Effect of BCAA Supplementation on Muscle Mass, Muscle Quality and Molecular Markers of Muscle Regeneration in CLD Patients (BCAA-CLD)
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|ClinicalTrials.gov Identifier: NCT04246918|
Recruitment Status : Recruiting
First Posted : January 29, 2020
Last Update Posted : February 10, 2021
|Condition or disease||Intervention/treatment||Phase|
|Chronic Liver Disease||Dietary Supplement: Branched Chain Amino Acid Dietary Supplement: Whey Protein concentrate powder||Not Applicable|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||60 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||Open Label|
|Masking:||None (Open Label)|
|Masking Description:||As it is a nutritional intervention study masking either the participant or the investigator is not possible.|
|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.|
|Actual Study Start Date :||June 1, 2020|
|Estimated Primary Completion Date :||October 31, 2021|
|Estimated Study Completion Date :||April 30, 2022|
Placebo Comparator: Standard Treatment Group
The patients would receive customized diet charts providing 30-35Kcal/ideal body wt/day and 1.5 gm protein/ideal body wt/day) describing the food items along with the quantity and approximate household measurements. Diet would be so planned for each patient keeping in mind the individual food habits and choices. This group would not receive any supplement other than the prescribed diet. Whey protein will be included in this group.
Dietary Supplement: Whey Protein concentrate powder
Whey protein will be given to the standard treatment arm including in the same amount of 1.5gm/kg/IBW.
Active Comparator: Intervention Arm
The patients would receive customized diet charts providing 30-35Kcal/ideal body wt/day and 1.5 gm protein/ideal body wt/day) describing the food items along with the quantity and approximate household measurements. Diet would be so planned for each patient keeping in mind the individual food habits and choices. In addition to the normal diet this group would receive 16gm of branched chain amino acid (BCAA) supplement (Commercial oral BCAA granules) daily in 4 divided doses, keeping the protein levels within the same range of 1.5 gm/Kg/day.
Dietary Supplement: Branched Chain Amino Acid
Branched chain amino acid is a group of three amino acids known for there role in muscle growth.
- Improvement in the muscle mass [ Time Frame: 3 months ]Muscle mass change as assessed by DEXA scan will be done.
- Changes in the muscle fibre type composition [ Time Frame: 3 months ]Muscle fibre type will be assessed in muscle biopsy sample
- Changes in cross sectional area of muscle [ Time Frame: 3 months ]Muscle fibre cross sectional area will be assessed in muscle biopsy sample
- Assessment of necrosis in muscle fibre [ Time Frame: 3 Months ]Muscle fibre necrosis will be assessed in muscle biopsy sample
- Assessment of intramuscular fat deposition [ Time Frame: 3 months ]Change in intramuscular fat deposition will be assessed in muscle biopsy sample.
- Assessment of myoD [ Time Frame: 3 month ]Change in myoD will be assessed as marker of muscle regeneration in muscle biopsy sample
- Assessment of myogenin [ Time Frame: 3 months ]Change in myogenin will be assessed as marker of muscle regeneration in muscle biopsy sample
- Assessment of PCNA [ Time Frame: 3 months ]Change in PCNA as marker of satellite function will be assessed in muscle biopsy sample
- Assessment of proteosome C3, C5, C9 [ Time Frame: 3 months ]Change in these proteosome will be assessed in muscle biopsy sample
- Assessment of ubiquitin ligase E3 [ Time Frame: 3 months ]Change in Ubiquitin ligase E3 will be assessed in muscle biopsy sample.
- Assessment of myostatin level [ Time Frame: 3 months ]Change in myostatin level will be assessed in blood sample using commercially available kit.
- Assessment of ammonia level [ Time Frame: 3 months ]Change in ammonia level will be assessed in blood sample using commercially available kit
- Assessment of Insulin resistance [ Time Frame: 3 Month ]Insulin resistance will be calculated using homeostasis model for insulin resistance.
- Assessment of IGF 1 [ Time Frame: 3 Month ]IGF1 will be assessed using commercially available kit.
- Assessment of Nutritional Status [ Time Frame: 3 Month ]Change Nutritional status will be assessed using bioelectrical impedance analysis
- Assessment of Nitrogen balance [ Time Frame: 3 Month ]Change in nitrogen balance will be assessed using formula : Nitrogen Balance = Protein intake (gm) / 6.25 - (UUN + 4 gm)
- Assessment of functional capacity [ Time Frame: 3 Months ]The Functional capacity of the patients would be assessed by Hand Grip Strength using the Handgrip Dynamometer .
- Assessment of Clinical parameter- CTP [ Time Frame: 3 Months ]Clinical improvement will be assessed in terms of change in CTP score.
- Assessment of Clinical parameter-MELD [ Time Frame: 3 Months ]Clinical improvement will be assessed in terms of change in MELD score.
- Assessment of Health Related Quality of Life [ Time Frame: 3 Months ]The Health Related Quality of Life (HRQoL) of the patients would be assessed using the Chronic liver disease questionnaire(CLDQ)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04246918
|Contact: Puja Bhatia, MScfirstname.lastname@example.org|
|Principal Investigator:||Puja Bhatia, MSc||Institute of Liver and Biliary Sciences|
|Study Director:||Jaya Benjamin, PhD||Institute of Liver and Biliary Sciences|