PUSH Plus Protein Pilot for Hip Fracture Patients

Not Applicable

Terminated

• Conditions: Hip Fracture
• Interventions: Behavioral: PUSH; Dietary Supplement: Protein; Dietary Supplement: Nutrition

• Registration Number: NCT03410823
• Lead Sponsor: University of Maryland, Baltimore

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.

Study Timeline

• Study First Submitted: 2017-12-07
• Study First Submitted QC: 2018-01-18
• Study First Posted: 2018-01-25
• Study Start: 2018-07-16
• Primary Completion: 2020-12-12
• Study Completion: 2020-12-12
• Results First Submitted: 2024-05-17
• Status Verified: 2024-11
• Results First Submitted QC: 2024-11-01
• Last Update Submitted: 2024-11-01
• Results First Posted: 2024-11-26
• Last Update Posted: 2024-11-26

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 20

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
PUSH Plus Protein and Nutrition	PUSH	Participants will be given a whey-based protein supplement containing 27.6g of protein daily for 16 weeks and receive the PUSH intervention. PUSH is a specific multi-component intervention based on improving specific precursors to community ambulation. The intervention addresses endurance with continuous upright exercise for 20 min.; function by improving fast walking, standing from a chair, and stair negotiation; muscle performance by exercising to enhance lower extremity strength; and balance by performing unilateral activities and activities with decreased base of support. Participants receive 32 visits of approximately 60 minutes in duration from a study PT. Participants will receive two visits a week, on non-consecutive days, for 16 weeks. Visits take place in the participant's place of residence. Participants also receive the nutritional intervention for the duration of the 16-week study.
PUSH Plus Protein and Nutrition	Protein	Participants will be given a whey-based protein supplement containing 27.6g of protein daily for 16 weeks and receive the PUSH intervention. PUSH is a specific multi-component intervention based on improving specific precursors to community ambulation. The intervention addresses endurance with continuous upright exercise for 20 min.; function by improving fast walking, standing from a chair, and stair negotiation; muscle performance by exercising to enhance lower extremity strength; and balance by performing unilateral activities and activities with decreased base of support. Participants receive 32 visits of approximately 60 minutes in duration from a study PT. Participants will receive two visits a week, on non-consecutive days, for 16 weeks. Visits take place in the participant's place of residence. Participants also receive the nutritional intervention for the duration of the 16-week study.
PUSH Plus Protein and Nutrition	Nutrition	Participants will be given a whey-based protein supplement containing 27.6g of protein daily for 16 weeks and receive the PUSH intervention. PUSH is a specific multi-component intervention based on improving specific precursors to community ambulation. The intervention addresses endurance with continuous upright exercise for 20 min.; function by improving fast walking, standing from a chair, and stair negotiation; muscle performance by exercising to enhance lower extremity strength; and balance by performing unilateral activities and activities with decreased base of support. Participants receive 32 visits of approximately 60 minutes in duration from a study PT. Participants will receive two visits a week, on non-consecutive days, for 16 weeks. Visits take place in the participant's place of residence. Participants also receive the nutritional intervention for the duration of the 16-week study.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.
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%.
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.
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.
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.

Trial Locations

Locations (2)

University of Maryland, Baltimore; 🇺🇸 Baltimore, Maryland, United States

University of Maryland - St. Joseph Medical Center; 🇺🇸 Towson, Maryland, United States