PUSH Plus Protein Pilot for Hip Fracture Patients

Community Ambulation Project (CAP) Ancillary Study - PUSH Plus Protein Pilot Study

Status

Terminated

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03410823

Enrollment

Registered

2018-01-25

Start date

2018-07-16

Completion date

2020-12-12

Last updated

2024-11-26

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Hip Fracture

Keywords

hip fracture, exercise, protein

Brief summary

Hip fracture is a common problem among older individuals. The goal of current standard of care after hip fracture is to achieve independent, household ambulation 2-3 months after surgery, yet decreased functional ability typically persists well beyond three months and many patients never resume independent ambulation outside the home. Previous research has established that one must be able to walk at least 300 meters (\ 330 yards) within 6 minutes to re-establish routine interactions in the community, such as going to the store or to church. In part, this is based on the average distance from handicapped parking spaces into most facilities. Activity and exercise are believed to be of benefit for reducing disability in older adults, yet the majority of older adults does not participate in regular exercise and is not active. This is especially true for older adults following hip fracture after they complete the usual rehabilitation program. This research study is being done to test a 16-week, multi-part exercise intervention for hip fracture patients that will be supervised by specially trained physical therapists (PTs). The exercise intervention uses a novel machine to provide strength and endurance training in the home. This has been shown in smaller studies to be safe and effective at increasing strength. The purpose of this small pilot study is to test whether adding a protein supplement to the exercise intervention leads to more improvements in a person's ability to walk in their own home and in the local community. With this knowledge, investigators hope to help a greater number of hip fracture patients enjoy a more complete recovery and improved overall health. In addition to providing important information on adherence, feasibility, and safety, this pilot study of hip fracture patients has the unique advantage of being able to compare data to two recently completed studies where participants received the PUSH intervention without protein supplementation.

Detailed description

A pilot study including 20 older adults who have experienced a hip fracture will be carried out with participants receiving a specific multi-component intervention with protein supplementation (PUSH Plus Protein). Study activities for participants meeting eligibility criteria will take place after post-acute rehabilitation ends, up to 26 weeks after admission to the hospital for hip fracture. Patients age 60 and older who have had surgical repair for hip fracture will be identified in study hospitals or by self-referral and evaluated for eligibility. Following consent to participate, eligible participants will undergo a comprehensive baseline assessment. Participants completing the entire baseline assessment will be eligible to receive the intervention. All participants will receive the PUSH Plus Protein intervention. The follow-up assessment will occur after the intervention is completed, approximately 16 weeks after baseline testing. The primary endpoint will be measured using the Six-Minute Walk Test (SMWT). Participants in this pilot will receive the same specific multi-component 16-week intervention, PUSH, as participants in the multi-site randomized controlled trial, Improving Community Ambulation after Hip Fracture (CAP) (NCT01783704). The purpose of this study is to test whether adding a protein supplement to the PUSH intervention (PUSH Plus Protein) leads to greater improvement in a person's ability to walk in their own home and in the local community compared to the PUSH intervention alone; therefore, data in this pilot study will be compared to data from participants in the CAP study across the three sites who received the PUSH intervention alone (n=105). The working hypothesis is that PUSH Plus Protein will lead to greater improvements in ability to walk in the community compared to PUSH. Investigators will also compare the effect of PUSH Plus Protein intervention to PUSH intervention alone on secondary outcomes in the CAP study believed to be precursors to community ambulation as shown in Aim 2 below. Investigators can also compare participants in the pilot study to participants who received PUSH alone in the ancillary study to CAP, Mechanistic Pathways to Community Ambulation (CAP-MP) (n=19) to examine whether PUSH Plus Protein has an impact on the mechanistic factors on the pathway to recovery of ambulatory ability after hip fracture (Aim 3). Aim 1. To test whether PUSH Plus Protein intervention improves community ambulation (as measured by distance walked in six minutes) compared to PUSH intervention alone (from CAP parent study) at the end of 16 weeks. Aim 2. To assess the effects of PUSH Plus Protein on precursors to community ambulation compared to the PUSH intervention alone (CAP study). To determine the effects of PUSH Plus Protein intervention, compared to PUSH, on several other outcomes in CAP including activities of daily living (ADLs), quality of life, lower-extremity physical performance, increase of ≥ 50 meters in distance walked in six minutes, cognitive status, and nutritional status. Aim 3. To determine the effects of PUSH Plus Protein intervention on the mechanistic factors compared to PUSH intervention alone (CAP-MP ancillary study). To determine if, at the end of the 16 week intervention, participants in the PUSH Plus Protein intervention, compared to PUSH alone, have: a) greater muscle volume and attenuation (i.e., reduced intra-muscular fat) of the thigh; b) greater lower extremity strength; c) better gait parameters; d) greater bone mineral density and bone strength; e) more bone formation and less bone resorption; and f) lower levels of circulating inflammatory cytokines. Aim 4. To determine safety and tolerability of delivering the PUSH Plus Protein intervention to hip fracture patients. This pilot study will be used to estimate the sample size requirements for a more definitive study.

Interventions

BEHAVIORALPUSH

Strength components of the muscle performance intervention are performed using a portable progressive resistive exercise device (Shuttle® MiniPress, Contemporary Design Company, P.O. Box 5089, Glacier, Washington 98244). Muscle performance focuses on bilateral hip extensors, hip abductors, knee extensors, and plantar flexors. Balance and strength are addressed with additional exercises performed while standing. The endurance intervention begins with 2-3 minutes of continuous upper and lower extremity active range of motion (AROM) with the participant sitting in order to increase the participants' heart rate (HR) or exertion closer to the target zone. The participant is then asked to walk on level surfaces and/or up and down steps to keep the HR within the training zone for 20 minutes.

DIETARY_SUPPLEMENTProtein

Participants will receive a whey-based protein supplement in the form of a powder containing 27.6g of protein. This dose induces maximum muscle protein synthesis post-exercise. Participants will mix the supplement in 8 oz of water (or other beverage) or soft food (e.g., yogurt, soup) and consume immediately following each exercise session with the study PT. On days when they do not have a physical therapy visit with the study PT, participants will be instructed to take the supplement at the meal time closest to the time of scheduled PT visits to maintain regular daily dosing schedule.

DIETARY_SUPPLEMENTNutrition

Participants receive 2000 IU vitamin D3, 600 mg calcium, and a multivitamin daily for the duration of the study. Nutritional counseling is also provided. Participants are screened at baseline to assess nutritional risk using the Mini Nutritional Assessment-Short Form and contacted by a registered dietician (RD) within 7 days of baseline testing Those who score ≤7 (malnourished) and participants with baseline serum albumin 2.5-3.5 g/dl receive a visit from an RD with follow-up a week later. Participants who score 8-11 (at risk of malnutrition) and have serum albumin level \>3.5 g/dl receive a phone call from the RD and may receive an in-person visit if warranted. Those screening in the normal range (12-14) and have serum albumin level \>3.5 g/dl receive a phone call from the RD. Weight is monitored every 4 weeks. Those who lose 2% or more body weight receive a call from the RD. Those who lose 5% or more body weight between baseline and follow-up may be referred to an RD.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

SUPPORTIVE_CARE

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

60 Years to No maximum

Healthy volunteers

Yes

Inclusion criteria

* Closed fracture of proximal femur * Age 60 or older at time of baseline testing * Minimal trauma fracture * Non-pathologic fracture * Surgical fixation of fracture * Living in the community at time of fracture * Ambulating without human assistance 2 months prior to fracture * Unable to walk 300 m or more in 6 minutes without human assistance at time of baseline testing

Exclusion criteria

* Not English speaking * Does not live within reasonable distance of the clinical center * End stage renal disease on dialysis * Recent myocardial infarction * Uncompensated congestive heart failure * Lower extremity amputation * Symptoms of angina pectoris * Chest pain or shortness of breath (including from severe COPD) * Participant plans to move out of area or otherwise be unavailable during the 16-week intervention period * Participation in another clinical trial * Not community-residing (e.g., resident of a skilled nursing facility) at time of baseline testing * Not fully weight-bearing on fractured leg or non-fractured leg at time of baseline testing * Calculated creatinine clearance \< 15 ml/min * Serum albumin \< 2.5 g/dl * Hemoglobin \< 9 g/dl * Receiving physical therapy for the hip fracture in the hospital or inpatient rehabilitation facility at time of baseline testing * Severely diminished lower extremity sensation or ulceration * Uncontrolled hypertension * Chronic kidney disease * Severe liver disease (e.g., hepatitis, fatty liver disease, cirrhosis) * Poorly controlled and/or insulin-dependent diabetes * Known dairy allergy * Denied medical clearance by appropriate medical provider * Clinical site clinician thinks participant is not a good candidate for study (e.g., not likely to survive study period) * Cognitive impairment (3MS score \<73) * Development of chest pain or substantial shortness of breath or ambulating with severe pain during baseline SMWT * Participant walks less than 4 meters in 40 seconds (\<0.1 m/sec) during baseline SMWT * Baseline testing not done by 26 weeks post admission for hip fracture * Final sign-off from study clinician and/or principal investigator is incomplete * Incomplete baseline data * Unable to contact participant * Participant is unable to provide her/his own informed consent * Participant refuses the study

Design outcomes

Primary

Measure	Time frame	Description
Distance Walked in Six Minutes	16 weeks	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.

Secondary

Measure	Time frame	Description
Cognitive Function (3MS)	16 weeks	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.
Short Physical Performance Battery (SPPB)	16 weeks	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.
Activities of Daily Living (ADLs)	16 weeks	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).
Quality of Life (SF-36)	16 weeks	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	16 weeks	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.
Body Composition- Done Density	16 weeks	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.
Muscle Composition	16 weeks	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).
Power	16 weeks	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.
Strength	16 weeks	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 Turnover Markers - Bone Formation	16 weeks	Bone formation (serum aminoterminal propeptide of type 1 procollagen; P1NP (ug/l)) will be assessed.
Body Composition- Lean Body Mass	16 weeks	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%.
Muscle Composition-attenuation	16 weeks	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.
Bone Turnover Markers - Bone Resorption	16 weeks	Bone resorption (serum cross-linked C-telopeptides of type I collagen; CTx-I (ng/mL)) will be assessed.
Hormones	16 weeks	Insulin Growth Factor (IGF-1) will be measured by ELISA.
Inflammatory Cytokines	16 weeks	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.
GAITrite Distance	16 weeks	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.
GAITrite Velocity	16 weeks	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.
Four-Square Step Test	16 weeks	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.
Cognitive Function (Trail Making Test (Trails A & B))	16 weeks	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.

Other

Measure	Time frame	Description
Adherence With PUSH Intervention	16 weeks	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.
Adherence With Protein Supplement	16 weeks	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.

Countries

United States

Participant flow

Recruitment details

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

Pre-assignment details

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

Participants by arm

Arm	Count
PUSH Plus Protein and Nutrition Participants received a whey-based protein powder containing 27.6g of protein per scoop taken daily for 16 weeks. Participants will mix the supplement in 8 oz of water (or other beverage) or soft food (e.g., yogurt, soup) and consume immediately following each exercise session with the study PT and at same time on other days of the week. Participants also received the PUSH intervention delivered in the home by a study PT \[2 times/wk for 32 visits (approx. 60 minutes per visit)\] over 16 weeks. Strength components of the muscle performance intervention were performed using a portable progressive resistive exercise device (Shuttle® MiniPress, Contemporary Design Company, P.O. Box 5089, Glacier, Washington 98244). Muscle performance focused on bilateral hip extensors, hip abductors, knee extensors, and plantar flexors. Balance and strength were addressed with additional exercises performed while standing. The endurance intervention began with 2-3 minutes of continuous upper and lower extremity active range of motion (AROM) with the participant sitting in order to increase the participants' heart rate (HR) or exertion closer to the target zone. The participant was then asked to walk on level surfaces and/or up and down steps to keep the HR within the training zone for 20 minutes. Participants also received the nutritional counseling and daily supplements (600 mg calcium, 2000 IU vitamin D, and multivitamin) for the duration of the 16-week study.	14
Total	14

Arm

Count

PUSH Plus Protein and Nutrition

Participants received a whey-based protein powder containing 27.6g of protein per scoop taken daily for 16 weeks. Participants will mix the supplement in 8 oz of water (or other beverage) or soft food (e.g., yogurt, soup) and consume immediately following each exercise session with the study PT and at same time on other days of the week. Participants also received the PUSH intervention delivered in the home by a study PT \[2 times/wk for 32 visits (approx. 60 minutes per visit)\] over 16 weeks. Strength components of the muscle performance intervention were performed using a portable progressive resistive exercise device (Shuttle® MiniPress, Contemporary Design Company, P.O. Box 5089, Glacier, Washington 98244). Muscle performance focused on bilateral hip extensors, hip abductors, knee extensors, and plantar flexors. Balance and strength were addressed with additional exercises performed while standing. The endurance intervention began with 2-3 minutes of continuous upper and lower extremity active range of motion (AROM) with the participant sitting in order to increase the participants' heart rate (HR) or exertion closer to the target zone. The participant was then asked to walk on level surfaces and/or up and down steps to keep the HR within the training zone for 20 minutes. Participants also received the nutritional counseling and daily supplements (600 mg calcium, 2000 IU vitamin D, and multivitamin) for the duration of the 16-week study.

Total

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Death	1
Overall Study	Withdrawal by Subject	2
Overall Study	Withdraw due to COVID-19 shutdown	2

Baseline characteristics

Characteristic	PUSH Plus Protein and Nutrition
3MS	89.93 units on a scale STANDARD_DEVIATION 9.08
6-minute walk test distance	180.12 meters STANDARD_DEVIATION 48.1
Age, Continuous	82.07 years STANDARD_DEVIATION 7.34
BMI	26.2 kg/m2 STANDARD_DEVIATION 6.09
Comorbidities	5.07 number of comorbidities STANDARD_DEVIATION 3.54
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	14 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants
Fracture type Femoral neck	4 Participants
Fracture type Pertrochanteric	10 Participants
MNA-SF	9.07 score on a scale STANDARD_DEVIATION 2.3
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	0 Participants
Race (NIH/OMB) Black or African American	0 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) White	14 Participants
Region of Enrollment United States	14 participants
Sex: Female, Male Female	10 Participants
Sex: Female, Male Male	4 Participants
SPPB	5.0 units on a scale STANDARD_DEVIATION 2.51

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	1 / 12
other Total, other adverse events	0 / 12
serious Total, serious adverse events	2 / 12

Outcome results

Primary

Distance Walked in Six Minutes

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.

Time frame: 16 weeks