Clinical trial NCT06040814: Microbiota, Sarcopenia, and Hepatic Encephalopathy Change in Cirrhotic Patients Before and After Rehabilitation
Official title: To Explore the Changes of Fecal Microbiota Before and After Treatment in Patients With Liver Cirrhosis Complicated With Hepatic Encephalopathy or Sarcopenia as a Reference for Future Fecal Microbiota Transplantation
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Hepatic Encephalopathy
Keywords: Liver cirrhosis
Hepatic encephalopathy
Psychometric test
Sarcopenia
Fecal microbiota
Lead sponsor: Chang Gung Memorial Hospital
Sponsor class: OTHER
First posted: 2023-09-18
Enrollment: 120
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Through this plan, it will provide many benefits to patients with liver cirrhosis complicated with sarcopenia and/or hepatic encephalopathy, their family members, and the government in Taiwan:

1. To explore the changes of fecal microbiota before and after treatment such as resistance training rehabilitation in patients with liver cirrhosis complicated with sarcopenia and/or hepatic encephalopathy as a reference for future fecal microbiota transplantation;
2. To measure the changes of sarcopenia level before and after rehabilitation;
3. To measure the changes of hepatic encephalopathy level before and after rehabilitation.

These study results will certainly bring updated diagnostic tool, latest treatment options, avoid serious sequelae and reduce medical expenditure.

Detailed description: Chronic liver disease is notorious as Taiwan's national disease and more than 4,000 patients died of liver cirrhosis each year in Taiwan. Hepatic encephalopathy (HE) manifests from minimal HE (MHE) to overt HE (OHE). The diagnosis of covert HE (CHE) requires psychometric tests or neurophysiological tools. However, psychometric testing for patients with CHE is often neglected in Taiwan. On the basis of the capability to detect all forms of HE, further investigation on the association of HE with fecal microbiota alterations is urgently needed. It is because HE is associated with dysregulation in the gut-liver-brain axis, which includes intestinal barrier dysfunction and gut microbial dysbiosis. However, despite current standard of care (SOC) therapy i.e., lactulose and rifaximin, there remains a subset of patients who continue to suffer recurrence, which leads to further cognitive impairment, sarcopenia and readmissions. There remain several factors that can influence the microbiota, such as demographics (geographic area, sex and diet), etiology, drugs, interventions, and ﬁnally the sampling compartment. These factors need to be controlled for and considered in the interpretation of future studies. The microbiome dynamic change during rehabilitation in cirrhotic patients with sarcopenia has never been studied and is worth exploring.

Furthermore, from our previous study, the investigators have shown that one-year efficacy of rifaximin add-on to lactulose is superior to lactulose alone in patients with cirrhosis complicated with recurrent HE in Taiwan. The investigators also have preliminary data showing that rehabilitation could improve patient's sarcopenia. Further cohort validation is urgently required.

Our innovative research purposes:

1. To explore the changes of fecal microbiota before and after treatment such as resistance training rehabilitation as a reference for future fecal microbiota transplantation;
2. To measure the changes of sarcopenia levels before and after rehabilitation

Eligibility criteria: Inclusion Criteria:

* Patients with liver cirrhosis

Exclusion Criteria:

* unstable vital sign such as shock, coma or intubation status
* Non-curative hepatocellular carcinoma (cannot receive operation, radiofrequency ablation, liver transplantation,etc
* Un-curative malignancies
* Poor-controlled diabetes mellitus (HbA1C≧8)
* Active alcoholism (male alcohol ≧40g/day, or ≧140g/week; female ≧ 30g/day, or ≧70g/week
* Psychiatric comorbidities
* Neurologic comorbidities like Alzheimer's, Parkinson's, stroke with neurological deficit
* Unable to speak
* Bed-ridden status
* Post- Liver transplantation.

Primary outcomes:
measure: Handgrip Strength
timeFrame: 6 months
measure: Short Physical Performance Battery (SPPB)
timeFrame: 6 months
measure: Dual-energy X-ray absorptiometry (DEXA)
timeFrame: 6 months
measure: Mini-Mental Status Examination (MMSE)
timeFrame: 6 months
measure: Psychometric Hepatic Encephalopathy Score (PHES)
timeFrame: 6 months
measure: Animal Naming Test (ANT)
timeFrame: 6 months
measure: Blood cytokine levels [IL-6]
timeFrame: 6 months
measure: Blood ammonia levels [NH3]
timeFrame: 6 months
measure: Electroencephalogram (EEG)
timeFrame: 6 months
measure: Fecal Microbiota
timeFrame: 6 months
Secondary outcomes:
Other outcomes:
Locations:
city: Taoyuan
country: Taiwan
facility: Chang Gung Memorial Hospital
Study officials:
affiliation: Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan
name: CHIEN-HAO HUANG
role: PRINCIPAL_INVESTIGATOR
References: