Effects of Aerobic and Resistance Exercises on Inpatients Liver Transplantation Recipients

Official title

Comparing the Effects of Aerobic and Resistance Exercises With Routine Physiotherapy in Inpatients Immediately After Liver Transplantation on Muscle Strength, Functional and Aerobic Capacity, and Blood Biomarkers

Overview

The prevalence of chronic liver disease and primary liver cancer is still increasing on a global scale, and so are their associated deaths. Compared to other diseases, death from liver disease often means premature death, because two-thirds of the lives lost are working years. Liver transplantation (LT) is an important and life-saving treatment option for the treatment of congenital metabolic disorders, acute liver failure, end-stage chronic liver disease (ESLD) and primary liver cancers. Modern liver transplantation is characterized by significant improvements in post-transplant patient survival, graft survival, and quality of life. Impaired physical fitness of patients with end-stage liver disease often persists after liver transplantation and compromises post-transplant recovery. Prior to liver transplantation, excess ammonia taken up by skeletal muscle is a major metabolic driver of muscle wasting in end-stage liver disease and mainly inhibits the mTOR signaling pathway that supports muscle protein synthesis. Because excess ammonia is no longer present after transplantation, recovery of muscle mass and function can be expected in patients. However, immunosuppression with calcineurin inhibitors that inhibit the mTOR signaling pathway may improve lethal length. It is also thought that post-transplant treatment regimens contribute to delayed recovery of decreased bone mineral density and increased fracture risk. Greater muscle mass, as measured by creatinine clearance at 1 year after transplantation, was associated with longer recipient and allograft survival. The results of previous studies indicate low cardiovascular fitness in patients after liver transplantation. Since after liver transplantation, cardiovascular diseases cause 19 to 42% of deaths not related to the liver, performing aerobic exercises to obtain and maintain cardiovascular fitness after liver transplantation can reduce the mortality rate. After transplanting, reduced significantly. Considering the important role of the immune system in transplant rejection, the safety of sports training is very important in terms of not over-activating the immune system and endangering the life of the transplanted tissue. In previous studies related to exercise and immune system activity and inflammatory cytokines after transplantation, it has been shown that moderate exercise including aerobic and resistance exercises can inhibit inflammatory cytokines and have beneficial effects on the immune system. High levels of tumor necrosis factor-alpha (TNF-α) in the period after transplant surgery are associated with an increased risk of transplant rejection. Aerobic exercise reduces levels of inflammatory cytokine TNF-α and markers of liver function in patients with chronic liver diseases. According to this evidence, it seems that doing sports exercises is effective in reducing the risk of transplant rejection and modulating the patient's immune system. Acute graft rejection occurs days to weeks after transplantation. The immune system can see the transplanted organ as foreign and attack it, destroy it and lead to transplant rejection. Considering the mentioned benefits of exercise therapy after liver transplantation, it is possible that the early start of exercise therapy in the hospitalization phase leads to a reduction in the risk of transplant rejection and improvement of allograft residues in patients after liver transplantation. Considering that the current evidence shows that there is no use of a specific rehabilitation protocol in the hospitalization phase of patients after liver transplantation, we intend to evaluate its effects with changes in the common physiotherapy program in these departments according to the specific conditions of these patients. In other words, despite the acceptable therapeutic effects, the use of a combined protocol of aerobic and resistance exercises in the hospitalization phase of these patients has not been reported so far.

Interventions

• Other Aerobic and resistance exercise
  From the first day of transplantation in the ICU until 10 days after transfer to the ward or discharge from the hospital, if needed, the patients of the group will undergo respiratory physiotherapy once a day. The process of this program includes patient assessment, clinical decision-making, and implementation of therapeutic interventions. The interventions of the therapeutic exercise group are divided into three phases: 1. From the time the patient enters the ICU until the time of extubation;
• Other Respiratory physiotherapy
  The participants of this group will receive respiratory physiotherapy daily after transplant until discharge.

Primary outcome measures

• Six-minute walk test [Time frame: Before transplantation (Day 0), after 10 sessions (An average three weeks), and three months after discharge (An average, 16 weeks)]

Secondary outcome measures (8)

• Muscle Strength [Time frame: Before transplantation (Day 0), after 10 sessions (An average three weeks), and three months after discharge (An average, 16 weeks)]
• Health-related quality of life [Time frame: Before transplantation (Day 0), after 10 sessions (An average three weeks), and three months after discharge (An average, 16 weeks)]
• Health-related quality of life (PLTQ) [Time frame: Before transplantation (Day 0), after 10 sessions (An average three weeks), and three months after discharge (An average, 16 weeks)]
• Cardiopulmonary exercise test [Time frame: Before transplantation (Day 0), after 10 sessions (An average three weeks), and three months after discharge (An average, 16 weeks)]
• The level of Urea [Time frame: Before transplantation (Day 0), after 10 sessions (An average three weeks), and three months after discharge (An average, 16 weeks)]
• The level of Creatinine [Time frame: Before transplantation (Day 0), after 10 sessions (An average three weeks), and three months after discharge (An average, 16 weeks)]
• The level of Interleukin-6 [Time frame: Before transplantation (Day 0), after 10 sessions (An average three weeks), and three months after discharge (An average, 16 weeks)]
• The level of Tumor Necrosis Factor-alpha [Time frame: Before transplantation (Day 0), after 10 sessions (An average three weeks), and three months after discharge (An average, 16 weeks)]

Eligibility criteria

Inclusion criteria

• Patients who undergo elective surgery after the approval of the liver transplant commission.
• Having an underlying liver disease with metabolic disorder (as determined by the Liver Transplantation Commission)
• Absence of transplantation of other organs
• No re-transplantation of the liver
• Age more than 18 years
• Ability to participate in initial evaluations
• Patient's ability to understand questionnaire questions

Exclusion criteria

• The patient's lack of satisfaction with continuing cooperation for any reason
• Re-transplantation up to 3 months after discharge
• Facing the patient with early allograft dysfunction or primary nonfunction
• Encountering the criteria of non-implementation of the intervention during 50% of the days of stay in the hospital or more
• Patients with Postoperative respiratory failure (Extubation > 48 hours)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

Iran · 1 center

• Liver Transplantation Research Center — Tehran

Identifiers

NCT: NCT06615934 · 65214

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗