UMIN-ICDS Clinical Trial
| Unique ID issued by UMIN | UMIN000063484 |
|---|---|
| Receipt number | R000072658 |
| Scientific Title | Serum interleukin-6 and neurocognitive responses to adjunctive probiotics in hepatic encephalopathy: a randomized placebo-controlled trial |
| Date of disclosure of the study information | 2026/10/31 |
| Last modified on | 2026/10/31 12:42:15 |
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Basic information
Public title
Effects of probiotics added to standard treatment on inflammation and cognitive function in patients with hepatic encephalopathy
Acronym
HE-PRO-IL6 Trial
Scientific Title
Serum interleukin-6 and neurocognitive responses to adjunctive probiotics in hepatic encephalopathy: a randomized placebo-controlled trial
Scientific Title:Acronym
HE-PRO-IL6 Trial
Region
| Asia(except Japan) |
Condition
Condition
Mild-to-moderate hepatic encephalopathy in patients with liver cirrhosis
Classification by specialty
| Hepato-biliary-pancreatic medicine |
Classification by malignancy
Others
Genomic information
NO
Objectives
Narrative objectives1
To evaluate the effect of eight weeks of adjunctive multistrain probiotic supplementation, compared with placebo, on serum interleukin-6 (IL-6) concentrations in patients with liver cirrhosis and mild-to-moderate hepatic encephalopathy receiving standard medical care. The study also assesses changes in neurocognitive function, including West Haven grades and Number Connection Test performance, and fecal pH.
Basic objectives2
Efficacy
Basic objectives -Others
Trial characteristics_1
Exploratory
Trial characteristics_2
Explanatory
Developmental phase
Not applicable
Assessment
Primary outcomes
Between-group difference in the change in serum interleukin-6 (IL-6) concentration (pg/mL) from baseline to 8 weeks after the initiation of treatment, measured using enzyme-linked immunosorbent assay (ELISA).
Key secondary outcomes
Changes from baseline to 8 weeks after the initiation of treatment in:
1. Number Connection Test A (NCT-A) completion time, measured in seconds.
2. Number Connection Test B (NCT-B) completion time, measured in seconds.
3. Number Connection Test error counts.
4. Hepatic encephalopathy severity assessed using the West Haven Criteria.
5. Fecal pH.
Base
Study type
Interventional
Study design
Basic design
Parallel
Randomization
Randomized
Randomization unit
Individual
Blinding
Double blind -all involved are blinded
Control
Placebo
Stratification
NO
Dynamic allocation
NO
Institution consideration
Institution is not considered as adjustment factor.
Blocking
YES
Concealment
Numbered container method
Intervention
No. of arms
2
Purpose of intervention
Treatment
Type of intervention
| Food |
Interventions/Control_1
Multistrain probiotic supplementation (recorded as Ryllus in the study manuscript), containing Lactobacillus plantarum, Bifidobacterium bifidum, and Streptococcus thermophilus, administered twice daily for 8 weeks in addition to standard medical care.
Interventions/Control_2
Matching placebo administered for 8 weeks in addition to standard medical care, using the same administration schedule as the probiotic group.
Interventions/Control_3
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10
Eligibility
Age-lower limit
| 18 | years-old | <= |
Age-upper limit
| Not applicable |
Gender
Male and Female
Key inclusion criteria
1. Adult patients.
2. Patients diagnosed with decompensated liver cirrhosis.
3. Patients with mild-to-moderate hepatic encephalopathy.
Key exclusion criteria
1. Recent use of antibiotics or probiotics.
2. Active malignancy.
3. Advanced renal failure.
4. Uncontrolled severe infection.
Target sample size
30
Research contact person
Name of lead principal investigator
| 1st name | Desy |
| Middle name | |
| Last name | Hariyanti |
Organization
Faculty of Medicine, Universitas Sriwijaya
Division name
Division of Gastroenterology and Hepatology, Department of Internal Medicine
Zip code
30126
Address
Jl. Dr. Mohd. Ali, RSMH Complex, KM 3, Palembang, South Sumatra 30126, Indonesia
TEL
0711-373438
hariyantidesy28127273@gmail.com
Public contact
Name of contact person
| 1st name | Desy |
| Middle name | |
| Last name | Hariyanti |
Organization
Faculty of Medicine, Universitas Sriwijaya
Division name
Division of Gastroenterology and Hepatology, Department of Internal Medicine
Zip code
30126
Address
Jl. Dr. Mohd. Ali, RSMH Complex, KM 3, Palembang, South Sumatra 30126, Indonesia
TEL
0711-373438
Homepage URL
hariyantidesy28127273@gmail.com
Sponsor or person
Institute
Faculty of Medicine, Universitas Sriwijaya
Institute
Department
Personal name
Funding Source
Organization
None
Organization
Division
Category of Funding Organization
Self funding
Nationality of Funding Organization
Indonesia
Other related organizations
Co-sponsor
Name of secondary funder(s)
IRB Contact (For public release)
Organization
Health Research Ethics Committee, Dr. Mohammad Hoesin General Hospital, Palembang
Address
Jl. Jenderal Sudirman KM 3.5, Palembang, South Sumatra 30126, Indonesia
Tel
0711-354088
crursmh@gmail.com
Secondary IDs
Secondary IDs
NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW
Institutions
Institutions
Dr. Mohammad Hoesin General Hospital (Palembang, South Sumatra, Indonesia)
Other administrative information
Date of disclosure of the study information
| 2026 | Year | 10 | Month | 31 | Day |
Related information
URL releasing protocol
Publication of results
Unpublished
Result
URL related to results and publications
Number of participants that the trial has enrolled
30
Results
Thirty patients were randomized (15 per group); 26 completed 8-week follow-up (12 probiotics; 14 placebo). Median IL-6 changes were -1.09 and -0.75 pg/mL, respectively (between-group p=0.382). NCT-A changes were -76.5 vs -20 s (p=0.004), and NCT-B -120 vs -19.5 s (p=0.005). Fecal pH changes were not significantly different (p=0.051). These are complete-case results.
Results date posted
| 2026 | Year | 10 | Month | 31 | Day |
Results Delayed
Results Delay Reason
Date of the first journal publication of results
Baseline Characteristics
Baseline characteristics were available for 26 participants who completed follow-up (12 in the probiotic group and 14 in the placebo group). Overall, 20 participants (76.9%) were male. The probiotic group included 9 males (75.0%), with a mean age of 53.67 +/- 9.74 years; the placebo group included 11 males (78.6%), with a mean age of 52.43 +/- 10.90 years. Child-Pugh classes A/B were 8/4 in the probiotic group and 7/7 in the placebo group. Baseline median serum IL-6 concentrations were 3.17 and 3.38 pg/mL, respectively.
Participant flow
Fifty patients were assessed for eligibility; 20 were excluded or declined participation. Thirty participants were randomized equally to the probiotic group (n=15) or placebo group (n=15). During the eight-week follow-up, three participants in the probiotic group and one in the placebo group discontinued the study. Three discontinuations were associated with adverse events, and one participant died; group-specific attribution of these events was not documented. Twenty-six participants completed follow-up and were included in the final complete-case analysis (12 probiotics and 14 placebo). Paired fecal pH measurements were available for 23 participants.
Adverse events
During the eight-week intervention, nausea was reported on 6/12 participants in the probiotic group and 6/14 in the placebo group among study completers. Vomiting occurred in 2/12 and 1/14 participants, respectively. Among the 30 randomized participants, three discontinued follow-up in association with adverse events, and one participant died. Detailed information on the discontinuations and causal attribution to the interventions was insufficient. Therefore, the available safety data do not permit a comprehensive assessment of adverse events among all randomized participants.
Outcome measures
Primary outcome (serum IL-6): The median change from baseline to week 8 was -1.09 pg/mL (range -2.91 to 1.25) in the probiotic group and -0.75 pg/mL (range -3.37 to 2.34) in the placebo group. The between-group difference was not statistically significant (p=0.382). A significant within-group reduction was observed in the probiotic group (p=0.041).
Secondary outcomes: Median changes in NCT-A completion time were -76.5 seconds versus -20 seconds (p=0.004), while NCT-B changes were -120 versus -19.5 seconds (p=0.005), favoring the probiotic group. NCT error count changes were -1 versus -0.5 (p=0.782). The number of participants classified as having minimal hepatic encephalopathy increased from 4/12 to 11/12 in the probiotic group, while remaining at 9/14 in the placebo group; no direct between-group comparison of West Haven transitions was available. Median fecal pH changes were -1.0 (n=11) versus 0.0 (n=12), respectively (p=0.051). Analyses were based on study completers.
Plan to share IPD
Undecided
IPD sharing Plan description
A decision regarding the sharing of de-identified individual participant data has not yet been made. The scope of data sharing, availability period, access criteria, and procedures remain to be determined.
Progress
Recruitment status
Completed
Date of protocol fixation
| 2025 | Year | 12 | Month | 15 | Day |
Date of IRB
| 2026 | Year | 01 | Month | 09 | Day |
Anticipated trial start date
| 2026 | Year | 02 | Month | 02 | Day |
Last follow-up date
| 2026 | Year | 07 | Month | 31 | Day |
Date of closure to data entry
| 2026 | Year | 08 | Month | 07 | Day |
Date trial data considered complete
| 2026 | Year | 08 | Month | 14 | Day |
Date analysis concluded
| 2026 | Year | 08 | Month | 28 | Day |
Other
Other related information
This trial was retrospectively registered in UMIN-CTR after participant enrollment and follow-up had been completed. The study was conducted at Dr. Mohammad Hoesin General Hospital, Palembang, Indonesia. Ethics approval was granted on January 9, 2026 (approval number: DP.04.03/D.XVIII.06.08/ETIK/009/2026).
Management information
Registered date
| 2026 | Year | 10 | Month | 31 | Day |
Last modified on
| 2026 | Year | 10 | Month | 31 | Day |
Link to view the page
Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000072658
