Effects of Amino Acid Formulation on Healthy Men Undergoing Unilateral Knee Immobilization

This is a safety and tolerability study investigating the effect of an amino acid formulation in healthy volunteers during and after limb immobilization.

Study Overview

• Status: Completed
• Conditions: Muscle Atrophy
• Intervention / Treatment: Dietary supplement: Amino Acid; Device: Breg Brace single-leg immobilization; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8S4K1
      • McMaster Univeristy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Generally healthy, non-smoking
2. Willing and able to provide informed consent
3. Men age 20-45 years
4. BMI between 25 and 35 kg/m2

Exclusion Criteria:

1. Smoker;
2. Subject has any concurrent medical, orthopedic, or psychiatric condition that, in the opinion of the Investigator, would compromise his/her ability to comply with the study requirements;
3. History of cancer within the last 5 years, except basal cell carcinoma, non-squamous skin carcinoma, prostate cancer or carcinoma in situ with no significant progression over the past 2 years;
4. Significant orthopedic, cardiovascular, pulmonary, renal, liver, infectious disease, immune disorder (requiring ongoing medical care), or metabolic/endocrine disorder (e.g., diabetes, high cholesterol, elevated fasting blood sugar) or other disease that would preclude oral protein supplement ingestion and/or assessment of safety and study objectives;
5. Any cachexia-related condition (e.g., relating to cancer, tuberculosis or human immunodeficiency virus infection and acquired immune deficiency syndrome) or any genetic muscle diseases or disorders;
6. Current illnesses which could interfere with the study (e.g. prolonged severe diarrhea, regurgitation, difficulty swallowing);
7. Subject participated in a study of an investigational product less than 60 days or 5 half-lives of the investigational product, whichever is longer, before enrollment in this study;
8. Hypersensitivity to any of the components of the test product;
9. Excessive alcohol consumption (>21 units/week); (> 21 standard drinks/wk); e.g., 18oz glass of 5% beer - 1.5 standard drinks, a 750 mL bottle of 12% wine = 5 standard drinks.
10. Known sensitivity or allergy to amino acids or any ingredient in the test formulations;
11. Prior gastrointestinal bypass surgery (Lapband, etc.), irritable bowel disease or irritable bowel syndrome;
12. History of bleeding diathesis, platelet or coagulation disorders, or antiplatelet/anticoagulation therapy (up to 81mg of baby aspirin per day taken as a prophylactic is permitted);
13. Personal or family history of clotting disorder or deep vein thrombosis. Deep vein thrombosis is a serious, and potentially lethal, medical condition, therefore, it is imperative if you have personal or family history it is disclosed this to the research staff.
14. Concomitant use of corticosteroids, testosterone replacement therapy (ingestion, injection, or transdermal), any anabolic steroid, creatine, whey protein supplements, casein or branched-chain amino acids (BCAAs) within 45 days prior to Screening;
15. Contraindications to an MRI scan (e.g. subjects with non-removable ferromagnetic implants, pacemakers, aneurysm clips or other foreign bodies, or subjects with claustrophobic symptoms that would contraindicate an MRI scan).
16. Hemoglobin <11.5mg/dl at Screening;
17. Platelets <150,000/uL (150x109/L) at Screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Amino Acid; Subjects in this arm will receive amino acid supplementation (23.7g) 3 times daily for 28 days. Amino acids will be provided in powder form to be dissolved in 8oz of water. Participants will also undergo single-leg immobilization (Breg brace) for 7 days (days 8-15) during the 28 day study period.	Dietary supplement: Amino Acid; 23.7 g amino acid 3 times daily for 28 days; Device: Breg Brace single-leg immobilization; 7 days of single leg immobilization; randomized to leg; knee brace will be worn in a fixed flexion position at 140°.; Other Names: Breg brace
Placebo Comparator: Placebo; Subjects in this arm will receive placebo 3 times daily for 28 days. Placebo will consist of 23.7g of excipient-matched placebo in water. Participants will also undergo single-leg immobilization (Breg brace) for 7 days (days 8-15) during the 28 day study period.	Device: Breg Brace single-leg immobilization; 7 days of single leg immobilization; randomized to leg; knee brace will be worn in a fixed flexion position at 140°.; Other Names: Breg brace; Other: Placebo; Excipient-matched placebo 3 times daily for 28 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in muscle atrophy	To determine the impact of an amino acid formulation on muscle atrophy after 7 days of amino acid supplementation followed by 7 days of single leg immobilization and 14 days of recovery post-immobilization muscle atrophy will be assessed utilizing percutaneous muscle biopsy to quantify fibre size in the vastus lateralis.	day 0, day 8, day 15 and day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in muscle strength	Strength will be measured using a Biodex.	day 0, day 8, day 15 and day 28
Change in muscle size	Muscle size will be assessed via MRI.	day 0, day 8, day 15 and day 28

Collaborators and Investigators

• Sponsor: McMaster University
• Collaborators: Axcella Health, Inc

Publications and helpful links

General Publications

• Holloway TM, McGlory C, McKellar S, Morgan A, Hamill M, Afeyan R, Comb W, Confer S, Zhao P, Hinton M, Kubassova O, Chakravarthy MV, Phillips SM. A Novel Amino Acid Composition Ameliorates Short-Term Muscle Disuse Atrophy in Healthy Young Men. Front Nutr. 2019 Jul 10;6:105. doi: 10.3389/fnut.2019.00105. eCollection 2019.

Study record dates

Study Major Dates

• Study Start (Actual): August 30, 2017
• Primary Completion (Actual): December 19, 2017
• Study Completion (Actual): August 1, 2018

Study Registration Dates

• First Submitted: August 9, 2017
• First Submitted That Met QC Criteria: August 29, 2017
• First Posted (Actual): August 30, 2017

Study Record Updates

• Last Update Posted (Actual): June 19, 2019
• Last Update Submitted That Met QC Criteria: June 17, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Keywords: skeletal muscle; protein; immobilization
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Neuromuscular Manifestations; Pathological Conditions, Anatomical; Atrophy; Muscular Atrophy
• Other Study ID Numbers: 3365

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No