Clinical trial NCT05794555: LiveSMART Trial to Prevent Falls in Patients With Cirrhosis
Official title: LiveSMART: A Sequential, Multiple Assignment Randomized Trial to Prevent Falls in Patients With Cirrhosis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Cirrhosis, Liver
Portal Hypertension
Keywords: Exercise program
Lactulose
Tai-Chi
Fall prevention
Dietary Protein
Lead sponsor: University of Michigan
Sponsor class: OTHER
Collaborators: name: Patient-Centered Outcomes Research Institute
First posted: 2023-04-03
Enrollment: 430
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Participants will be randomized in stage 1 to enhanced usual care or enhanced usual care plus lactulose. After 12 weeks participants will be re-randomized to TeleTai-Chi (at-home, via Zoom, supervised by a study team instructor) vs. continued enhanced usual care. The participants that took lactulose in Stage 1 will continue to take lactulose through Stage 2 until their participation is complete.

The observational sub-study will include enrollment of approximately 215 participants.
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* Clinical diagnosis of cirrhosis based on histology and/or imaging specified in the protocol.
* 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)
* Access to Wireless Fidelity (Wi-Fi) at home
* Owns or access to a smartphone, tablet or computer
* English or Spanish speaking
* Willing to participate in exercise program

Exclusion Criteria:

* 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

Primary outcomes:
measure: 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
timeFrame: Baseline to 24 weeks (following stage 2)
Secondary outcomes:
measure: Cognitive Function based on the Animal Naming Test (ANT)
timeFrame: Baseline to 24 weeks (following stage 2)
measure: Days-alive and out-of-the-hospital
timeFrame: Baseline to 24 weeks (following stage 2)
measure: Injurious Falls
timeFrame: Baseline to 24 weeks (following stage 2)
measure: Non-Injurious Falls
timeFrame: Baseline to 24 weeks (following stage 2)
measure: Incident Overt hepatic encephalopathy (HE)
timeFrame: Baseline to 24 weeks (following stage 2)
measure: Death/transplant
timeFrame: Baseline to 24 weeks (following stage 2)
measure: Incident of Liver Transplant
timeFrame: Baseline to 24 weeks (following stage 2)
measure: Visual Analog Scale (VAS)
timeFrame: Baseline to 24 weeks (following stage 2)
measure: The Patient Reported Outcome Measurement Information System (PROMIS)-29+2 v2.1
timeFrame: Baseline to 24 weeks (following stage 2)
measure: Depression based on The Patient Reported Outcome Measurement Information System (PROMIS)-29+2 v2.1
timeFrame: Baseline to 24 weeks (following stage 2)
measure: Sleep quality based on the PROMIS-29+2 v2.1
timeFrame: Baseline to 24 weeks (following stage 2)
measure: Physical frailty based on the Liver Frailty Index
timeFrame: Baseline to 24 weeks (following stage 2)
measure: Physical frailty based on the Activities of daily living (ADLs)
timeFrame: Baseline to 24 weeks (following stage 2)
measure: Intervention Fidelity
timeFrame: 12 and 24 weeks
measure: Participant adherence
timeFrame: 12 weeks and 24 weeks
measure: Participant satisfaction with the trial and interventions based on the Patient Global Impression of Change (PGIC)
timeFrame: 12 weeks and 24 weeks
measure: Short Form (SF) - 8
timeFrame: 12 weeks and 24 weeks
Other outcomes:
Locations:
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Dallas
country: United States
facility: Baylor Scott & White Research Institute (BSW)
state: Texas
Study officials:
affiliation: University of Michigan
name: Elliott Tapper, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Pennsylvania
name: Marina Serper, MD, MS
role: PRINCIPAL_INVESTIGATOR
References: