Effect of BCAA Supplementation on Muscle Mass, Muscle Quality and Molecular Markers of Muscle Regeneration in CLD Patients
Condition: Chronic Liver Disease
MeSH terms: Liver Diseases
Study type: Interventional

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.
    

Intervention name(s): Branched Chain Amino Acid; Whey Protein concentrate powder
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): Branched chain amino acid is a group of three amino acids known for there role in muscle growth.; Whey protein will be given to the standard treatment arm including in the same amount of 1.5gm/kg/IBW.
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Open Label
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Chronic Liver Disease; Sarcopenia; Myostatin; Health related quality of life; muscle histology