Effect of BCAA Supplementation on Muscle Mass, Muscle Quality and Molecular Markers of Muscle Regeneration in CLD Patients

Chronic Liver Disease Clinical Trial

— BCAA-CLD  

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04246918
• Other study ID #: ILBS-BCAA-02
• Status: Completed
• Phase: N/A
• Start date: June 1, 2020
• Est. completion date: September 30, 2022

Study information

• Verified date: March 2022
• Source: Institute of Liver and Biliary Sciences, India
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: September 30, 2022
• Est. primary completion date: September 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Chronic Liver Disease
• Liver Diseases

Intervention

Dietary Supplement:
• Branched Chain Amino Acid
Branched chain amino acid is a group of three amino acids known for there role in muscle growth.
• Whey Protein concentrate powder
Whey protein will be given to the standard treatment arm including in the same amount of 1.5gm/kg/IBW.

Locations

Country	Name	City	State
India	Institute of Liver and Biliary Sciences	New Delhi	Delhi

Sponsors (1)

Lead Sponsor	Collaborator
Institute of Liver and Biliary Sciences, India

Country where clinical trial is conducted

India, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Improvement in the muscle mass	Muscle mass change as assessed by DEXA scan will be done.	3 months
Secondary	Changes in the muscle fibre type composition	Muscle fibre type will be assessed in muscle biopsy sample	3 months
Secondary	Changes in cross sectional area of muscle	Muscle fibre cross sectional area will be assessed in muscle biopsy sample	3 months
Secondary	Assessment of necrosis in muscle fibre	Muscle fibre necrosis will be assessed in muscle biopsy sample	3 Months
Secondary	Assessment of intramuscular fat deposition	Change in intramuscular fat deposition will be assessed in muscle biopsy sample.	3 months
Secondary	Assessment of myoD	Change in myoD will be assessed as marker of muscle regeneration in muscle biopsy sample	3 month
Secondary	Assessment of myogenin	Change in myogenin will be assessed as marker of muscle regeneration in muscle biopsy sample	3 months
Secondary	Assessment of PCNA	Change in PCNA as marker of satellite function will be assessed in muscle biopsy sample	3 months
Secondary	Assessment of proteosome C3, C5, C9	Change in these proteosome will be assessed in muscle biopsy sample	3 months
Secondary	Assessment of ubiquitin ligase E3	Change in Ubiquitin ligase E3 will be assessed in muscle biopsy sample.	3 months
Secondary	Assessment of myostatin level	Change in myostatin level will be assessed in blood sample using commercially available kit.	3 months
Secondary	Assessment of ammonia level	Change in ammonia level will be assessed in blood sample using commercially available kit	3 months
Secondary	Assessment of Insulin resistance	Insulin resistance will be calculated using homeostasis model for insulin resistance.	3 Month
Secondary	Assessment of IGF 1	IGF1 will be assessed using commercially available kit.	3 Month
Secondary	Assessment of Nutritional Status	Change Nutritional status will be assessed using bioelectrical impedance analysis	3 Month
Secondary	Assessment of Nitrogen balance	Change in nitrogen balance will be assessed using formula : Nitrogen Balance = Protein intake (gm) / 6.25 - (UUN + 4 gm)	3 Month
Secondary	Assessment of functional capacity	The Functional capacity of the patients would be assessed by Hand Grip Strength using the Handgrip Dynamometer .	3 Months
Secondary	Assessment of Clinical parameter- CTP	Clinical improvement will be assessed in terms of change in CTP score.	3 Months
Secondary	Assessment of Clinical parameter-MELD	Clinical improvement will be assessed in terms of change in MELD score.	3 Months
Secondary	Assessment of Health Related Quality of Life	The Health Related Quality of Life (HRQoL) of the patients would be assessed using the Chronic liver disease questionnaire(CLDQ)	3 Months