Essential Amino Acid Supplementation for Femoral Fragility Fractures

Muscle Atrophy Clinical Trial

Official title:

MEND Repair & Recover Clinical Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06050668
• Other study ID #: 202307209-1
• Status: Not yet recruiting
• Phase: N/A
• Start date: February 2024
• Est. completion date: December 2025

Study information

• Verified date: December 2023
• Source: University of Iowa
• Contact: Michael C Willey, MD
• Phone: 319-384-8452
• Email: michael-willey[@]uiowa.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 60
• Est. completion date: December 2025
• Est. primary completion date: July 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 65 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Femoral Fracture
• Femoral Fractures
• Fractures, Bone
• Fragility Fracture
• Muscle Atrophy
• Muscular Atrophy

Intervention

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, ß-hydroxy ß-methylbutyrate (HMB)

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Michael C Willey	MEND

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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-a) will be measured in pg/mL.	Day of Surgery, 3 weeks
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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