

CONTACT

+919718599209; drnitingupta_id@rediffmail.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Masking: DOUBLE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV

Study Record Dates

• First Submitted: June 1, 2010
• First Posted: June 2, 2010
• Last Updated: June 2, 2010

Record last verified: 2010-05

Locations

IN (1)