Clinical trial NCT06050668: Essential Amino Acid Supplementation for Femoral Fragility Fractures
Official title: MEND Repair & Recover Clinical Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Femoral Fracture
Fragility Fracture
Muscle Atrophy
Lead sponsor: University of Iowa
Sponsor class: OTHER
Collaborators: name: MEND
name: Slocum Research & Education Foundation
First posted: 2023-09-22
Enrollment: 60
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: This trial will evaluate the impact of 4 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.

Detailed description: This study consists of 7 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.

Preoperative

* 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 4 weeks after injury. Supplementation will begin within 72 hours of surgical fixation.

Day of Surgery (DOS):

* Muscle Biopsy: Bilaterial 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.

Postoperative Day 1 (POD 1)

* 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.
* Visual Analog Scale (VAS): This is a survey to report on subjective pain.
* 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
* Mini Nutrition Assessment (MNA): This is a survey designed for elderly patients to identify malnourishment or risk thereof. This survey is a computer adaptive test that is completed in REDCap® using a tablet or computer.
* Protein Screener: This is a survey designed for older adults to screen for low protein intake. This survey is a computer adaptive test that is completed in REDCap® using a tablet or computer.
* 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.
* Patients will be given an adverse event log to track any side effects or falls. We will encourage patients to call us but would like them to have a note sheet in case they forget.
* Patients randomized to the supplement group will be given a take home supplement log where they will track their AM and PM doses.
* All patients will be given logs to keep track of their daily pain, PT and number of meals eaten.

  3 Week Clinic Visit:
* Muscle biopsies
* Systemic inflammatory labs
* Body composition: InBody S10 Body Composition Analyzer
* Visual Analog Scale (VAS)
* Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function
* Barthel Activities of Daily Living Index
* Residence at a nursing home.
* Supplement Compliance: Patients will be asked to return completed log sheets and if they were randomized to the supplement group, being in their supplement containers to be weighed.

  6-Week Clinic Visit:
* Body composition: InBody S10 Body Composition Analyzer
* Visual Analog Scale (VAS)
* PROMIS Physical Function
* Barthel Activities of Daily Living Index
* Residence at a nursing home
* Supplement compliance

  12-week Clinic Visit:
* Body composition: InBody S10 Body Composition Analyzer
* Visual Analog Scale (VAS)
* PROMIS Physical Function
* Mini Nutrition Assessment (MNA)
* Protein Screener
* 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 Phone Call:
* PROMIS Physical Function
* Barthel Activities of Daily Living Index
* Residence at a nursing home

Eligibility criteria: 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
* Hemi or total arthroplasty (joint replacement)
* Patients with a historical diagnosis of chronic kidney disease (CKD)

Primary outcomes:
measure: Concentration and average count of satellite cells, myonuclei, M1, and M2 Macrophages for Type 1 and Type 2 fibers
timeFrame: Day of Surgery, 3 weeks
measure: Cross sectional concentration of Type 1 and Type 2 muscle fibers
timeFrame: Day of Surgery, 3 weeks
measure: Concentration of myostatin, interleukin-6, and tumor necrosis factor alpha
timeFrame: Day of Surgery, 3 weeks
measure: Concentration of c-terminal agrin fragments
timeFrame: Day of Surgery, 3 weeks
Secondary outcomes:
measure: Change in skeletal muscle
timeFrame: Postoperative day 1, 3 weeks, 6 weeks, 12 weeks
measure: Measurement of lower extremity functioning in older adults
timeFrame: 12 weeks
measure: Assessment of mobility, balance, walking ability, and fall risk in older adults
timeFrame: 12 weeks
measure: Measurement of self-reported physical capability
timeFrame: Post operative day 1, 3 weeks, 6 weeks, 12 weeks, 6 months
measure: Measurement of self-reported ability to complete activities of daily living (ADL)
timeFrame: Preoperative, 3 weeks, 6 weeks, 6 months
measure: Assessment of independent or communal living
timeFrame: Preoperative, 3 weeks, 6 weeks12 weeks, 6 months
Other outcomes:
Locations:
city: Iowa City
country: United States
facility: University of Iowa Health Care
state: Iowa
city: Eugene
country: United States
facility: Slocum Center for Orthopedics & Sports Medicine
state: Oregon
Study officials:
affiliation: University of Iowa
name: Michael C Willey, MD
role: PRINCIPAL_INVESTIGATOR
References: