Probiotics for Portal Hypertension

The recruitment status of this study is unknown because the information has not been verified recently.
Verified May 2010 by Govind Ballabh Pant Hospital.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
Govind Ballabh Pant Hospital
ClinicalTrials.gov Identifier:
NCT01134692
First received: June 1, 2010
Last updated: NA
Last verified: May 2010
History: No changes posted
  Purpose

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. achieve a reduction in HVPG
  2. alter the endotoxin and cytokine levels, and improve systemic inflammatory responses
  3. well tolerated.

Inclusion criteria:

Consecutive patients of cirrhosis with portal hypertension who fulfill the following criteria:

  1. Diagnosed cases of cirrhosis (by clinical, biochemical and radiological criteria with or without liver biopsy)
  2. No history of upper GI bleeding in the past
  3. Endoscopically documented large esophageal varices

Exclusion criteria

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

Study plan:

Ethical approval will be obtained prior to study initiation. Patients presenting to Department of Gastroenterology, GB Pant Hospital will be recruited in the study. Patients will be evaluated regarding the eligibility for the study. After being found eligible for the study, if the patient agrees to participate in the study, a signed informed consent will be obtained. Baseline HVPG will be measured in all patients and then they will be randomized into 3 groups:.

  1. Group 1: Beta blockers + placebo
  2. Group 2: Beta blockers + Norfloxacin (400mg BD)
  3. Group 3: Beta blockers + probiotics. (one sachet of VSL#3 BD)

30 patients will be enrolled into each group. The treatment will be continued for 2 months.

The study design is a randomized double-blinded placebo controlled trial.

Once patients have been enrolled, they will undergo baseline investigations. Blood will be drawn from both peripheral and hepatic veins and sent for routine parameters, pro-inflammatory cytokines (IL-1b, IL-6, IL-10, TNF-α, endotoxins, NO2 and NO3 levels, PRA, BNP). Samples will be stored at -70 ºC. Baseline vitals will be recorded.

Patients will be called at the end of 1 month for assessment of compliance and then at the end of the study (2 months) to repeat the HVPG and the same parameters as at the time of enrollment

End Points:

  1. Primary

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

  2. Secondary

    1. Change in digestive flora
    2. Reduction in serum and hepatic endotoxin and cytokine levels
    3. Assessment of improvement in the renal parameters and Systemic inflammatory response syndrome
    4. Improvement in the markers of oxidative injury
    5. Adverse effects

Condition Intervention Phase
Cirrhosis
Varices, Esophageal
Drug: Propranolol, Norfloxacin, VSL#3
Phase 3

Study Type: Interventional
Study Design: Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Prevention
Official Title: COMPARATIVE STUDY OF NORFLOXACIN AND PROBIOTICS ON PORTAL PRESSURE IN PATIENTS WITH CIRRHOSIS AND LARGE VARICES WHO HAVE NEVER BLED IN THE PAST

Resource links provided by NLM:


Further study details as provided by Govind Ballabh Pant Hospital:

Primary Outcome Measures:
  • Change in HVPG levels as compared with baseline, to define responder (≥20% reduction in HVPG or ≤ 12 mm Hg). [ Time Frame: 2 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Assessment of improvement in the renal parameters and Systemic inflammatory response syndrome [ Time Frame: 2 months ] [ Designated as safety issue: No ]
  • Adverse effects [ Time Frame: 2 months ] [ Designated as safety issue: Yes ]

Arms Assigned Interventions
Placebo Comparator: Propranolol + Placebo Drug: Propranolol, Norfloxacin, VSL#3
Propranolol: as per heart rate titration Norfloxacin: 400mg BD
Active Comparator: Propranolol + Norfloxacin
drug
Drug: Propranolol, Norfloxacin, VSL#3
Propranolol: as per heart rate titration Norfloxacin: 400mg BD
Experimental: Propranolol + Probiotic
VSL#3
Drug: Propranolol, Norfloxacin, VSL#3
Propranolol: as per heart rate titration Norfloxacin: 400mg BD

  Eligibility

Ages Eligible for Study:   12 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Consecutive patients of cirrhosis with portal hypertension who fulfill the following criteria:

  1. Diagnosed cases of cirrhosis (by clinical, biochemical and radiological criteria with or without liver biopsy)
  2. No history of upper GI bleeding in the past
  3. Endoscopically documented large esophageal varices

Exclusion Criteria:

  1. history of gastrointestinal bleeding
  2. patients who have received beta blockers for portal hypertension in the past 6 weeks.
  3. hepatic encephalopathy
  4. ongoing bacterial infection,
  5. Spontaneous bacterial peritonitis
  6. active alcoholism or illicit drug abuse
  7. alcoholic hepatitis
  8. Treatment with antibiotics in the preceding 2 weeks.
  9. presence of hepatocellular carcinoma,
  10. portal vein thrombosis
  11. serum creatinine>1.5 mg/dL,
  12. treatment with vasoactive drugs in the past 6 weeks,
  13. history of arterial hypertension, congestive heart failure or arterial occlusive disease, and
  14. Refusal to participate.
  15. Active smokers.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01134692

Contacts
Contact: Nitin Gupta, MD +919718599209 drnitingupta_id@rediffmail.com

Locations
India
GB Pant hospital Recruiting
Delhi, India, 110002
Contact: Nitin Gupta, MD    +919718599209    drnitingupta_id@rediffmail.com   
Sponsors and Collaborators
Govind Ballabh Pant Hospital
  More Information

No publications provided

Responsible Party: Nitin Gupta, G.B. Pant Hospital, Delhi
ClinicalTrials.gov Identifier: NCT01134692     History of Changes
Other Study ID Numbers: NG002
Study First Received: June 1, 2010
Last Updated: June 1, 2010
Health Authority: India: Ministry of Health

Keywords provided by Govind Ballabh Pant Hospital:
Patients with cirrhosis who have large esophageal varices with No history of upper GI bleeding in the past

Additional relevant MeSH terms:
Esophageal and Gastric Varices
Varicose Veins
Hypertension, Portal
Liver Cirrhosis
Fibrosis
Esophageal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Liver Diseases
Pathologic Processes
Vascular Diseases
Cardiovascular Diseases
Propranolol
Norfloxacin
Anti-Arrhythmia Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Antihypertensive Agents
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Vasodilator Agents
Enzyme Inhibitors
Nucleic Acid Synthesis Inhibitors
Anti-Bacterial Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on April 17, 2014