Probiotics for Liver Cirrhosis With Portal Hypertension

• Sponsor: Po-Lin Chen, MD (Other)
• Overall Status: Completed
• CT.gov ID: NCT01598064
• Collaborator: Grape King Bio Ltd. (Industry)
• Enrollment: 49
• Location: 1
• Arms: 2
• Duration (Months): 16
• Patients Per Site Per Month: 3.1

Study Details

Study Description

Brief Summary

Recent studies indicate that probiotics can stimulate intestinal immunity and tighten the junctions of epithelial cells. By these ways, probiotics can reduce bacterial translocation; hence, they can ameliorate systemic inflammatory status. Because cirrhotic patients with portal hypertension often suffer from infections from intestinal flora, the investigators speculate that probiotics will be beneficial to those patients.

Condition or Disease	Intervention/Treatment	Phase
Liver Cirrhosis; Portal Hypertension	Dietary Supplement: GK#10; Drug: Placebo	N/A

Detailed Description

The investigators will recruit appropriate patients, 120 in number, randomly allocate into control and experimental arms. They will be given GK#10 or placebo for 8 weeks. Clinical parameters, such as liver function, renal function, and general conditions will be evaluated at specific time points, week 0, 5, 9, and 13 weeks. Primary outcome measurement will be survival and major complications analysis, and secondary outcome measurement will be liver function evaluation.

The investigators anticipate providing our sponsor with useful results about GK#10. The investigators will make clear the impacts from individual strains, the investigators will validate our speculation that probiotics do no harm to cirrhotic patients with portal hypertension, even be beneficial to them. If the investigators can validate the anticipation, patients can enjoy benefits from our study, and the probiotics may have the potential to sell to the patients in the world.

Study Design

• Study Type: Interventional
• Actual Enrollment: 49 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Clinical Trial of Probiotics in Preventing Complication Related to Portal Hypertension in Cirrhotic Patients
• Study Start Date: Apr 1, 2012
• Actual Primary Completion Date: Aug 1, 2013
• Actual Study Completion Date: Aug 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: GK#10 GK#10 1 pk tid for 8 weeks	Dietary Supplement: GK#10; GK#10, 1 pack tid; Other Names: Probiotics
Placebo Comparator: Placebo Placebo 1 pack tid for 8 weeks	Drug: Placebo; Placebo 1 pack tid po

Outcome Measures

Primary Outcome Measures

1. Admission Due to Complications Related to Portal Hypertension [8 weeks]

Secondary Outcome Measures

1. Liver Function Evaluation [8 weeks]

   Measure ALT level of patients

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Patients with history of complications related to liver cirrhosis, including hepatic encephalopathy, variceal bleeding, and spontaneous bacterial peritonitis

2. Patients with evidences of portal hypertension, such as hepatosplenomegaly, thrombocytopenia (< 100,000/ml)

Exclusion Criteria:

1. Active infection

2. Dialysis patients, myocardial infarction, life-threatening cardiac arrythmia and stroke

3. Hepatocellular carcinoma with life expectancy < 6 months

4. Portal vein thrombosis

5. in hepatic encephalopathy or liver function ALT > 3 x UNL, T-bilirubin > 4.0 mg/dL

6. GI tract bleeding in recent 1 weeks

7. Drug abuser

8. No informed consent

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	National Cheng Kung University Hospital	Tainan		Taiwan	70428

Sponsors and Collaborators

• Po-Lin Chen, MD
• Grape King Bio Ltd.

Investigators

• Principal Investigator: Xi-Zhang Lin, Professor

Study Documents (Full-Text)

None provided.

More Information

Publications

• De Minicis S, Brenner DA. NOX in liver fibrosis. Arch Biochem Biophys. 2007 Jun 15;462(2):266-72. Epub 2007 May 2. Review.
• Groszmann RJ. Hyperdynamic circulation of liver disease 40 years later: pathophysiology and clinical consequences. Hepatology. 1994 Nov;20(5):1359-63. Review.
• Guerrero Hernández I, Torre Delgadillo A, Vargas Vorackova F, Uribe M. Intestinal flora, probiotics, and cirrhosis. Ann Hepatol. 2008 Apr-Jun;7(2):120-4. Review.
• Johansson ML, Molin G, Jeppsson B, Nobaek S, Ahrné S, Bengmark S. Administration of different Lactobacillus strains in fermented oatmeal soup: in vivo colonization of human intestinal mucosa and effect on the indigenous flora. Appl Environ Microbiol. 1993 Jan;59(1):15-20.
• Salminen S, Salminen E. Lactulose, lactic acid bacteria, intestinal microecology and mucosal protection. Scand J Gastroenterol Suppl. 1997;222:45-8. doi: 10.1080/00365521.1997.11720717. Review.

• Responsible Party: Po-Lin Chen, MD, Doctor, National Cheng-Kung University Hospital
• ClinicalTrials.gov Identifier: NCT01598064
• Other Study ID Numbers: GK#10
• First Posted: May 15, 2012
• Last Update Posted: Sep 18, 2014
• Last Verified: Jul 1, 2014

• Additional relevant MeSH terms: Liver Cirrhosis; Hypertension, Portal; Hypertension; Fibrosis

Study Results

Participant Flow

Arm/Group Title	GK#10	Placebo
Arm/Group Description	GK#10 1 pk tid for 8 weeks	Placebo 1 pack tid for 8 weeks
Period Title: Overall Study
STARTED	25	24
COMPLETED	25	24
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	GK#10	Placebo	Total
Arm/Group Description	GK#10 1 pk tid for 8 weeks	Placebo 1 pack tid for 8 weeks	Total of all reporting groups
Overall Participants	25	24	49
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	59.9 (12)	58.9 (10.6)	59.4 (11.2)
Sex: Female, Male (Count of Participants)
Female	10 40%	7 29.2%	17 34.7%
Male	15 60%	17 70.8%	32 65.3%
Region of Enrollment (participants) [Number]
Taiwan	25 100%	24 100%	49 100%
Reasons of cirrhosis (participants) [Number]
CIRRHOSIS UNKNOWN REASONS	4 16%	3 12.5%	7 14.3%
CIRRHOSIS WITH REASONS	21 84%	21 87.5%	42 85.7%
Alcoholism (participants) [Number]
ALCOHOLSIM	2 8%	2 8.3%	4 8.2%
NON-ALCOHOLISM	23 92%	22 91.7%	45 91.8%
HBV (participants) [Number]
HBV	9 36%	11 45.8%	20 40.8%
NON-HBV	16 64%	13 54.2%	29 59.2%
HCV (participants) [Number]
HCV	8 32%	6 25%	14 28.6%
NON-HCV	17 68%	18 75%	35 71.4%
Ascites (participants) [Number]
ASCITES	9 36%	7 29.2%	16 32.7%
NO ASCITES	16 64%	17 70.8%	33 67.3%
Variceal bleeding (participants) [Number]
VARICEAL BLEEDING	0 0%	1 4.2%	1 2%
NO VARICEAL BLEEDING	25 100%	23 95.8%	48 98%
Hepatic encephalopathy (participants) [Number]
HEPATIC ENCEPHALOPATHY	2 8%	4 16.7%	6 12.2%
NO HEPATIC ENCEPHALOPATHY	23 92%	20 83.3%	43 87.8%
Diabetes (participants) [Number]
DIABETES	6 24%	6 25%	12 24.5%
NON DIABETES	19 76%	18 75%	37 75.5%
Hypertension (participants) [Number]
HYPERTENSION	4 16%	3 12.5%	7 14.3%
NON HYPERTENSION	21 84%	21 87.5%	42 85.7%
Cerebral vascular accident (participants) [Number]
CVA	0 0%	0 0%	0 0%
NON CVA	25 100%	24 100%	49 100%
WBC (cells/ml) (cells/ml) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cells/ml]	5019 (2027)	5116 (1815)	5111 (1886)
Hb (g/dL) (g/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [g/dL]	12.8 (1.8)	13.2 (2.1)	13.0 (2.0)
Platelet (x1000 platelets/μl) (x1000 platelets/uL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [x1000 platelets/uL]	108.3 (58.2)	112.3 (45.9)	110.2 (50.5)
Cr (mg/dL) (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	0.8 (0.3)	0.9 (0.2)	0.8 (0.3)
Total bilirubin (mg/dL) (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	1.2 (0.6)	1.2 (0.6)	1.2 (0.6)
AST (U/L) (U/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [U/L]	58.4 (24.8)	51.1 (20.9)	54.6 (22.5)
ALT (U/L) (U/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [U/L]	48.2 (29.3)	39.5 (21.3)	43.6 (25.0)
Prothrombin time (seconds) (seconds) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [seconds]	12.4 (1.1)	11.8 (1.5)	12.3 (1.3)
hsCRP (mg/L) (mg/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/L]	7.1 (0.5)	7.4 (1.3)	7.2 (0.9)
Malondialdehyde (μM) (μM) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [μM]	0.6 (0.2)	0.6 (0.2)	0.6 (0.2)
Re-admission (participants) [Number]
Re-admission	2 8%	3 12.5%	5 10.2%
No re-admission	23 92%	21 87.5%	44 89.8%
TNF-α (pg/mL) (pg/mL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [pg/mL]	12.0 (3.9)	10.8 (2.9)	11.4 (3.4)

Outcome Measures

1. Primary Outcome

Title	Admission Due to Complications Related to Portal Hypertension
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	GK#10	Placebo
Arm/Group Description	GK#10 1 pk tid for 8 weeks	Placebo 1 pack tid for 8 weeks
Measure Participants	25	24
Number [participants]	2 8%	3 12.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GK#10, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.25
	Comments
	Method	Chi-squared
	Comments

2. Secondary Outcome

Title	Liver Function Evaluation
Description	Measure ALT level of patients
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	GK#10: 8 Week	Placebo: 8 Week
Arm/Group Description	GK#10 1 pack three times per day for 8 weeks, and F/U ALT level.	Placebo 1 pack three times per day for 8 weeks, and F/U ALT level.
Measure Participants	16	19
Mean (Standard Deviation) [U/L]	48.9 (30.1)	39.2 (19.4)

Adverse Events

Time Frame	13 weeks
Arm/Group Title	GK#10		Placebo
Arm/Group Description	GK#10 1 pk tid for 8 weeks		Placebo 1 pack tid for 8 weeks
All Cause Mortality
	GK#10		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	GK#10		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/25 (0%)		0/24 (0%)
Other (Not Including Serious) Adverse Events
	GK#10		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/25 (0%)		0/24 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.