Study design
This will be a single-blinded, multicenter, randomized controlled trial that will recruit participants from three community-based primary care clinics over a 24-week follow-up period. Possible sarcopenia outcomes will be evaluated four times: before the intervention (baseline), during the intervention (6 weeks), immediately after the intervention (12 weeks), and 12 weeks after completing the intervention (24 weeks, which is the total study duration).
Provisional study schedule
- Start of study: August 2023.
- Recruitment period: August 2023 to October 2024.
- Follow-up period: 24 weeks.
- Total duration of the study: 15 months.
Participant recruitment and eligibility criteria
Recruitment notices have been posted on bulletin boards in the waiting areas of local primary care clinics, magazine holders, and bulletin boards in the examination rooms. Three collaborating researchers affiliated with local primary care clinics will recruit eligible participants, and the number of participants recruited by each clinic will vary. To ensure that the target number of participants is met, research coordinators from Kyung Hee University Hospital will oversee and manage the recruitment of participants in each clinic. The researchers will obtain informed consent from the participants. After confirming the eligibility of the participants, researchers will proceed with the screening step [5].
Community-based primary care clinic older outpatients (47 participants in the control group and 47 participants in the intervention group, aged 65–85 years) with possible sarcopenia will be included in this trial. Possible sarcopenia will be defined as follows [1]:
(1) SARC-F questionnaire or calf circumference
SARC-F questionnaire score is ≥4; or
For men: positive if calf circumference is <34 cm
For women: positive if calf circumference is <33 cm
(2) Hand grip strength
For men: positive if grip strength is <28 kg
For women: positive if grip strength is <18 kg
(3) 5-times chair stand test
5-times chair stand test time is ≥12 seconds for both sexes
If conditions (1) and [(2) or (3)] are met, participants will be considered as having possible sarcopenia.
The exclusion criteria are as follows: creatinine level >2.0 mg/dL; uncontrolled systolic and diastolic blood pressure (BP) (>150 mm Hg systolic BP or >90 mm Hg diastolic BP) or uncontrolled blood glucose level (HbA1c >7.5%); receipt of treatment that can affect muscle mass, such as steroid or chemotherapy; serious or life-threatening medical histories: myocardial infarction, angina, liver cirrhosis, or stroke; previous cancer history within five years or ongoing chemotherapy treatment; elevated liver enzymes exceeding three-times the upper threshold limit or medical history of hepatitis; allergy to protein supplement ingredients such as soybean; and inability to engage in physical activity due to musculoskeletal or chronic disease.
Randomization and blinding
Participants will be allocated into control and intervention groups to compare pre- and post-intervention outcomes using a randomization table. The allocation ratio for both groups will be 1:1. Owing to the nature of the comparative study on the effects of exercise and nutrition education, blinding of the participants is not feasible. A single-blind test will be conducted, in which only the evaluator will be blinded (Figure 1).
Detailed description of the combined exercise and nutrition intervention
Based on a previous study, the intervention group will receive a 12-week exercise program with nutritional support, whereas the control group will only receive educational materials without intervention for 12 weeks [32].
Exercise intervention
The body weight and BP of the participants will be measured before the start of each exercise session. Following the guidelines of the American College of Sports Medicine, participants with resting (pre-exercise) systolic BP of ≥200 mm Hg or diastolic BP of ≥110 mm Hg will be excluded [33]. Participants with BP measurements that meet the exclusion criteria at any visit during the study will be also excluded for safety reasons.
The exercise intervention will be conducted under the guidance of research personnel and will be performed face-to-face in a separate exercise room provided by each clinic, with each group consisting of up to four participants. The 12-week exercise intervention consists of three phases: an introductory phase (for 3 weeks: twice-weekly visits to the clinic and once-weekly home exercises), an expanded phase (for 3 weeks: twice-weekly visits to the clinic and once-weekly home exercises), and a maintenance phase (for 6 weeks: once-weekly visit to the clinic and twice-weekly home exercises). The intervention includes stretching, resistance exercises (during both clinic visits and at home), and aerobic exercises (at home only), and each session lasts a maximum of 40 minutes.
This step-by-step approach to resistance exercise focuses on different levels of resistance using TheraBands and chair-based exercises. The introductory phase starts with light resistance and gradually progresses to moderate resistance, followed by strong resistance in the subsequent phases. Emphasis on concentric contractions helps build muscle strength effectively. This structured progression will ensure a balanced and controlled approach for strength improvement over the course of the intervention. The expansion phase emphasizes on eccentric contractions, whereas the maintenance phase emphasizes on power and eccentric exercises (Figure 2). The exercise components are described below:
(1) Stretching
A five-to-ten–minute stretching routine targeting major muscle groups will be conducted before and after the exercise sessions. This will include preparatory and cooldown stretches for key muscle groups.
(2) Resistance exercise
We selected a few major paired (agonist–antagonist) muscle groups, including the knee and elbow flexor extensors, for resistance exercise training, ensuring a possible full range of motion on both sides [23]. The resistance exercise will consist of four upper body exercises (biceps curls, dips, front raises, and chest presses) and five lower-body exercises (leg lateral rotations, leg extensions, hip abductions, squats, and heel raises). Resistance exercises will utilize TheraBands (resistance bands) and body weight for chair-based exercises. The exercise intensity and intensity of the resistance bands will be customized according to the participants' strength levels. Exercise intensity will be induced to create overload using factors such as repetition count and Rating of Perceived Exertion. The number of sets and exercise durations will increase gradually over time.
(3) Aerobic exercise
The program will include home-based exercises, such as walking and stationary bicycles, to be performed at least five times a week, with each session lasting for >30 minutes.
The phases of the exercise intervention are described below:
(1) Introductory phase (3 weeks): upper- and lower-body exercises, 8–10 repetitions in three sets (using very light and light resistance bands).
(2) Expansion phase (3 weeks): upper- and lower-body exercises, 10–12 repetitions in three sets (using light and moderate resistance bands).
(3) Maintenance phase (6 weeks): upper- and lower-body exercises, 15 repetitions in three sets (using moderate and vigorous resistance bands).
Nutrition intervention
For the nutrition intervention, individual dietary counseling will be provided by a clinical nutritionist and will be tailored to the nutritional status and individual eating patterns of each study participant. The goal of this food intake strategy will be to allow the participants to achieve optimal nutrition and high protein intake. After evaluating the nutritional status of the participants using the Mini-Nutritional Assessment (MNA), the daily protein intake goal will be determined depending on the MNA scores: score of 24–30 (well-nourished), 1.2 g/kg/day; score of 17.0–23.5 (at risk), 1.5 g/kg/day; and score of <17 (malnourished), 1.5 g/kg/day.
Participants with MNA scores of 17.0–23.5, indicating risk of malnutrition, will receive a maximum of two packs of supplementary protein products daily; those with MNA scores of <17, indicating malnourishment, will receive a maximum of three packs daily.
According to the Nutritional Intervention Guidelines, supplementary protein products (Mediwell, Korea Medical Foods, Seoul, South Korea; 150 kcal per serving [150 mL], protein: 8 g, fat: 5 g, dietary fiber: 3 g, total carbohydrate: 20 g, sugar: 2 g), which is equivalent to 300–500 kcal per day, will be offered to participants in the intervention group according to their nutritional status. The interventions according to the participants’ nutritional statuses are described below:
(1) Well-nourished: overall dietary assessment and possible correction.
(2) At risk of malnutrition: diet correction and consumption of up to two protein supplement packs per day.
(3) Malnourishment: diet correction and consumption of up to three protein supplement packs per day.
To improve compliance with the intervention, exercise and nutrition diaries will be provided to the participants. Additionally, biweekly telephone monitoring will be conducted to assess compliance by providing feedback to the intervention group. Participants will be provided a high-protein meal at a local restaurant, and a nutritionist will provide dietary education to the participants during the fourth week of the nutrition intervention. However, participants in the control group will receive biweekly telephone monitoring to prevent dropouts and check for medical issues. They will be given exercise–nutrition educational materials during their first visit and instructed to maintain their usual amount of activity and diet during the study period without additional exercise or nutrition interventions.
Outcomes measures
The outcomes will be measured before the intervention (baseline), during the intervention (6 weeks), immediately after the intervention (12 weeks), and 12 weeks after completing the intervention (at 24 weeks, which is the total study duration).
Primary outcomes
The primary outcome will be the 5-times chair stand test results. The test will be conducted before (baseline), during (6 weeks), and immediately after the intervention (12 weeks).
Secondary outcomes
The following secondary outcomes will be measured:
(1) Before (baseline) and immediately after the intervention (12 weeks): sarcopenic indices for possible sarcopenia (calf circumference, SARC-F questionnaire and 5-times chair stand test, handgrip strength); bioelectrical impedance analysis (BIA, depending on resources available in the local primary care clinic); MNA; the 12-item Health Survey; history of falls; psychiatric assessment (Korean Mini-Mental Status Examination, 2nd edition [range: 0–30; lower scores indicate a worse outcome] and Geriatric Depression Scale – Korea [range: 0–30; lower scores indicate a worse outcome]); and other comprehensive geriatric assessments (the Korean version of the Physical Activity Scale for the Elderly, Korean Instrumental Activities of Daily Living questionnaire [K-IADL; range: 0–3; higher scores indicates worse outcomes], and EuroQol Visual Analogue Scale [range: 0–1; lower scores indicate worse outcomes]).
(2) During the intervention (6 weeks): sarcopenic indices for possible sarcopenia (calf circumference, 5-times chair stand test, handgrip strength, and SARC-F questionnaire), BIA (depending on resources available in the local primary care clinic), and K-IADL scores.
(3) Twelve weeks after completing the intervention (telephone survey at 24 weeks): history of falls, Korean version of the Physical Activity Scale for the Elderly scores, Geriatric Depression Scale – Korea scores, and K-IADL scores (Table 1).
Table 1. Overview of the outcome measures for the trial according to the intervention time-points.
Abbreviations: SARC-F, strength, assistance with walking, rising from a chair, climbing stairs, and falls.
Period
|
Baseline
|
Intervention
|
Follow-up
|
Screening
|
Visit 1
|
Visit 2
|
Visit 3
|
Telephone call
|
Time-point
|
0-week
|
0-week
|
6-week
|
12-week
|
24-week
|
Day (days)
|
|
0
|
42
|
84
|
168
|
Visit window (days)
|
|
|
±10 d
|
±10 d
|
±14 d
|
Informed consent
|
●
|
|
|
|
|
Inclusion and exclusion criteria
|
●
|
|
|
|
|
Demographic data
|
●
|
|
|
|
|
Randomization
|
●
|
|
|
|
|
SARC-F
|
●
|
|
|
|
|
5-times chair stand test
|
●
|
|
●
|
|
|
Hand grip strength (hand-held dynamometer)
|
●
|
|
|
|
|
Calf circumference
|
●
|
|
|
|
|
Bioelectrical Impedance Analysis
(only if available)
|
●
|
|
●
|
●
|
●
|
Questionnaire about falls
|
|
●
|
|
|
●
|
Korean version of the Physical Activity Scale for the Elderly (K-PASE)
|
|
●
|
|
|
|
Mini-Nutritional Assessment (MNA)
|
|
●
|
|
|
|
Korean version of the Mini-Mental State Examination (K-MMSE)
|
|
●
|
|
|
|
Short Form of Geriatric Depression Scale-Korea (SGDS-K)
|
|
●
|
|
|
●
|
Korean Instrumental Activities of Daily Living (K-IADL)
|
|
●
|
|
|
●
|
EuroQol Visual Analogue Scale (EQ-VAS)
|
|
●
|
|
|
|
12-item Health Survey (SF-12)
|
|
●
|
●
|
●
|
|
Monitoring Sheet
|
|
|
|
|
●
|
Nutritional support service (4-week time-point)
|
|
|
|
|
|
Statistical analysis
Sample size determination
The target sample size for this study was determined based on a previous study that focused on improving muscle function (5-times chair stand test) through a three-month exercise–nutrition intervention among community-dwelling older adults [34]. According to previous findings, the change in the 5-times chair stand test performance over the three-month period was -3.77 ± 2.94 seconds and -1.49±3.17 seconds for the exercise–nutrition and control groups, respectively, with a group effect p-value of 0.004. The effect size was 0.75. With 90% power using G*Power, 78 participants (39 participants in the intervention and control groups each) were required. Considering a dropout rate of 20%, 94 eligible participants will be recruited from primary care clinics according to the established criteria.
Data analysis
Data will be collected and recorded using a data management system. The intention-to-treat and per-protocol principles will be implemented for data analysis. Participants undergoing baseline measurements and the first-week intervention will be included in the intention-to-treat analysis to compare pre- and post-intervention outcomes within each group. Two-way repeated measures ANOVA or Wilcoxon signed-rank test, and paired t-test will be conducted. In cases of study discontinuation or dropout, missing data will be reported using the Full Analysis Set method. Statistical significance will be defined as p<0.05. All statistical analyses will be performed using SPSS software (version 19.0; IBM, Armonk, New York, USA).