Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04246918
Recruitment Status : Recruiting
First Posted : January 29, 2020
Last Update Posted : February 10, 2021
Sponsor:
Information provided by (Responsible Party):
Institute of Liver and Biliary Sciences, India

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.

Condition or disease Intervention/treatment Phase
Chronic Liver Disease Dietary Supplement: Branched Chain Amino Acid Dietary Supplement: Whey Protein concentrate powder Not Applicable

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
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.
Primary Purpose: Treatment
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

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Liver Diseases

Arm Intervention/treatment
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.




Primary Outcome Measures :
  1. Improvement in the muscle mass [ Time Frame: 3 months ]
    Muscle mass change as assessed by DEXA scan will be done.


Secondary Outcome Measures :
  1. Changes in the muscle fibre type composition [ Time Frame: 3 months ]
    Muscle fibre type will be assessed in muscle biopsy sample

  2. Changes in cross sectional area of muscle [ Time Frame: 3 months ]
    Muscle fibre cross sectional area will be assessed in muscle biopsy sample

  3. Assessment of necrosis in muscle fibre [ Time Frame: 3 Months ]
    Muscle fibre necrosis will be assessed in muscle biopsy sample

  4. Assessment of intramuscular fat deposition [ Time Frame: 3 months ]
    Change in intramuscular fat deposition will be assessed in muscle biopsy sample.

  5. Assessment of myoD [ Time Frame: 3 month ]
    Change in myoD will be assessed as marker of muscle regeneration in muscle biopsy sample

  6. Assessment of myogenin [ Time Frame: 3 months ]
    Change in myogenin will be assessed as marker of muscle regeneration in muscle biopsy sample

  7. Assessment of PCNA [ Time Frame: 3 months ]
    Change in PCNA as marker of satellite function will be assessed in muscle biopsy sample

  8. Assessment of proteosome C3, C5, C9 [ Time Frame: 3 months ]
    Change in these proteosome will be assessed in muscle biopsy sample

  9. Assessment of ubiquitin ligase E3 [ Time Frame: 3 months ]
    Change in Ubiquitin ligase E3 will be assessed in muscle biopsy sample.

  10. Assessment of myostatin level [ Time Frame: 3 months ]
    Change in myostatin level will be assessed in blood sample using commercially available kit.

  11. Assessment of ammonia level [ Time Frame: 3 months ]
    Change in ammonia level will be assessed in blood sample using commercially available kit

  12. Assessment of Insulin resistance [ Time Frame: 3 Month ]
    Insulin resistance will be calculated using homeostasis model for insulin resistance.

  13. Assessment of IGF 1 [ Time Frame: 3 Month ]
    IGF1 will be assessed using commercially available kit.

  14. Assessment of Nutritional Status [ Time Frame: 3 Month ]
    Change Nutritional status will be assessed using bioelectrical impedance analysis

  15. 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)

  16. 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 .

  17. Assessment of Clinical parameter- CTP [ Time Frame: 3 Months ]
    Clinical improvement will be assessed in terms of change in CTP score.

  18. Assessment of Clinical parameter-MELD [ Time Frame: 3 Months ]
    Clinical improvement will be assessed in terms of change in MELD score.

  19. 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)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

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


Contacts
Layout table for location contacts
Contact: Puja Bhatia, MSc 8586912966 pujabhatia27@gmail.com

Locations
Layout table for location information
India
Institute of Liver and Biliary Sciences Recruiting
New Delhi, Delhi, India, 110070
Contact: Jaya Benjamin, Dr    9540951081    jayabenjaminilbs@gmail.com   
Contact: Puja Bhatia, Ms    8586912966    pujabhatia27@gmail.com   
Sponsors and Collaborators
Institute of Liver and Biliary Sciences, India
Investigators
Layout table for investigator information
Principal Investigator: Puja Bhatia, MSc Institute of Liver and Biliary Sciences
Study Director: Jaya Benjamin, PhD Institute of Liver and Biliary Sciences
Layout table for additonal information
Responsible Party: Institute of Liver and Biliary Sciences, India
ClinicalTrials.gov Identifier: NCT04246918    
Other Study ID Numbers: ILBS-BCAA-02
First Posted: January 29, 2020    Key Record Dates
Last Update Posted: February 10, 2021
Last Verified: February 2021

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Institute of Liver and Biliary Sciences, India:
Chronic Liver Disease
Sarcopenia
Myostatin
Health related quality of life
muscle histology
Additional relevant MeSH terms:
Layout table for MeSH terms
Liver Diseases
Digestive System Diseases