Essential Amino Acid Supplementation for Femoral Fragility Fractures

MEND Repair & Recover Clinical Trial

This trial will evaluate the impact of 6 weeks of postoperative essential amino acid (EAA)-based supplementation on muscle morphology after femoral fragility fracture. This trial will assess the ability of EAA-based to increase skeletal muscle metabolic activity, reduce inflammation, and induce muscle fiber hypertrophy, as well as preserve skeletal muscle mass and physical performance up to 6 months after injury. Participants will be randomized in a 1:1 ratio to 1) standard of care (no dietary intervention) or 2) EAA-based supplementation.

Study Overview

• Status: Not yet recruiting
• Conditions: Femoral Fracture; Muscle Atrophy; Fragility Fracture
• Intervention / Treatment: Dietary supplement: Essential Amino Acid Supplementation

Detailed Description

This study consists of 5 study visits that occur over 6 months after operative fixation of femoral fragility fracture. Consenting participants will be asked to complete the study assessments/procedures at the time points described below. Patients will be treated with operative fixation of their fracture per standard of care.

Day of Surgery (DOS) Visit:

• Mini-Mental State Examination (MMSE-2®): This is a screening tool for cognitive impairment and will be used to determine eligibility for the study.
• Subjects will be randomized to the intervention arm or control arm in a 1:1 ratio. Subjects randomized to the control arm will receive standard of care nutrition during hospital admission. Subjects randomized to intervention arm of this study will receive essential amino acid (EAA)-based oral nutrition supplementation in addition to standard of care nutrition. Subjects will take the supplement twice daily for 6 weeks after injury. Supplementation will begin within 72 hours of hospital admission.
• Muscle Biopsy: Biopsies will be obtained from the superficial vastus lateralis muscle on the injury extremity. Biopsies will be performed by board-certified orthopedic surgeons.
• Systemic Inflammatory Labs: A sample of about 15 mL of peripheral venous blood will be obtained by trained clinical staff.
• Body composition: Will be assessed using a bioelectrical impedance analysis (BIA) device (InBody S10 Body Composition Analyzer). This is non-invasive test that uses a low-level imperceptible electrical current to measure body composition and body water. In a supine position, electrodes are placed on the hands and ankles of the subjects and the result is recorded in the BIA device. This assessment will be performed by trained study team members.
• Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function: This is a survey that asks subjects to report on subjective measures of pain and physical function. This survey is a computer adaptive test that is completed in REDCap® using a tablet or computer. Subjects will self-administer this survey
• Barthel Activities of Daily Living Index is a commonly used measure of activities of daily living outcomes for older adults. It measures the ability to perform activities of daily living that are important for maintaining function including feeding, bathing, grooming, dressing, bowel control, bladder control, toilet use, transfers from bed to chair and back, mobility on level surfaces, and stairs. Each measure is assessed on a 10-point scale, all scores are combined to give a score out of 100 points. The higher the score the more independent the individual.

• Residence at a nursing home will be recorded at each follow up visit. Participants living in an assisted living home (apartment or condominium with nursing assistance on call), apartment, single family home, or family member's home are considered living in the community.

  3 Week Clinic Visit:

• Muscle biopsy
• Systemic inflammatory labs
• Body composition: InBody S10 Body Composition Analyzer
• Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function
• Barthel Activities of Daily Living Index

• Residence at a nursing home.

  6-Week Clinic Visit:

• Body composition: InBody S10 Body Composition Analyzer
• PROMIS Physical Function
• Barthel Activities of Daily Living Index

• Residence at a nursing home

  12-week Clinic Visit:

• Body composition: InBody S10 Body Composition Analyzer
• PROMIS Physical Function
• Barthel Activities of Daily Living Index
• Residence at a nursing home

• Physical Performance Measures: Objective measures of physical performance (mobility, strength, power, & balance) will be assessed with the Short Physical Performance Battery (SPPB)14 and the Timed Up & Go (TUG)15 test. During the SPPB, subjects will complete the following physical assessments - ability to stand for 10 seconds with feet in 3 different positions (together side-by-die, semi-tandem, & tandem), two timed trials of a 4-meter walk, and time to rise from a chair 5 times. During the TUG, subjects will complete the following physical assessment - time to rise from a chair, walk 3 meters, return, & sit down. This assessment will be performed by trained study team members.

  6-month Clinic Visit:

• Body composition: InBody S10 Body Composition Analyzer
• PROMIS Physical Function
• Barthel Activities of Daily Living Index
• Residence at a nursing home
• Physical Performance Measures: Short Physical Performance Battery (SPPB)14 and the Timed Up & Go (TUG)15 test

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Michael C Willey, MD; Phone Number: 319-384-8452; Email: michael-willey@uiowa.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Hospital inpatient
• Age ≥ 65 years old on admission
• Low-energy mechanism of injury
• Diagnosis of femur fracture (OTA 31, 32, or 33 fracture)
• Indicated for surgical fixation
• Able to provide informed consent

Exclusion Criteria:

• Part of a vulnerable population (ex: Incarcerated, Non-English speaking)
• Cognitive impairment (MMSE score ≤ 17)
• Electrical medical implant (ex: Pacemaker/Defibrillator, Left Ventricular Assist Device, Cochlear implant, Insulin pump, Pain medication pumps, Spinal cord stimulator)
• Non-ambulatory prior to injury
• Inability to consume an oral diet or allergy to supplement ingredients (ex: milk allergy)
• Concern for inability to complete follow-up

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Essential Amino Acid Supplementation; Subjects randomized to intervention arm of this study will receive essential amino acid (EAA)-based oral nutrition supplementation in addition to standard of care postoperative nutrition. Subjects will take 1 scoop (26.7g) of supplement twice daily for 6 weeks after injury. Supplementation will begin within 72 hours of hospital admission. The EAA-based supplement used in this clinical trial is MEND™ Repair and Recover®.	Dietary supplement: Essential Amino Acid Supplementation; Powdered supplement that can be mixed into beverage of choice. Ingredients: Zinc, Vitamin A, Vitamin C, Whey Protein, Leucine, Calcium, Vitamin D, Glutamine, Boron, Turmeric, Bioperine, Iron, β-hydroxy β-methylbutyrate (HMB); Other Names: MEND Repair & Recover
No Intervention: Standard of Care Postoperative Nutrition; Subjects randomized to the control arm of this study will receive no intervention. They will receive standard of care postoperative nutrition.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concentration and average count of satellite cells, myonuclei, M1, and M2 Macrophages for Type 1 and Type 2 fibers	Biopsy results will provide the counts and averages by Type I and Type II fibers for satellite cells, myonuclei, M1 and M2 macrophages.	Day of Surgery, 3 weeks
Cross sectional concentration of Type 1 and Type 2 muscle fibers	Biopsy results will provide the Type I and Type II muscle fiber cross sectional area in µm2.	Day of Surgery, 3 weeks
Concentration of myostatin, interleukin-6, and tumor necrosis factor alpha	Through serum analysis levels of myostatin, interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α) will be measured in pg/mL.	Day of Surgery, 3 weeks
Concentration of c-terminal agrin fragments	Through serum analysis levels of c-terminal agrin fragment will be measured in ng/mL.	Day of Surgery, 3 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in skeletal muscle	Change in the amount of skeletal muscle mass will be measured by the InBody S10 Body Composition Analyzer and recorded in kilograms.	Day of Surgery, 3 weeks, 6 weeks, 12 weeks, 6 months
Measurement of lower extremity functioning in older adults	Physical performance in relation to lower extremity function will be measured by the Short Physical Performance Battery (SPPB) 14. Individuals are scored on a scale ranging from 0 (worst performance) to 12 (best performance) based on their walking speed, ability to do chair stands, and standing balance.	12 weeks, 6 months
Assessment of mobility, balance, walking ability, and fall risk in older adults	Physical performance in relation to mobility, balance, walking ability and fall risk will be measured by the Timed Up & Go (TUG) 15 test. For this test, the research coordinator measures the time required for a participant to rise from an armchair (45 cm height), walk 3 m and return to the chair. Longer times can indicate higher possibility of falling.	12 weeks, 6 months
Measurement of self-reported physical capability	Patient-reported physical performance will be measured using the PROMIS-Physical Function survey. PROMIS measures are scored on the T-score metric. a high score means the individual self-reports more of a capability at a certain activity.	Day of Surgery, 3 weeks, 6 weeks, 12 weeks, 6 months
Measurement of self-reported ability to complete activities of daily living (ADL)	Patient-reported physical performance of activities of daily living will be measured using the Barthel Activities of Daily Living Index. It is a commonly used measure of activities of daily living outcomes for older adults. It measures the ability to perform activities of daily living that are important for maintaining function including feeding, bathing, grooming, dressing, bowel control, bladder control, toilet use, transfers from bed to chair and back, mobility on level surfaces, and stairs. Each measure is assessed on a 10-point scale, all scores are combined to give a score out of 100 points. The higher the score the more independent the individual.	12 weeks, 6 months
Assessment of independent or communal living	Residence at a nursing home or living independently will be recorded at each follow-up visit. Participants living in an assisted living home (apartment or condominium with nursing assistance on call), apartment, single family home, or family member's home are considered living in the community. Living without assistance in a single dwelling will be considered living independently.	12 weeks, 6 months

Collaborators and Investigators

• Sponsor: Michael C Willey
• Collaborators: MEND
• Investigators: Principal Investigator: Michael C Willey, MD, University of Iowa

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2024
• Primary Completion (Estimated): July 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: August 28, 2023
• First Submitted That Met QC Criteria: September 18, 2023
• First Posted (Actual): September 22, 2023

Study Record Updates

• Last Update Posted (Estimated): December 14, 2023
• Last Update Submitted That Met QC Criteria: December 7, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Wounds and Injuries; Leg Injuries; Neuromuscular Manifestations; Pathological Conditions, Anatomical; Atrophy; Femoral Fractures; Muscular Atrophy; Fractures, Bone
• Other Study ID Numbers: 202307209-1

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