LiveSMART Trial to Prevent Falls in Patients With Cirrhosis
- Conditions
- Cirrhosis, LiverPortal Hypertension
- Interventions
- Behavioral: Enhanced Usual CareBehavioral: Investigator recommended exerciseBehavioral: TeleTai-Chi (virtual)
- Registration Number
- NCT05794555
- Lead Sponsor
- University of Michigan
- Brief Summary
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.
- Detailed Description
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. The caregivers that are enrolled are not in the clinical trial. Because all of the outcome measures in the supplemental study are other outcome measures (neither primary nor secondary to the trial) these are not included in this registration.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 430
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Clinical diagnosis of cirrhosis based on histology and/or imaging specified in the protocol.
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Evidence of portal hypertension - must meet at least one of the following criteria:
- Ascites (present or within past 2 years)
- Varices (seen by Esophagogastroduodenoscopy or by Ultrasound(US) or cross-sectional imaging)
- Fibroscan Liver stiffness measurement (LSM) >25 kilopascals (kPa) (if no other factors present)
- Magnetic resonance elastography (MRE) LSM > 5 kPa (if no other factors present)
- Acoustic radiation force impulse LSM > 17kpa (if no other factors present)
- Hepatic vein pressure gradient > 10 millimetres of mercury (mmHg)
- Portal hypertensive gastropathy seen on Esophagogastroduodenoscopy
- Platelet count < 80/ units per liter (uL)
- Recanalized umbilical vein (by US or cross-sectional imaging)
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Access to Wireless Fidelity (Wi-Fi) at home
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Owns or access to a smartphone, tablet or computer
-
English or Spanish speaking
-
Willing to participate in exercise program
- Overt hepatic encephalopathy (HE) within 6 months, requiring >28 days total of lactulose
- Took lactulose for non - HE reasons for >28 days total in last 6 months
- Took Rifaximin for > 28 days total in last 6 months
- Model for End Stage Liver Disease (MELD) > 25 (Exception: MELD > 25 with clinically stable End-Stage Renal Disease (ESRD) for whom the bilirubin is < 5 g/dL)
- Barcelona Clinic Liver Cancer (BCLC) > C Hepatocellular Carcinoma (HCC)
- Currently taking Sorafenib, Atezolizumab/Bevacizumab, Regorafinib, or Cabozatinib
- Greater than (>) 3 paracentesis/month in last 2 months
- Active Metastatic solid malignancy or acute leukemia within last 3 years
- Severe cognitive, vision, or hearing impairment (without use of corrective lenses or hearing assist devices) or psychiatric illness precluding study participation
- Currently participates in Tai-Chi or performs >150 min/week vigorous physical activity
- Currently receiving lower body physical and/or occupational therapy
- Living in an assisted living facility
- Hemoglobin A1C > 12 (within past 12 months)
- Requires a low galactose diet
- Deemed unsuitable by the study investigator
Inclusion Criteria for the Caregivers of the participants:
- Adult > 18 years of age
- Informal caregiver of a participant enrolled in LIVE-SMART
- English speaking
Exclusion Criteria for the Caregivers of the participants:
- Non-English speaking
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Enhanced Usual Care group Enhanced Usual Care Participants will be in stage 1 for approximately 12 weeks and then be re-randomized for stage 2. Treatment (Lactulose) group plus Enhanced Usual Care Enhanced Usual Care Participants will be in stage 1 for approximately 12 weeks and then be re-randomized for stage 2. Enhanced Usual Care group followed by investigator recommended exercise Enhanced Usual Care This is considered stage 2 for 12 weeks (for re-randomized participants). Enhanced Usual Care group followed by investigator recommended exercise Investigator recommended exercise This is considered stage 2 for 12 weeks (for re-randomized participants). Treatment (Lactulose) plus Enhanced Usual Care then TeleTai-Chi exercise classes Enhanced Usual Care This is considered stage 2 for 12 weeks (for re-randomized participants) Treatment (Lactulose) plus Enhanced Usual Care then TeleTai-Chi exercise classes TeleTai-Chi (virtual) This is considered stage 2 for 12 weeks (for re-randomized participants) Enhanced Usual Care group followed by Tele-Tai Chi exercise classes Enhanced Usual Care This is considered stage 2 for 12 weeks (for re-randomized participants) Treatment (Lactulose) plus Enhanced Usual Care then recommended exercise Enhanced Usual Care This is considered stage 2 for 12 weeks (for re-randomized participants) Enhanced Usual Care group followed by Tele-Tai Chi exercise classes TeleTai-Chi (virtual) This is considered stage 2 for 12 weeks (for re-randomized participants) Treatment (Lactulose) plus Enhanced Usual Care then recommended exercise Investigator recommended exercise This is considered stage 2 for 12 weeks (for re-randomized participants) Treatment (Lactulose) group plus Enhanced Usual Care Lactulose Participants will be in stage 1 for approximately 12 weeks and then be re-randomized for stage 2. Treatment (Lactulose) plus Enhanced Usual Care then TeleTai-Chi exercise classes Lactulose This is considered stage 2 for 12 weeks (for re-randomized participants) Treatment (Lactulose) plus Enhanced Usual Care then recommended exercise Lactulose This is considered stage 2 for 12 weeks (for re-randomized participants)
- Primary Outcome Measures
Name Time Method Number of patients experiencing a hierarchical composite of events over 24 weeks: injurious falls, non-injurious falls, incident Hepatic Encephalopathy, liver transplant, and death/transplant Baseline to 24 weeks (following stage 2) 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).
- Secondary Outcome Measures
Name Time Method Cognitive Function based on the Animal Naming Test (ANT) Baseline to 24 weeks (following stage 2) 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 stated (higher is better).
Days-alive and out-of-the-hospital Baseline to 24 weeks (following stage 2) Days-alive and out-of-the-hospital is a continuous value, 1 for each day alive, 0 for days in hospital. Participants will be queried and data will also be abstracted from the Electronic Medical Record (EMR).
Injurious Falls Baseline to 24 weeks (following stage 2) Falls include: Fracture, dislocation, cut, head injury, soft - tissue injury requiring hospitalization.
Non-Injurious Falls Baseline to 24 weeks (following stage 2) Non- Injurious Falls include: Inadvertently coming to rest on the floor or lower level
Incident Overt hepatic encephalopathy (HE) Baseline to 24 weeks (following stage 2) Incident Overt HE includes: Acute disorientation requiring hospitalization or the initiation of HE - directed therapy, confirmed by a gastroenterologist or study investigator.
Death/transplant Baseline to 24 weeks (following stage 2) Mortality with any cause or liver transplantation
Incident of Liver Transplant Baseline to 24 weeks (following stage 2) Replacement of a diseased liver with the healthy liver from another person.
Visual Analog Scale (VAS) Baseline to 24 weeks (following stage 2) This is 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.
Participant adherence 12 weeks and 24 weeks Adherence to lactulose, Tai-Chi, and nighttime protein supplementation will be monitored. Adherence is the proportion of expected-to-actual treatment days completed during the intervention.
Participant satisfaction with the trial and interventions based on the Patient Global Impression of Change (PGIC) 12 weeks and 24 weeks Satisfaction with the trial will be assessed using the 6-item Patient Global Impression of Change (PGIC). Participants select from Very much improved 1 - Very much worse 7. Lower scores indicate higher satisfaction.
The Patient Reported Outcome Measurement Information System (PROMIS)-29+2 v2.1 Baseline to 24 weeks (following stage 2) There are seven health domains including physical function, anxiety, depression, fatigue, sleep disturbances, ability to participate in social roles and activities, and pain interference. Each category consists of 4 questions. Questions are ranked on a 5-point Likert scale, with higher scores at times indicating better quality of life, and at other times indicating poorer quality of life. There is a pain rating scale ranging from 0 to 10, with higher scores indicating higher pain level.
Depression based on The Patient Reported Outcome Measurement Information System (PROMIS)-29+2 v2.1 Baseline to 24 weeks (following stage 2) There are 4 questions that participants complete regarding depression (never 1 - always 5). Scoring ranges (4-20) with higher scores indicating more depression.
Sleep quality based on the PROMIS-29+2 v2.1 Baseline to 24 weeks (following stage 2) There are 4 questions and are ranked on a 5-point Likert scale (not at all or very poor 1 - 5 very much). Scoring ranges (4-20) with lower scores indicating better sleep quality.
Physical frailty based on the Liver Frailty Index Baseline to 24 weeks (following stage 2) Physical frailty will be assessed with this index and is a composite of handgrip, timed chair-stands, and balance. The index ranges from -1.26 (robust) to 6.9 (frail), 50th percentile is 3.9. For individuals enrolled remotely, the study team will assess chair-stands.
Physical frailty based on the Activities of daily living (ADLs) Baseline to 24 weeks (following stage 2) 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
Intervention Fidelity 12 and 24 weeks Evaluation of intervention fidelity will be assessed at 50% and 100% of study completion as percent delivery of key intervention components including coordinator trainings, lactulose prescriptions ordered, enhanced usual care components delivered, Short Message Service (SMS) assessments sent, study visits completed, and exercise sessions completed.
Short Form (SF) - 8 12 weeks and 24 weeks 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 range 8-40, with a lower score meaning higher function.
Trial Locations
- Locations (3)
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