Frailty
Conditions
Keywords
frailty, sarcopenia, exercise, high intensity, older adults, microRNA
Brief summary
Frailty is a clinical condition of poor physiological reserve that increases risks for adverse health outcomes including falls, hospitalization and mortality. Exercise is beneficial for the prevention and even reversal of frailty, yet participation among older individuals is limited. Short session high intensity interval training (HIIT) is emerging as a promising exercise strategy that achieves performance gains with lower time commitment. The goal of this pilot proposal is to establish the feasibility of HIIT exercise training protocols in 65-85 year old individuals, as well as to demonstrate the ability to detect functional and physiologic benefits. The investigators anticipate the preliminary research findings will lay the foundation for future human clinical studies that will permit us to significantly improve the health of Veterans.
Detailed description
Enhancing functional capacity in older adults with short session high intensity interval training Frailty is a condition of poor physiological reserve that increases susceptibility to falls, hospitalization, disability and mortality. The incidence of frailty rapidly increases after the age 65, growing from 10% to as many as 50% of those 85 years or older; therefore over 9 million Veterans are either frail or at risk for frailty. Exercise has proven benefits for frailty, yet older adults rarely attain the recommended 150 minutes a week of moderate intensity exercise. High intensity interval training (HIIT) is emerging as an alternative as it delivers similar or better gains than moderate intensity exercise in less time. Recently, the investigators published that a 3-day-a-week, 10-minute HIIT regimen in aged mice not only reduces frailty, but leads to both strength and endurance benefits. In addition, the preliminary data demonstrate significant changes in microRNA (miRNA) profiles. Despite the potential of short session HIIT to improve functional capacity and lead to better adherence, the modality has not been tested in individuals 65-85 years of age, and in particular, frail individuals. The goals of this proposal are to: 1) investigate the feasibility of recruiting and administering short session HIIT to frail, pre-frail, and non-frail older Veterans and 2) to characterize the physical performance benefits and serum microRNA (miRNA) profiles in those participants. To accomplish these goals the investigators will administer a short session HIIT regimen totaling only 10-minutes, 3-days-a-week for 3 months, using recumbent exercise cycles, to 65-85 year old participants. The investigators will also utilize next generation RNA sequence technology to assess HIIT impacts upon microRNA profiles in serum samples. The investigators anticipate this project will demonstrate the feasibility of administering short session HIIT to older individuals, including vulnerable frail and pre-frail populations as well as demonstrate the ability to collect and analyze serum miRNA profiles. The advantages to this program are the ability to maintain or build muscle mass and improve aerobic conditioning, especially in older patients where frailty and sarcopenia are so prevalent. This pilot project will therefore lay the foundation for future clinical trials that further explore the utility of HIIT to prevent or delay the onset of frailty in larger cohorts, and ultimately lead to the enhancement of functional capacity and quality of life in aging Veteran populations.
Interventions
BEHAVIORALShort session HIIT
Individually tailored short session high intensity interval training session 3 times per week for 12 weeks on a recumbent exercise cycle.
Sponsors
The VA Western New York Healthcare System
University at Buffalo
Roswell Park Cancer Institute
VA Office of Research and Development
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
The goals of this proposal are to: 1) investigate the feasibility of recruiting and administering short session HIIT to frail, pre-frail, and non-frail older Veterans and 2) to characterize the physical performance benefits and serum microRNA (miRNA) profiles in those participants.
Eligibility
Sex/Gender
ALL
Age
60 Years to 85 Years
Healthy volunteers
Yes
Inclusion criteria
* Male or female * Any race * Frail, pre-frail, and non-frail * Medical clearance for exercise
Exclusion criteria
* Severe co-morbidity (e.g. - CHF (class III), COPD (GOLD stage IV), CKD (stage 3)) * VAMC SLUMS score 20 * Physical impairment that prevents use of a recumbent exercise bike
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 6-minute Walk at Baseline and Endpoint | baseline and at participant completion, an average of 3 months | 6-minute walk, total distance over 6 minutes in a 50 foot long hallway, participants asked to walk at a brisk pace. |
| Physical Activity Enjoyment at Baseline and Endpoint | baseline and at participant completion, an average of 3 months | Physical Activity Enjoyment Scale (PACES) that provides a valid instrument for assessing enjoyment in physical activity. There are 18 questions, each of which can receive a score from 1 to 7, where 7 is represents greater enjoyment. Scores presented as the mean across all questions giving an overall range of 1-7. |
| VO2max at Baseline and Endpoint | baseline and at participant completion, an average of 3 months | Performed as part of a symptom limited maximal endurance test on a cycle ergometer |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cognitive Survey at Baseline and Endpoint | baseline and at participant completion, an average of 3 months | VA-SLUMS: VA Saint Louis University Mental Status screen. Survey includes 11 questions allowing a range of scores from 1-30 points, where higher scores represent greater mental outcomes. |
| Activities of Daily Living & Instrumental Activities of Daily Living Survey at Baseline and Endpoint | baseline and at participant completion, an average of 3 months | The Activities of Daily living and instrumental activities of daily living are a survey comprised of 14 questions including ability to: dress, eat, ambulate, toilet, hygiene, shop, housework, accounting, food preparation, and use transportation/telephone. Each question gives up to 1 point with a total range of 0-14. Higher scores indicate less independence and greater reliance on support. |
| microRNA Profiling at Baseline and Endpoint | baseline and at participant completion, an average of 3 months | Next Generation Sequencing of microRNA species from serum. |
| Serum 25-hydroxy-vitamin D at Baseline | baseline | serum 25-hydroxy-vitamin D was measured from serum isolated from blood collected at baseline and measured using ELISA |
| C-reactive Protein Level at Baseline and Endpoint | baseline and at participant completion, an average of 3 months | C-reactive protein was measured from isolated serum samples at baseline and endpoint using ELISA |
| Short Physical Performance Battery at Baseline and Endpoint | baseline and at participant completion, an average of 3 months | Short Physical Performance Battery (SPPB) is an objective assessment tool for evaluating lower extremity functioning in older persons, including balance, side-by-side/semi-tandem/tandem stands, and gait speed. There are 3 subscales, each of which can receive from 0 to 4 points. Therefore the total range of the test spans summed scores from 0 to 12, where 12 is the best outcome. |
| FRAIL Scale Survey at Baseline and Endpoint | baseline and at participant completion, an average of 3 months | FRAIL scale: fatigability, resistance, ambulation, illnesses, loss of weight. If the answers to any of the questions is yes, then given score is 1 with a total survey range of 0 to 5. Higher scores represent greater frailty. |
| Serum Interleukin-6 Level at Baseline and Endpoint | baseline and at participant completion, an average of 3 months | Interleukin-6 collected from serum extracted from blood samples taken at baseline and endpoint and measured using ELISA |
| Serum Interleukin-10 Level at Baseline and Endpoint | baseline and at participant completion, an average of 3 months | Interleukin-10 collected from serum extracted from blood samples taken at baseline and endpoint and measured using ELISA |
| Number of Participants With Muscle Tissue Oxygenation Raw Data Collected | baseline and at participant completion, an average of 3 months | Seeking to collect raw data using functional near infra-red spectroscopy to analyze quadriceps during VO2max test. This work is the first steps in the development of techniques that analyze muscle blood flow and tissue oxygenation during exercise. |
| Quadriceps Strength at Baseline and Endpoint | baseline and at participant completion, an average of 3 months | Maximal quadriceps strength. This will be measured with the MicroFET2 dynamometer with a readout in kilograms (kg) of force. |
| Frailty at Baseline and Endpoint | baseline and at participant completion, an average of 3 months | Fried frailty phenotype assessment includes: gait speed, grip strength, endurance, activity level, weight loss. These assessments report summed scores of 0 to 5, where 0 is the best outcome. If gait speed or grip strength (m/sec or kg) falls within the lowest quintile (20%) for the age and gender adjusted range, then it is given a score of 1. If both questions on the endurance or activity measures are positive then then it is given a score of 1. If weight loss is greater than 5% over the past year, then it is given a score of 1. |
| Quality of Life Survey at Baseline and Endpoint | baseline and at participant completion, an average of 3 months | Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF). There are 14 subscales with scores of 1 to 5, where 5 is the better outcome. Therefore the total range of the test spans scores from 14 to 70, where 70 is the best outcome. The final score as a percentage with range being 0-100% and top being 100%. This percentage is calculated as: 100 \* ((participant's score - 14) / 56). |
Countries
United States
Participant flow
Recruitment details
Recruitment from 12/3/2018 - 12/31/2019. Recruitment occurred at the VA Western New York including through posted advertisements and word of mouth.
Pre-assignment details
11 individuals were excluded due to the COVID pandemic.
Participants by arm
| Arm | Count |
|---|---|
| HIIT Intervention Individually tailored short session high intensity interval training session 3 times per week for 12 weeks on a recumbent exercise cycle.
Short session HIIT: Individually tailored short session high intensity interval training session 3 times per week for 12 weeks on a recumbent exercise cycle. | 23 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | COVID PANDEMIC | 11 |
| Overall Study | Withdrawal by Subject | 8 |
Baseline characteristics
| Characteristic | HIIT Intervention |
|---|---|
| Age, Continuous | 71.9 years STANDARD_DEVIATION 6.8 |
| BMI | 30.6 kg/m^2 STANDARD_DEVIATION 0.6076 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 23 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 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 | 19 Participants |
| Region of Enrollment United States | 23 Participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 22 Participants |
| Smoking status Current Smoker | 2 Participants |
| Smoking status Former Smoker | 16 Participants |
| Smoking status Non-smoker | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 23 |
| other Total, other adverse events | 0 / 23 |
| serious Total, serious adverse events | 0 / 23 |
Outcome results
Primary
6-minute Walk at Baseline and Endpoint
6-minute walk, total distance over 6 minutes in a 50 foot long hallway, participants asked to walk at a brisk pace.
Time frame: baseline and at participant completion, an average of 3 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| HIIT Intervention | 6-minute Walk at Baseline and Endpoint | Baseline | 418.2 meters | Standard Deviation 72.2 |
| HIIT Intervention | 6-minute Walk at Baseline and Endpoint | Endpoint | 436.8 meters | Standard Deviation 55.6 |
p-value: 0.0238t-test, 2 sided
Primary
Physical Activity Enjoyment at Baseline and Endpoint
Physical Activity Enjoyment Scale (PACES) that provides a valid instrument for assessing enjoyment in physical activity. There are 18 questions, each of which can receive a score from 1 to 7, where 7 is represents greater enjoyment. Scores presented as the mean across all questions giving an overall range of 1-7.
Time frame: baseline and at participant completion, an average of 3 months
Population: One participant was not able to complete the assessment due to scheduling conflict.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| HIIT Intervention | Physical Activity Enjoyment at Baseline and Endpoint | Baseline | 6.1 Scores on a scale | Standard Deviation 0.8 |
| HIIT Intervention | Physical Activity Enjoyment at Baseline and Endpoint | Endpoint | 6.2 Scores on a scale | Standard Deviation 0.8 |
p-value: 0.3029t-test, 2 sided
Primary
VO2max at Baseline and Endpoint
Performed as part of a symptom limited maximal endurance test on a cycle ergometer
Time frame: baseline and at participant completion, an average of 3 months
Population: 8 participants were not able to complete the VO2max end point assessment due to COVID pandemic study cessation.~One participant was not able to complete the assessment due to scheduling conflict.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| HIIT Intervention | VO2max at Baseline and Endpoint | Baseline | 18.67 mL/min/kg | Standard Deviation 5.12 |
| HIIT Intervention | VO2max at Baseline and Endpoint | Endpoint | 19.93 mL/min/kg | Standard Deviation 5.59 |
p-value: 0.1713t-test, 2 sided
Secondary
Activities of Daily Living & Instrumental Activities of Daily Living Survey at Baseline and Endpoint
The Activities of Daily living and instrumental activities of daily living are a survey comprised of 14 questions including ability to: dress, eat, ambulate, toilet, hygiene, shop, housework, accounting, food preparation, and use transportation/telephone. Each question gives up to 1 point with a total range of 0-14. Higher scores indicate less independence and greater reliance on support.
Time frame: baseline and at participant completion, an average of 3 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| HIIT Intervention | Activities of Daily Living & Instrumental Activities of Daily Living Survey at Baseline and Endpoint | Baseline | 0.04 Score on a scale | Standard Deviation 0.21 |
| HIIT Intervention | Activities of Daily Living & Instrumental Activities of Daily Living Survey at Baseline and Endpoint | Endpoint | 0.0 Score on a scale | Standard Deviation 0 |
p-value: 0.366t-test, 2 sided
Secondary
Cognitive Survey at Baseline and Endpoint
VA-SLUMS: VA Saint Louis University Mental Status screen. Survey includes 11 questions allowing a range of scores from 1-30 points, where higher scores represent greater mental outcomes.
Time frame: baseline and at participant completion, an average of 3 months
Population: One participant was not able to complete the assessment due to scheduling conflict.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| HIIT Intervention | Cognitive Survey at Baseline and Endpoint | Baseline | 26.6 score on a scale | Standard Deviation 2.5 |
| HIIT Intervention | Cognitive Survey at Baseline and Endpoint | Endpoint | 27.3 score on a scale | Standard Deviation 2.3 |
p-value: 0.0219t-test, 2 sided
Secondary
C-reactive Protein Level at Baseline and Endpoint
C-reactive protein was measured from isolated serum samples at baseline and endpoint using ELISA
Time frame: baseline and at participant completion, an average of 3 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| HIIT Intervention | C-reactive Protein Level at Baseline and Endpoint | Baseline | 3.0 ug/uL | Standard Deviation 3.5 |
| HIIT Intervention | C-reactive Protein Level at Baseline and Endpoint | Endpoint | 3.7 ug/uL | Standard Deviation 3.7 |
p-value: 0.1563t-test, 2 sided
Secondary
FRAIL Scale Survey at Baseline and Endpoint
FRAIL scale: fatigability, resistance, ambulation, illnesses, loss of weight. If the answers to any of the questions is yes, then given score is 1 with a total survey range of 0 to 5. Higher scores represent greater frailty.
Time frame: baseline and at participant completion, an average of 3 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| HIIT Intervention | FRAIL Scale Survey at Baseline and Endpoint | Baseline | 0.2 Score on a scale | Standard Deviation 0.4 |
| HIIT Intervention | FRAIL Scale Survey at Baseline and Endpoint | Endpoint | 0.1 Score on a scale | Standard Deviation 0.3 |
p-value: 0.3282t-test, 2 sided
Secondary
Frailty at Baseline and Endpoint
Fried frailty phenotype assessment includes: gait speed, grip strength, endurance, activity level, weight loss. These assessments report summed scores of 0 to 5, where 0 is the best outcome. If gait speed or grip strength (m/sec or kg) falls within the lowest quintile (20%) for the age and gender adjusted range, then it is given a score of 1. If both questions on the endurance or activity measures are positive then then it is given a score of 1. If weight loss is greater than 5% over the past year, then it is given a score of 1.
Time frame: baseline and at participant completion, an average of 3 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| HIIT Intervention | Frailty at Baseline and Endpoint | Baseline | 0.87 score on a scale | Standard Deviation 0.8 |
| HIIT Intervention | Frailty at Baseline and Endpoint | Endpoint | 0.61 score on a scale | Standard Deviation 0.8 |
p-value: 0.1367t-test, 2 sided
Secondary
microRNA Profiling at Baseline and Endpoint
Next Generation Sequencing of microRNA species from serum.
Time frame: baseline and at participant completion, an average of 3 months
Population: RNA was isolated from participant serum samples and sequenced. However, none of the sequenced RNA were microRNA sequences, therefore analysis could not be performed. Consequently, there was no microRNA data that could be presented in a table.
Secondary
Number of Participants With Muscle Tissue Oxygenation Raw Data Collected
Seeking to collect raw data using functional near infra-red spectroscopy to analyze quadriceps during VO2max test. This work is the first steps in the development of techniques that analyze muscle blood flow and tissue oxygenation during exercise.
Time frame: baseline and at participant completion, an average of 3 months
Population: The goal of this project was to determine if raw functional near infrared spectroscopy data could be collected in participants. Data collection was verified. This work lays the foundation for future efforts in new experiments to determine methods to analyze the raw data to generate understandable data for interpretation - and lead to better understanding of the impacts of exercise on blood flow in muscle tissue.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HIIT Intervention | Number of Participants With Muscle Tissue Oxygenation Raw Data Collected | 10 Participants |
Secondary
Quadriceps Strength at Baseline and Endpoint
Maximal quadriceps strength. This will be measured with the MicroFET2 dynamometer with a readout in kilograms (kg) of force.
Time frame: baseline and at participant completion, an average of 3 months
Population: One participant was not able to complete the assessment due to scheduling conflict.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| HIIT Intervention | Quadriceps Strength at Baseline and Endpoint | Right Leg - Baseline | 27.7 kg | Standard Deviation 6.8 |
| HIIT Intervention | Quadriceps Strength at Baseline and Endpoint | Right leg - Endpoint | 31.1 kg | Standard Deviation 7.1 |
| HIIT Intervention | Quadriceps Strength at Baseline and Endpoint | Left leg - Baseline | 28.0 kg | Standard Deviation 7.9 |
| HIIT Intervention | Quadriceps Strength at Baseline and Endpoint | Left Leg - Endpoint | 29.9 kg | Standard Deviation 6.9 |
p-value: 0.011t-test, 2 sided
Secondary
Quality of Life Survey at Baseline and Endpoint
Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF). There are 14 subscales with scores of 1 to 5, where 5 is the better outcome. Therefore the total range of the test spans scores from 14 to 70, where 70 is the best outcome. The final score as a percentage with range being 0-100% and top being 100%. This percentage is calculated as: 100 \* ((participant's score - 14) / 56).
Time frame: baseline and at participant completion, an average of 3 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| HIIT Intervention | Quality of Life Survey at Baseline and Endpoint | Baseline | 80.0 % of Max Score | Standard Deviation 11.4 |
| HIIT Intervention | Quality of Life Survey at Baseline and Endpoint | Endpoint | 85.6 % of Max Score | Standard Deviation 9.6 |
p-value: 0.0111t-test, 2 sided
Secondary
Serum 25-hydroxy-vitamin D at Baseline
serum 25-hydroxy-vitamin D was measured from serum isolated from blood collected at baseline and measured using ELISA
Time frame: baseline
Population: No Statistical Analysis was performed as this was only a baseline measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HIIT Intervention | Serum 25-hydroxy-vitamin D at Baseline | 26.9 ng/ml | Standard Deviation 15.2 |
Secondary
Serum Interleukin-10 Level at Baseline and Endpoint
Interleukin-10 collected from serum extracted from blood samples taken at baseline and endpoint and measured using ELISA
Time frame: baseline and at participant completion, an average of 3 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| HIIT Intervention | Serum Interleukin-10 Level at Baseline and Endpoint | Baseline | 3.0 pg/mL | Standard Deviation 0.9 |
| HIIT Intervention | Serum Interleukin-10 Level at Baseline and Endpoint | Endpoint | 3.1 pg/mL | Standard Deviation 1.2 |
p-value: 0.5718t-test, 2 sided
Secondary
Serum Interleukin-6 Level at Baseline and Endpoint
Interleukin-6 collected from serum extracted from blood samples taken at baseline and endpoint and measured using ELISA
Time frame: baseline and at participant completion, an average of 3 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| HIIT Intervention | Serum Interleukin-6 Level at Baseline and Endpoint | Baseline | 3.8 pg/mL | Standard Deviation 1.9 |
| HIIT Intervention | Serum Interleukin-6 Level at Baseline and Endpoint | Endpoint | 4.2 pg/mL | Standard Deviation 2.4 |
p-value: 0.5244t-test, 2 sided
Secondary
Short Physical Performance Battery at Baseline and Endpoint
Short Physical Performance Battery (SPPB) is an objective assessment tool for evaluating lower extremity functioning in older persons, including balance, side-by-side/semi-tandem/tandem stands, and gait speed. There are 3 subscales, each of which can receive from 0 to 4 points. Therefore the total range of the test spans summed scores from 0 to 12, where 12 is the best outcome.
Time frame: baseline and at participant completion, an average of 3 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| HIIT Intervention | Short Physical Performance Battery at Baseline and Endpoint | Baseline | 10.11 score on a scale | Standard Deviation 2 |
| HIIT Intervention | Short Physical Performance Battery at Baseline and Endpoint | Endpoint | 10.46 score on a scale | Standard Deviation 2.1 |
p-value: 0.1261t-test, 2 sided