Clinical trial NCT04246918: Effect of BCAA Supplementation on Muscle Mass, Muscle Quality and Molecular Markers of Muscle Regeneration in CLD Patients
Official title: Effect of Branched Chain Amino Acids Supplementation on Muscle Mass, Muscle Quality and Molecular Markers of Muscle Regeneration in Patients With Chronic Liver Disease - A Randomized Controlled Trial.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Chronic Liver Disease
Keywords: Chronic Liver Disease
Sarcopenia
Myostatin
Health related quality of life
muscle histology
Lead sponsor: Institute of Liver and Biliary Sciences, India
Sponsor class: OTHER
First posted: 2020-01-29
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Open Label
Primary purpose: TREATMENT

Brief summary: Loss of muscle mass (sarcopenia) is a major complication in a patient with cirrhosis, impacting the disease outcome, quality of life and survival. Cirrhotics lose muscle mass (MM) while waiting for liver transplant (LT) and even after LT, impacting the outcome of LT. Moreover, LT is elusive for majority of patients in India. The pathophysiology of muscle loss is complicated, multifactorial, interlinked and primarily nutrition driven, which gives clues for targeted therapeutic modalities other than feeding alone. Experimental studies have instilled faith in BCAA in successfully counteracting the pathogenesis of muscle loss. But there is lack of convincing data from clinical studies with direct evidence on muscle growth per se.

Detailed description: Reduction in muscle mass (sarcopenia) is well documented in patients with chronic liver disease (CLD)leading to increased morbidity, mortality and poor quality of life. An equilibrium is maintained between the synthesis and degradation of muscles to maintain the muscle mass. However, an imbalance between the synthesis and degradation leads to loss of muscle mass. Various factors like alteration in dietary intake, hyper-metabolism, changes in amino acid profile, decreased physical activity, endotoxemia, hyperammonemia, increased myostatin levels have been postulated in the pathogenesis of muscle loss in liver disease. Reduced dietary intake, altered amino acid profile, decreased physical activity down regulate the anabolic pathway while the others increase the catabolic pathway. Increased level of myostatin inhibits the mTOR signaling and increases catabolism. Various therapeutic strategies such as increased calorie and protein intake, branched chain amino acid (BCAA) supplementation, late evening snack (LES), increased physical activity are the well accepted therapies. Hormone therapy (testosterone/growth hormone) also has been tried to improve muscle mass and function, reduce muscle catabolism in patients with CLD, however these newer treatment modalities i.e. hormone replacement, immune-nutrition and anti-myostatin antibodies are not free from adverse side-effects. Branched chain amino acids, a group of three essential amino acids (leucine, isoleucine, valine) have been tried since years in the setting of chronic liver disease patients for the treatment of hepatic encephalopathy and improvement in nutritional status. However, the studies assessing the impact of nutrition and BCAA in CLD have not assessed the direct impact on the muscle per se. The nutritional status has been assessed using different subjective methods like mid arm muscle circumference, triceps skin fold, nitrogen balance. Nutritional management is the cornerstone of the overall management of patients with cirrhosis, wherein BCAA constitutes an important therapeutic modality in the realm of nutrition in liver disease.

In the present study all the eligible cirrhotic patients will be randomized to a control group (receiving the nutritional therapy as per the standard nutritional practices and guidelines) or the intervention group (receiving BCAA supplementation over and above the standard nutrition therapy as per the standard nutritional practices and guidelines). Branched chain amino acids (BCAA) have the potential to up-regulate the anabolic pathway of muscle synthesis leading to improvement in muscle mass. Muscle mass as assessed by DEXA, along with changes in muscle histology, markers of the pathways that regulate muscle growth, functional capacity, and quality of life will be assessed after 3 months of BCAA intervention.

Eligibility criteria: Inclusion Criteria:

* Patients with decompensated cirrhosis (CTP 7-9)
* Adult patients Age 18-60 years
* Patients with corrected BMI in the range \<22.9
* Those who give consent for muscle biopsy
* INR \<1.5 or 1.5-2.5 after correction with Vitamin K
* Platelets \> 80000
* All etiologies

Exclusion Criteria:

* Presence of overt hepatic encephalopathy
* Patients with co-morbidities e.g. acquired immunodeficiency syndrome, HCC, Other cancer, Diabetes Mellitus, chronic kidney disease, congestive heart disease , chronic respiratory disease
* Patients with alcohol intake in past 3 months
* Patients with TIPS
* Patients on steroids
* INR \>2.5
* Refusal to participate in the trial

Primary outcomes:
measure: Improvement in the muscle mass
timeFrame: 3 months
Secondary outcomes:
measure: Changes in the muscle fibre type composition
timeFrame: 3 months
measure: Changes in cross sectional area of muscle
timeFrame: 3 months
measure: Assessment of necrosis in muscle fibre
timeFrame: 3 Months
measure: Assessment of intramuscular fat deposition
timeFrame: 3 months
measure: Assessment of myoD
timeFrame: 3 month
measure: Assessment of myogenin
timeFrame: 3 months
measure: Assessment of PCNA
timeFrame: 3 months
measure: Assessment of proteosome C3, C5, C9
timeFrame: 3 months
measure: Assessment of ubiquitin ligase E3
timeFrame: 3 months
measure: Assessment of myostatin level
timeFrame: 3 months
measure: Assessment of ammonia level
timeFrame: 3 months
measure: Assessment of Insulin resistance
timeFrame: 3 Month
measure: Assessment of IGF 1
timeFrame: 3 Month
measure: Assessment of Nutritional Status
timeFrame: 3 Month
measure: Assessment of Nitrogen balance
timeFrame: 3 Month
measure: Assessment of functional capacity
timeFrame: 3 Months
measure: Assessment of Clinical parameter- CTP
timeFrame: 3 Months
measure: Assessment of Clinical parameter-MELD
timeFrame: 3 Months
measure: Assessment of Health Related Quality of Life
timeFrame: 3 Months
Other outcomes:
Locations:
city: New Delhi
country: India
facility: Institute of Liver and Biliary Sciences
state: Delhi
Study officials:
affiliation: Institute of Liver and Biliary Sciences
name: Puja Bhatia, MSc
role: PRINCIPAL_INVESTIGATOR
affiliation: Institute of Liver and Biliary Sciences
name: Jaya Benjamin, PhD
role: STUDY_DIRECTOR
References: