Liver Cirrhosis, Portal Hypertension
Conditions
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.
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.
Interventions
DIETARY_SUPPLEMENTGK#10
GK#10, 1 pack tid
DRUGPlacebo
Placebo 1 pack tid po
Sponsors
Grape King Bio Ltd.
Po-Lin Chen, MD
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Admission Due to Complications Related to Portal Hypertension | 8 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Liver Function Evaluation | 8 weeks | Measure ALT level of patients |
Countries
Taiwan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| GK#10 GK#10 1 pk tid for 8 weeks | 25 |
| Placebo Placebo 1 pack tid for 8 weeks | 24 |
| Total | 49 |
Baseline characteristics
| Characteristic | Placebo | Total | GK#10 |
|---|---|---|---|
| Age, Continuous | 58.9 years STANDARD_DEVIATION 10.6 | 59.4 years STANDARD_DEVIATION 11.2 | 59.9 years STANDARD_DEVIATION 12 |
| Alcoholism ALCOHOLSIM | 2 participants | 4 participants | 2 participants |
| Alcoholism NON-ALCOHOLISM | 22 participants | 45 participants | 23 participants |
| ALT (U/L) | 39.5 U/L STANDARD_DEVIATION 21.3 | 43.6 U/L STANDARD_DEVIATION 25 | 48.2 U/L STANDARD_DEVIATION 29.3 |
| Ascites ASCITES | 7 participants | 16 participants | 9 participants |
| Ascites NO ASCITES | 17 participants | 33 participants | 16 participants |
| AST (U/L) | 51.1 U/L STANDARD_DEVIATION 20.9 | 54.6 U/L STANDARD_DEVIATION 22.5 | 58.4 U/L STANDARD_DEVIATION 24.8 |
| Cerebral vascular accident CVA | 0 participants | 0 participants | 0 participants |
| Cerebral vascular accident NON CVA | 24 participants | 49 participants | 25 participants |
| Cr (mg/dL) | 0.9 mg/dL STANDARD_DEVIATION 0.2 | 0.8 mg/dL STANDARD_DEVIATION 0.3 | 0.8 mg/dL STANDARD_DEVIATION 0.3 |
| Diabetes DIABETES | 6 participants | 12 participants | 6 participants |
| Diabetes NON DIABETES | 18 participants | 37 participants | 19 participants |
| Hb (g/dL) | 13.2 g/dL STANDARD_DEVIATION 2.1 | 13.0 g/dL STANDARD_DEVIATION 2 | 12.8 g/dL STANDARD_DEVIATION 1.8 |
| HBV HBV | 11 participants | 20 participants | 9 participants |
| HBV NON-HBV | 13 participants | 29 participants | 16 participants |
| HCV HCV | 6 participants | 14 participants | 8 participants |
| HCV NON-HCV | 18 participants | 35 participants | 17 participants |
| Hepatic encephalopathy HEPATIC ENCEPHALOPATHY | 4 participants | 6 participants | 2 participants |
| Hepatic encephalopathy NO HEPATIC ENCEPHALOPATHY | 20 participants | 43 participants | 23 participants |
| hsCRP (mg/L) | 7.4 mg/L STANDARD_DEVIATION 1.3 | 7.2 mg/L STANDARD_DEVIATION 0.9 | 7.1 mg/L STANDARD_DEVIATION 0.5 |
| Hypertension HYPERTENSION | 3 participants | 7 participants | 4 participants |
| Hypertension NON HYPERTENSION | 21 participants | 42 participants | 21 participants |
| Malondialdehyde (μM) | 0.6 μM STANDARD_DEVIATION 0.2 | 0.6 μM STANDARD_DEVIATION 0.2 | 0.6 μM STANDARD_DEVIATION 0.2 |
| Platelet (x1000 platelets/μl) | 112.3 x1000 platelets/uL STANDARD_DEVIATION 45.9 | 110.2 x1000 platelets/uL STANDARD_DEVIATION 50.5 | 108.3 x1000 platelets/uL STANDARD_DEVIATION 58.2 |
| Prothrombin time (seconds) | 11.8 seconds STANDARD_DEVIATION 1.5 | 12.3 seconds STANDARD_DEVIATION 1.3 | 12.4 seconds STANDARD_DEVIATION 1.1 |
| Re-admission No re-admission | 21 participants | 44 participants | 23 participants |
| Re-admission Re-admission | 3 participants | 5 participants | 2 participants |
| Reasons of cirrhosis CIRRHOSIS UNKNOWN REASONS | 3 participants | 7 participants | 4 participants |
| Reasons of cirrhosis CIRRHOSIS WITH REASONS | 21 participants | 42 participants | 21 participants |
| Region of Enrollment Taiwan | 24 participants | 49 participants | 25 participants |
| Sex: Female, Male Female | 7 Participants | 17 Participants | 10 Participants |
| Sex: Female, Male Male | 17 Participants | 32 Participants | 15 Participants |
| TNF-α (pg/mL) | 10.8 pg/mL STANDARD_DEVIATION 2.9 | 11.4 pg/mL STANDARD_DEVIATION 3.4 | 12.0 pg/mL STANDARD_DEVIATION 3.9 |
| Total bilirubin (mg/dL) | 1.2 mg/dL STANDARD_DEVIATION 0.6 | 1.2 mg/dL STANDARD_DEVIATION 0.6 | 1.2 mg/dL STANDARD_DEVIATION 0.6 |
| Variceal bleeding NO VARICEAL BLEEDING | 23 participants | 48 participants | 25 participants |
| Variceal bleeding VARICEAL BLEEDING | 1 participants | 1 participants | 0 participants |
| WBC (cells/ml) | 5116 cells/ml STANDARD_DEVIATION 1815 | 5111 cells/ml STANDARD_DEVIATION 1886 | 5019 cells/ml STANDARD_DEVIATION 2027 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 25 | 0 / 24 |
| serious Total, serious adverse events | 0 / 25 | 0 / 24 |
Outcome results
Primary
Admission Due to Complications Related to Portal Hypertension
Time frame: 8 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GK#10 | Admission Due to Complications Related to Portal Hypertension | 2 participants |
| Placebo | Admission Due to Complications Related to Portal Hypertension | 3 participants |
p-value: 0.25Chi-squared
Secondary
Liver Function Evaluation
Measure ALT level of patients
Time frame: 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GK#10 | Liver Function Evaluation | 48.9 U/L | Standard Deviation 30.1 |
| Placebo | Liver Function Evaluation | 39.2 U/L | Standard Deviation 19.4 |