Muscle Atrophy, Physical Deconditioning
Conditions
Keywords
Falling risk, muscle conditioning, muscle size, isometric strength, Incidence in falls
Brief summary
This clinical trial will compare the effects of a high intensity Resistance Exercise via Negative Work (RENEW) vs. Traditional resistance exercise (TRAD) as part of a mult-component exercise and fall-reduction program on muscle conditioning; falling risks; as well as the fall incidence in older adults who have fallen. We anticipate that muscle conditioning will mediate the effect of RENEW on falling risks and fall incidence.
Detailed description
Muscle atrophy and weakness accompanying aging contributes greatly to an increased risk and incidence of falling. Over one-third of individuals 65 years of age or older experience a fall \[1,2\]. In a 2006 review \[3\] of 16 controlled (prospective and retrospective) studies \[4-8\] major factors affecting risk were identified with the most influential risk factors being muscle weakness, and deficits in balance and gait. The rate of muscle de-conditioning is accelerated by inactivity, muscle disuse and co-morbid conditions \[9-12\]. Older individuals with deficits in muscle size, strength and power can become so mobility-limited that simply walking to the mailbox is at the upper limit of their physical capacity \[9\] Hence, improving the muscle conditioning of an elderly individual with high fall risk may decrease the risk and incidence of falls \[13-18\]. Muscle conditioning often requires considerable effort, yet many elderly individuals lack the energetic reserves required for high-intensity exercise. Consequently, both elderly women and men are caught in a downward-spiral as their muscle de-conditioning accelerates the myriad risks of falling and the incidence of life-threatening falls. We have explored the safety and feasibility of a high-intensity Resistance Exercise via Negative, Eccentrically-induced Work (RENEW) in multiple groups of de-conditioned elderly males and females, many characterized as being at-risk for a fall due to their impaired muscle condition, balance, mobility and confidence. Compared to traditional resistance exercise (TRAD), RENEW is novel and advantageous in that RENEW: is a high-intensity exercise for muscle, yet requires little effort (resulting in high levels of adherence); induces unprecedented muscle conditioning (size, strength and power); and lowers falling risks (balance, mobility and confidence) \[19-23\]. This study is unique and timely because it is unknown if RENEW's amplified muscle conditioning translates to a decreased incidence of falls, particularly for those at the highest risk for an injurious fall, i.e. those who have fallen. Further, RENEW's long-term sustainability has not been explored. This clinical trial will compare the effects of RENEW vs. TRAD as part of a multi-component exercise and fall-reduction program (MCEFRP) on muscle conditioning (muscle size, strength, power); falling risks (balance, mobility and confidence); as well as the fall incidence. We anticipate that muscle conditioning will mediate the effect of RENEW on falling risks and fall incidence. As well, the sustained benefit of RENEW will be explored. Objective #1: Test whether RENEW's effect is different than TRAD's effect on muscle conditioning, i.e., muscle size, strength and power. • H1a: RENEW will result in greater increases (relative to TRAD) in whole muscle volume, isometric strength and concentric power of the leg extensor muscles, specifically the quadriceps. Objective #2: Test whether the effects of RENEW on falling risks is mediated by muscle conditioning. * H2a: RENEW will decrease falling risks (impaired balance, mobility and confidence) more than TRAD. * H2b: RENEW's effects on falling risks will be mediated by greater muscle conditioning. Objective #3: Determine if RENEW lowers fall incidence more than TRAD. • H3a: The RENEW intervention will result in a lower fall incidence (falls and near falls) than TRAD via the direct influence on muscle conditioning and via the indirect influence of decreasing falling risks.
Interventions
BEHAVIORALRENEW
RENEW will occur on a recumbent ergometer that appears like a normal stepper ergometer. While resisting the foot pedal movement the participant experiences eccentric muscle contractions about the knee and hip while performing negative work. The progression of the 3 x/week (every other day), 12 week RENEW program will be determined as a function of the rating of perceived exertion (RPE) using a target workload on the monitor. RENEW will be increased very slowly over the first 3 weeks and, subsequently, to maintain an 11-13 perceived exertion. During the formal RENEW training regimen the participants become fully acclimated to the device (week 3-4) the total RENEW load will increase weekly with no increase in their RPE.
Sponsors
National Institute on Aging (NIA)
Department of Health and Human Services
National Institutes of Health (NIH)
University of Utah
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
65 Years to 95 Years
Healthy volunteers
No
Inclusion criteria
* male or a female at least 65 years of age or older with 2 or more self-reported co-morbid conditions. * experienced at least 1 fall (defined for this study as unintentionally coming to rest on the ground, floor, or other lower level) in the previous 12 months * ambulatory, community dwelling with gait speed ranging from of 25m/min to 80m/min * medically cleared by their physician to participate in a 60 minute (with rests) MCERFP * capable of performing RENEW on the ergometer (see below) * recall of all 3 items (or 1-2 items with a normal clock drawing test) on the Mini-Cog instrument for dementia
Exclusion criteria
* progressive diagnosed neurologic disease (e.g., Parkinson's, multiple sclerosis, Guillain-Barre, Alzheimers) * any dystrophies or rheumatologic conditions that primarily affects muscle (muscular dystrophy, PMR) * having already participated in a MCEFRP * regular (3x/week) aerobic or resistance exercise performed over the past 12 months; aerobic defined as hiking, fast-walking, jogging, running swimming or cycling; resistance defined as weight training with bands, cable, free-weights or weight-machines * Any of the following list of absolute contraindications for MRI: * Cardiac Pacemakers (except in rare, controlled environments) * Cochlear (inner ear) implants * Swan-Ganz catheters with thermodilution tips * Ferromagnetic or unidentifiable aneurysm clips of the brain * Implanted neuro stimulators * Metal or unidentifiable foreign bodies in the eyes * Shrapnel near a vital organ * Extreme claustrophobia
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The Number of Days Survived Without a Fall Over the 1 Year Duration of the Study | 12 months |
Other
| Measure | Time frame | Description |
|---|---|---|
| Thigh Lean Tissue Cross Sectional Area (CSA) (cm^2) | 12 months | Magnetic resonance imaging (MRI) was used for determination of the cross-sectional area (CSA) (cm\^2) of lean muscle mass. Bilateral MRI scans of the thighs were obtained in a coronal plane and the midpoint of the thigh was determined and defined as halfway between the superior margin of the femoral head and the inferior margin of the femoral condyles. Axial imaging (5 mm thick slices at 1 cm intervals) of the legs was then performed over 1/2 the length of the femur, centered at the midpoint of the thigh. Five images from the middle 1/3 of each thigh were used to determine average CSA of lean tissue. |
| Leg Extension Power (W) | 12 months | Leg extension power in watts (W) of each leg individually was measured on a Nottingham power rig. After three warm-up trials at 50%, 75%, and 100% effort, six test trials and the average of the three highest trials per leg were recorded. |
| Activities Specific Balance Confidence (ABC) (%) | 12 months | Self-reported level of balance confidence was assessed with the Activities Specific Balance Confidence (ABC) Scale. This 16-item questionnaire asks participants to score their level of confidence in performing situation-specific activities such as reaching at eye level, reaching on tiptoes, picking up slipper from floor, and walking in crowded mall without losing . . . balance or becoming unsteady. Each item is scored from 0 to 100%, with 0% being no confidence and 100% being full confidence in the ability to perform the activity without losing balance. The total ABC Scale score is the average sum of the individual item scores. |
| Six Minute Walk (6 MW) Test | 12 months | The 6 min walk (6 MW) test, a measure of the distance (m) a subject walks in 6 min, was used to assess overall mobility. Self-selected gait-speed was measured over a 50-ft course. Individuals were instructed to walk at a comfortable pace starting at the word go. They were asked to walk out 25-ft and back. Timing took place from the command go until the starting line was crossed on the way back. Participants were allowed to use any walking aid they used on a daily basis. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| RENEW RENEW will occur on a recumbent ergometer that appears like a normal stepper ergometer. While resisting the foot pedal movement the participant experiences eccentric muscle contractions about the knee and hip while performing negative work. The progression of the 3 x/week (every other day), 12 week RENEW program will be determined as a function of the rating of perceived exertion (RPE) using a target workload on the monitor. RENEW will be increased very slowly over the first 3 weeks and, subsequently, to maintain an 11-13 perceived exertion. During the formal RENEW training regimen the participants become fully acclimated to the device (week 3-4) the total RENEW load will increase weekly with no increase in their RPE. | 68 |
| TRADITIONAL The TRAD group will perform their lower extremity resistance exercise for 15 minutes per session with isotonic weight machines and cuff weights as part of their MCERFP. The progression of the 3 x/week, 12 week TRAD program will be determined as a relative function of their 1 repetition maximum (RM) weight that can be lifted in a safe and successful manner. The 1RM will be measured before the 12 week training program and every 2 weeks thereafter. A target resistance workload (i.e., weight level) commensurate with 60-70% of the 1RM of the knee and hip extensors will be calculated bi-monthly and 3 sets of 15 repetitions of 3-4 different knee and hip exercises will be used over a 15 minute time period. | 66 |
| Total | 134 |
Baseline characteristics
| Characteristic | RENEW | TRADITIONAL | Total |
|---|---|---|---|
| Age, Continuous | 76.59 years STANDARD_DEVIATION 7.39 | 75.59 years STANDARD_DEVIATION 6.98 | 76.1 years STANDARD_DEVIATION 7.2 |
| Region of Enrollment United States | 68 participants | 66 participants | 134 participants |
| Sex: Female, Male Female | 45 Participants | 42 Participants | 87 Participants |
| Sex: Female, Male Male | 23 Participants | 24 Participants | 47 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 4 / 68 | 3 / 66 |
| serious Total, serious adverse events | 0 / 68 | 0 / 66 |
Outcome results
Primary
The Number of Days Survived Without a Fall Over the 1 Year Duration of the Study
Time frame: 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RENEW | The Number of Days Survived Without a Fall Over the 1 Year Duration of the Study | 239 Days survived without a fall. | Standard Error 18 |
| TRADITIONAL | The Number of Days Survived Without a Fall Over the 1 Year Duration of the Study | 249.67 Days survived without a fall. | Standard Error 16.38 |
Other Pre-specified
Activities Specific Balance Confidence (ABC) (%)
Self-reported level of balance confidence was assessed with the Activities Specific Balance Confidence (ABC) Scale. This 16-item questionnaire asks participants to score their level of confidence in performing situation-specific activities such as reaching at eye level, reaching on tiptoes, picking up slipper from floor, and walking in crowded mall without losing . . . balance or becoming unsteady. Each item is scored from 0 to 100%, with 0% being no confidence and 100% being full confidence in the ability to perform the activity without losing balance. The total ABC Scale score is the average sum of the individual item scores.
Time frame: 12 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| RENEW | Activities Specific Balance Confidence (ABC) (%) | 82.25 percent |
| TRADITIONAL | Activities Specific Balance Confidence (ABC) (%) | 80.93 percent |
Other Pre-specified
Leg Extension Power (W)
Leg extension power in watts (W) of each leg individually was measured on a Nottingham power rig. After three warm-up trials at 50%, 75%, and 100% effort, six test trials and the average of the three highest trials per leg were recorded.
Time frame: 12 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| RENEW | Leg Extension Power (W) | 104.73 watts |
| TRADITIONAL | Leg Extension Power (W) | 122.74 watts |
Other Pre-specified
Six Minute Walk (6 MW) Test
The 6 min walk (6 MW) test, a measure of the distance (m) a subject walks in 6 min, was used to assess overall mobility. Self-selected gait-speed was measured over a 50-ft course. Individuals were instructed to walk at a comfortable pace starting at the word go. They were asked to walk out 25-ft and back. Timing took place from the command go until the starting line was crossed on the way back. Participants were allowed to use any walking aid they used on a daily basis.
Time frame: 12 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| RENEW | Six Minute Walk (6 MW) Test | 439.18 meters |
| TRADITIONAL | Six Minute Walk (6 MW) Test | 438.15 meters |
Other Pre-specified
Thigh Lean Tissue Cross Sectional Area (CSA) (cm^2)
Magnetic resonance imaging (MRI) was used for determination of the cross-sectional area (CSA) (cm\^2) of lean muscle mass. Bilateral MRI scans of the thighs were obtained in a coronal plane and the midpoint of the thigh was determined and defined as halfway between the superior margin of the femoral head and the inferior margin of the femoral condyles. Axial imaging (5 mm thick slices at 1 cm intervals) of the legs was then performed over 1/2 the length of the femur, centered at the midpoint of the thigh. Five images from the middle 1/3 of each thigh were used to determine average CSA of lean tissue.
Time frame: 12 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| RENEW | Thigh Lean Tissue Cross Sectional Area (CSA) (cm^2) | 92.6 cm^2 |
| TRADITIONAL | Thigh Lean Tissue Cross Sectional Area (CSA) (cm^2) | 92.18 cm^2 |