Trial Outcomes & Findings for PUSH Plus Protein Pilot for Hip Fracture Patients (NCT NCT03410823)

Participants were evaluated for eligibility in 3 phases out to 26 weeks post admission in 7 area hospitals (2019-2020). We screened 440 hip fracture patients at Phase 1 and 143 (32%) were eligible based on medical chart review. After Phase 2 and 3 screening, 20 (20%) people were enrolled and screened at Phase 2. Of those who consented, 3 were found to be ineligible at Phase 3, 2 refused, 1 was not able to have baseline testing within timeframe, and 14 participants completed baseline testing

Of those who consented, 3 were found to be ineligible at Phase 3, 2 refused, 1 was not able to have baseline testing within timeframe, and 14 participants completed baseline testing

PUSH Plus Protein Pilot for Hip Fracture Patients

The Six-Minute Walk Test (SMWT) will be used to obtain a continuous measure of total distance walked in six minutes. The SMWT is highly correlated with workloads, heart rate, oxygen saturation, and dyspnea responses when compared to bicycle ergometry and treadmill exercise tests in older persons. It has been performed by elderly, frail and severely compromised participants who cannot perform standard maximal treadmill or cycle ergometry exercise tests.

The Modified Mini-Mental State (3MS) is a widely used assessment of cognitive status. The 3MS test has a score range of 1-100 with higher scores indicating better cognitive function.

The SPPB evaluates lower extremity performance in older persons based on timed short distance walk, repeated chair stands, and a set of balance tests. Each of the tasks is assigned a score ranging from 0 to 4, with 4 indicating the highest level of performance and 0 an inability to complete the test. A higher score indicates better performance. The scores range from 0-12.

We will measure ADLs using a modified version of the Pepper Assessment Tool for Disability (PAT-D) with two modifications. First, two items (walking a quarter mile and walking across a small room) were added to address perceived gaps in the original PAT-D scale. This modification is consistent with the version used in the Lifestyle Interventions and Independence for Elders study. Second, two items (walking several blocks and lifting heavy objects) were deleted to avoid duplication with other items in the scale, resulting in a 19-item scale with higher scores indicating worse function. There are 3 subscales: Basic (score range 1-5), instrumental (score range 1-5), and functional (score range 1-5) (formerly mobility subscale).

We will use an interviewer-administered version of the SF-36 ( 36-Item Short Form Health Survey) , a health survey that assesses quality of life in eight subscales \[physical function, social function, role-physical, role-emotional, bodily pain, mental health, general health, and vitality\]. The SF-36 has been validated as a generic measure of quality of life in many different populations, including patient and non-patient samples. Each of the subscales has a score range of 0-100 and we only used 4 subscales (role-physical, vitality, social functioning, and role-emotional). Higher scores indicate higher quality of life through less disability across the 8 domains.

Nutritional status will be assessed using the Mini Nutritional Assessment-Short Form (MNA®-SF), a validated and widely used malnutrition screening tool. We are using a modified version of the MNA®, approved by the scale's developer (the Nestlé company), to facilitate use as an interviewer-administered tool in a research setting. Scores range from 0 to 14; participants scoring ≤7 will be considered malnourished; those scoring 8-11 will be considered to be at risk of malnutrition; and those scoring 12-14 will be considered to have normal nutritional status.

Bone density will be estimated using dual-energy x-ray absorptiometry (DXA) (GE LUNAR, Madison, WI). DXA calculates BMD (g.cm2) at the Total Hip and Femoral Neck regions and values are provided in the report produced by the DXA machine.

A single computed tomography (CT) scan at the mid-thigh region using a Siemens Somatom Sensation 64 Scanner (Fairfield, CT) was used to assess muscle area, high density lean tissue, and low density lean tissue area (IMAT),all on the fracture and non fracture sides. The CT was analyzed using MIPAV (NIH Image Analysis Visualization Progam, v.7.0).

A Biodex System 3 PRO dynamometer will measure strength per unit of time (power) for bilateral knee flexion-extension. Power is measured in Watts (W). Testing will utilize standardized positioning and joint motion excursions. Subjects performed three repetitions and the values across the three trials were averaged for the power value.

A Biodex System 3 PRO dynamometer will measure max power over the entire range of motion (strength) for bilateral knee flexion-extension. Strength is measured in Newton-meters (Nm). Testing will utilize standardized positioning and joint motion excursions. Subjects performed three repetitions and the values across the three trials were averaged for the strength value.

Bone formation (serum aminoterminal propeptide of type 1 procollagen; P1NP (ug/l)) will be assessed.

Bone resorption (serum cross-linked C-telopeptides of type I collagen; CTx-I (ng/mL)) will be assessed.

Insulin Growth Factor (IGF-1) will be measured by ELISA.

a) interleukin-6 (IL-6) and b) soluble TNF- α receptor 1 (sTNF- αR1). Both cytokines were measured in serum by ELISA (R\&D Systems Inc., Minneapolis, MN) and expressed at pg/ml levels.

A GAITrite instrumented walkway system will measure spatial and temporal gait parameters. Subjects will walk at their safest fast and natural speeds. Distance (spatial) variables will include step length (cm).Each participant completed two trials of each condition with a short rest period between trials for a total of four trials (i.e., 2 trials × 2 conditions). For each condition, values were averaged over the two trials. Walking aids were permitted only when the participant needed the aid to walk independently.

A GAITrite instrumented walkway system will measure spatial and temporal gait parameters. Subjects will walk at their safest fast and natural speeds. Time (temporal) variables include walking speed. Each participant completed two trials of each condition with a short rest period between trials for a total of four trials (i.e., 2 trials × 2 conditions). For each condition, values were averaged over the two trials. Walking aids were permitted only when the participant needed the aid to walk independently.

The Four Square Step Test (FSST) is used to assess dynamic stability and the ability of the subject to step over low objects forward, sideways, and backward. The FSST may be an effective and valid tool for measuring dynamic balance and the subject's fall risk.

The Trail Making Test is a neuropsychological test of visual attention and task switching. It consists of two parts in which the subject is instructed to connect a set of 25 dots as quickly as possible while still maintaining accuracy. The test can provide information about visual search speed, scanning, speed of processing, mental flexibility, as well as executive functioning. It is sensitive to detecting cognitive impairment associated with dementia.

Muscle and lean mass will be estimated using dual-energy x-ray absorptiometry (DXA) (GE LUNAR, Madison, WI). DXA calculates lean muscle mass (kg) from the total body scan and values are provided in the report produced by the DXA machine. The coefficient of variation of these measurements in our previous studies for lean mass was 1.3%.

A single computed tomography (CT) scan at the mid-thigh region using a Siemens Somatom Sensation 64 Scanner (Fairfield, CT) was used to assess muscle attenuation in Hounsfield units (HU) on the fracture and non fracture sides. The CT was analyzed using MIPAV (NIH Image Analysis Visualization Progam, v.7.0). HUs are used by radiologists to interpret CT images and differentiate between tissues and fluids. Muscle attenuation is a measure of muscle density that correlates with the amount of fat in the muscles. Lower HU values indicate higher levels of intramuscular fat. Therefore, decreased muscle attenuation has been linked to reduced strength and performance. A normal HU for low-density muscle is 0-34.

PTs will submit a visit form for each of the 32 visits that records date of visit; start and end time of the visit; reason for missed visit; what activities were performed; and whether activities were performed as prescribed. For the PUSH group, we will also obtain information about the intensity of each activity at initiation of the intervention and every four weeks during the intervention period. Logs completed by PTs will record the detail of each designated activity during intervention sessions as well as any precautions or modifications to activities. Reasons for protocol variations will be noted in the PT log books.

We will monitor adherence to the protein supplement by weighing the container(s) of protein powder every 4 weeks during the 16-week intervention period to derive an average daily consumption.