This multicenter trial is being conducted to determine if sequential lactulose and Tele (virtual) Tai-Chi reduces the rate of injurious fall, non-injurious falls, incident overt Hepatic Encephalopathy (HE), and death or liver transplant over 24 weeks. Participants that are enrolled will be randomized to stage one of this project for approximately 12 weeks. After completing stage one, participants will be re-randomized to stage 2 of the project that will last approximately 12 more weeks. The study hypothesizes that sequential lactulose/TeleTai-Chi will reduce falls, incident overt HE, death and physical frailty and will improve cognitive function, and Health Related Quality of Life (HRQOL) over 24 weeks compared to other treatment combinations. As detailed below, an observational component that enrolls caregivers of the trial participants is being conducted. Upon completion, Participants listed in the record here only include trial participants; and the observational component was moved to a new registration for clarity, NCT07140120.
The Clinicaltrials.gov registration record was updated as requested by Patient-Centered Outcomes Research Institute (PCORI) based on protocol amendment version 3.0 after approval by the Institutional Review Board. These changes included: the additional aim for a supplemental observational study to assess social determinants of health, financial burdens, etc., and includes recruitment of the caregivers for this supplemental study along with the trial participants, as well as updated outcomes for the trial. After further discussion with PCORI, these changes were removed from this record and used to create a separate record for the supplemental study focused on caregivers (NCT07140120). The caregivers that are enrolled are not in the clinical trial. All clinical trial information is provided in this record, but upon completion of enrollment and consideration of transparent results reporting, it was decided to move all the items related to the observational supplemental study to its own record. To improve clarity in the record, the two arms representing stage 1 of the project were incorporated into the remaining four representing stage 2, so the remaining arms now represent both stage 1 and stage 2.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
233
Patients will be provided and counseled on two methods which will enhance care. The first is a handout on nutrition recommendations and protein supplementation. This will include the recommendation of both high protein snacks during the daytime (e.g., protein bars) and a high-protein night-time snack (e.g., peanut butter and crackers). The second will be to counsel participants on falls prevention methods that can be enacted in day-to-day life. All participants will be provided with a standard hand-out of Centers for Disease Control and Prevention (CDC)-endorsed fall-risk reduction measures.
Patients will be prescribed lactulose and will also receive enhanced usual care. Lactulose will be taken on a specific schedule based on the average number of bowel movements on average per day. It will be started at 15 milliliter (mL) dose and will be instructed to slowly increase the lactulose dose over the course of the first week of Stage 1 participation. The prescribed maximum dose will be 30 mL (20g) twice daily. The dose will slowly increase toward the maximum or until participants reach 2-3 soft bowel movements daily. Participants that receive Lactulose during stage 1 will continue this in stage 2.
Participants randomized to enhanced usual care will be reminded of standard fall precautions outlined in the Fall Prevention Primer that were provided in Stage 1 and will receive exercise recommendations.
TeleTai-Chi will be taught remotely via live Zoom classes of up to 15 patients by a certified TeleTai-Chi instructor three times per week (for approximately 12 weeks). Classes will be conducted via a HIPAA-compliant Zoom server through the University of Michigan. Participants will be instructed to use Zoom by smartphone, tablet, or computer. High-Definition Multimedia Interface (HDMI) cables and other device specific equipment to connect devices to televisions will be provided.
University of Michigan
Ann Arbor, Michigan, United States
University of Pennsylvania
Philadelphia, Pennsylvania, United States
Baylor Scott & White Research Institute (BSW)
Dallas, Texas, United States
Number of Participants Experiencing a Hierarchical Composite of Events Over 24 Weeks: Injurious Falls, Non-injurious Falls, Incident Hepatic Encephalopathy, Liver Transplant, and Death/Transplant
Composite outcome is defined as any of the following: • Injurious Fall: Fracture, dislocation, cut, head injury, soft - tissue injury requiring medical intervention including: Hospitalization or overnight observation in the Emergency Room (ER); surgery, transfusion, stitches * Non - Injurious Fall: Inadvertently coming to rest on the floor or lower level * Include falls that result in minor injuries that are addressed with first aid (e.g., ice, bandage) * Incident Overt HE: Acute disorientation requiring hospitalization or the initiation of HE - directed therapy, confirmed by a gastroenterologist or study investigator * Death: Mortality with any cause * Liver transplant: Replacement of a diseased liver with the healthy liver from another person because of acute-on-chronic liver failure (using the EASL-CLIF-C definition consisting of an acute increase in the bilirubin and/or INR, acute kidney injury, overt HE, hypertension, and hypoxia).
Time frame: Baseline to 24 weeks
Injurious Falls
Results reflect the number of participants who experienced at least one injurious fall. Injurious falls include: Fracture, dislocation, cut, head injury, soft - tissue injury requiring hospitalization.
Time frame: Baseline to 24 weeks
Non-Injurious Falls
Results reflect the number of participants who experienced at least one non-injurious fall. Non- injurious falls include: Inadvertently coming to rest on the floor or lower level.
Time frame: Baseline to 24 weeks
Incident Overt Hepatic Encephalopathy (HE)
Incident Overt HE includes: Acute disorientation requiring hospitalization or the initiation of HE - directed therapy, confirmed by a gastroenterologist or study investigator.
Time frame: Baseline to 24 weeks
Death/Transplant for Acute-on-Chronic Liver Failure (ACLF)
Results reflect participants who died, or who received a liver transplant because of ACLF.
Time frame: Baseline to 24 weeks
Incident of Liver Transplant for Non-ACLF Reason
Results reflect the number of participants who received replacement of a diseased liver with the healthy liver from another person for any reason other than ACLF.
Time frame: Baseline to 24 weeks
Days-alive and Out-of-the-hospital
Days-alive and out-of-the-hospital is a continuous value, 1 for each day alive, 0 for days in hospital. Participants were queried and data was also abstracted from the Electronic Medical Record (EMR). Results reflect the average number of days participants were alive and out of the hospital.
Time frame: Approximately 26 Weeks
Change in Cognitive Function Based on the Animal Naming Test (ANT)
The animal naming test assesses cognitive function. It is a timed test that that consists of participants listing as many unique animals as possible in 60 seconds. This is a validated test used for the assessment of hepatic encephalopathy. The score is the number of unique animals named (higher is better). Results reflect change from baseline.
Time frame: Baseline to 24 weeks
Change in Visual Analog Scale (VAS)
This was a 1-item global rating of health scored 0-100. A score of 100 means the best health and 0 means the worst health imagined. Results reflect change from baseline.
Time frame: Baseline to 24 weeks
Change in The Patient Reported Outcome Measurement Information System (PROMIS)-29+2 v2.1 Profile (PROPr)
PROPr is the combined score of the two scales in the PROMIS 29+2, a quality-of-life scale and a pain-rating scale, and is used to calculate a preference score. The scores from both scales provide an overall summary of health-related quality of life based on multiple domains summarizing a metric ranging from 0 (as bad as dead) to 1 (perfect or ideal health). Results reflect change from baseline.
Time frame: Baseline to 24 weeks
Change in Depression Based on The Patient Reported Outcome Measurement Information System (PROMIS)-29+2 v2.1
There were 4 questions that participants completed regarding depression. The scores were converted to t scores, which were normalized from the raw scores. The t score ranged from 0-100 with 0 denoting worst depression and 100 indicating no depression. Results reflect the change from baseline.
Time frame: Baseline to 24 weeks
Change in Sleep Quality Based on the PROMIS-29+2 v2.1
There were 4 questions that participants completed regarding sleep quality. The scores were converted to t scores, which were normalized from the raw scores. The t score ranged from 0-100 with 0 denoting worst sleep quality and 100 indicating best sleep quality. Results reflect change from baseline.
Time frame: Baseline to 24 weeks
Physical Frailty Based on the Liver Frailty Index
Physical frailty was assessed with this index and was a composite of handgrip, timed chair-stands, and balance. The index ranged from -1.26 (robust) to 6.9 (frail), 50th percentile is 3.9. For individuals enrolled remotely, the study team assessed chair-stands.
Time frame: Baseline to 24 weeks
Change in Physical Frailty Based on the Activities of Daily Living (ADLs)
Activities of daily living (ADLs), is a validated self-reported measure (disability is defined as \>1 ADL deficit) recommended by the American Society for Transplantation and AASLD. The score ranged from 0 to 6 (6 indicating full independence, 4 moderate impairment, and 2 or less severe functional impairment). Results reflect change from baseline.
Time frame: Baseline to 24 weeks
Intervention Fidelity
Evaluation of intervention fidelity was assessed at 50% and 100% of study completion. Results reflect participants who maintained fidelity by completing at least one of the following key intervention components: coordinator trainings, lactulose prescriptions ordered, enhanced usual care components delivered, Short Message Service (SMS) assessments sent, study visits completed, or exercise sessions completed.
Time frame: 24 weeks
Participant Adherence
Adherence to lactulose, Tai-Chi, and nighttime protein supplementation was monitored. Results reflect the number of participants who discontinued their assigned intervention.
Time frame: 24 weeks
Participant Satisfaction With the Trial and Interventions Based on the Patient Global Impression of Change (PGIC)
Satisfaction with the trial was assessed using the 6-item Patient Global Impression of Change (PGIC). Participants selected from 1 (very much improved) to 7 (very much worse). Lower scores indicated higher satisfaction.
Time frame: 12 weeks and 24 weeks
Change in Short Form (SF) - 8
The SF-8 is an abbreviated 8-item version of an original 36-item health survey (SF-36). It is a generic multipurpose quality of life instrument. It contains psychometrically based physical and mental health summary measures. The eight domains include general health, physical functioning, role physical, bodily pain, vitality, social functioning, mental health and role emotional. The scores were converted to t scores, which were normalized from the raw scores. The t score ranged from 0-100 with 0 denoting worst quality of life and 100 indicating best quality of life. Results reflect change from baseline.
Time frame: 24 weeks
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