Effectiveness of an Endurance Exercise Programme Preceded by Ischaemic Preconditioning in Older People

Study Overview
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Brief Summary
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In recent decades, the proportion of people over 65 years of age is increasing rapidly, due to rising life expectancy and declining fertility rates. According to the World Health Organization, people in this age group will constitute 22% of the population by 2050, up from the current 12% (WHO, 2018). Therefore, improving quality of life (healthspan) and preventing disability has become a public health challenge (Olshansky, 2018). In this context, physical exercise has been shown to be able to prevent sarcopenia, functional decline, the presence of chronic diseases and even mortality in this group (Izquierdo et al., 2021; Lazarus, Lord, & Harridge, 2019). A training method that could enhance the benefits of walking is ischaemic preconditioning (IPC), characterised by the application of brief periods of circulatory occlusion-reperfusion to a limb, minutes to hours prior to exercise. This type of intervention, initially used to delay/prevent cell damage in patients with myocardial infarction (Murry, Jennings, & Reimer, 1986), has recently shown beneficial effects in young people to improve physical performance in a wide variety of sports (Caru, Levesque, Lalonde, & Curnier, 2019), as well as to improve recovery from associated muscle damage (Franz et al., 2018), which is of particular interest in the adult population. In fact, the application of IPC alone for two weeks has been shown to improve walking speed and reduce fatigue in post-stroke patients (Durand et al., 2019), promising effects that could be increased when applied prior to resistance training, such as walking. Thus, the objective of this study is to determine the effectiveness of an endurance exercise programme preceded by ischaemic preconditioning on parameters related to physical function, cognitive status and quality of life in older people. In addition, we set out to compare the acute and chronic effect of the proposed interventions.

Detailed Description
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In recent decades, the proportion of people over 65 years of age is increasing rapidly, due to rising life expectancy and declining fertility rates. According to the World Health Organization, people in this age group will constitute 22% of the population by 2050, up from the current 12% (WHO, 2018). Therefore, improving quality of life (healthspan) and preventing disability has become a public health challenge (Olshansky, 2018). In this context, physical exercise has been shown to be able to prevent sarcopenia, functional decline, the presence of chronic diseases and even mortality in this group (Izquierdo et al., 2021; Lazarus, Lord, & Harridge, 2019). Resistance or endurance training can improve sarcopenia, reduce intramuscular fat accumulation, improve muscle function, among others. Aerobic exercise has been shown to be effective in maintaining muscle mass and strength in older adults is walking (Kubo et al., 2008). In fact, walking can also improve VO2max in older adults when intensities are above ∼40% VO2max (Nemoto, Gen-no, Masuki, Okazaki, & Nose, 2007). In addition, it has been linked to the prevention of cognitive decline (Maki et al., 2012) and improvements in quality of life (Awick et al., 2015) in older people. A training method that could enhance the benefits of walking is ischaemic preconditioning (IPC), characterised by the application of brief periods of circulatory occlusion-reperfusion to a limb, minutes to hours prior to exercise. This type of intervention, initially used to delay/prevent cell damage in patients with myocardial infarction (Murry, Jennings, & Reimer, 1986), has recently shown beneficial effects in young people to improve physical performance in a wide variety of sports (Caru, Levesque, Lalonde, & Curnier, 2019), as well as to improve recovery from associated muscle damage (Franz et al., 2018), which is of particular interest in the adult population. In fact, the application of IPC alone for two weeks has been shown to improve walking speed and reduce fatigue in post-stroke patients (Durand et al., 2019), promising effects that could be increased when applied prior to resistance training, such as walking. Thus, the objective of this study is to determine the effectiveness of an endurance exercise programme preceded by ischaemic preconditioning on parameters related to physical function, cognitive status and quality of life in older people. In addition, we set out to compare the acute and chronic effect of the proposed interventions. Therefore, this study is a randomized clinical trial in which three groups of twenty people in each group will participate, with different interventions: Experimental group 1: Exercise protocol + IPC. Experimental group 2: Exercise protocol + sham IPC. Control group. Participants will be evaluated in four moments, at baseline, immediately after the first session, postintervention (after 6-week intervention) and 4-week follow-up. Data analysis will be performed with SPSS statistic program (v26). Normality and homoscedasticity will be analyzed by Shapiro-Wilk t-test and Levene test, respectively. For comparation between groups Bonferroni will be used. If any confusion factor that not meet requirements to be analysed like a covariable exist, ANCOVA will be used. When p<0.0.5 statistical significant differences will be assumed.

Official Title
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Effectiveness of an Endurance Exercise Programme Preceded by Ischaemic Preconditioning in Older People: a Randomised Clinical Trial

Conditions
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Older People

Intervention / Treatment
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* Other: Exercise protocol + IPC
* Other: Exercise protocol + Sham IPC


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 65 -90 years Physically inactive (< 150 minutes of physical activity per week). Signed informed consent form Exclusion Criteria: Institutionalised patients. History of stroke in the last 6 months or hospital admission for any reason in the last 3 months. Uncontrolled hypertension. Medication with anticoagulants. Oncological patient with active treatment: chemotherapy or radiotherapy. Neurological or cardiovascular musculoskeletal pathology that contraindicates physical activity. Cognitive impairment (score below 25 on the Mini-mental Test); or severe disability (score below 15 points on the Barthel scale). Completion of less than 80% of training sessions.

Ages Eligible for Study
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Minimum Age: 65 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Exercise protocol + IPC group<br>Patients in this group (n=17) will undergo an endurance training protocol. Prior to this training (8-12 minutes before) they will undergo ischaemic preconditioning. | Other: Exercise protocol + IPC<br>* Exercise protocol: endurance training protocol consisting of walking 20 min at moderate intensity (i.e. 64- 76 % HRmax, 12-13 Borg Scale) in a circuit designed in an open field, 3 times a week, for 6 weeks. IPC: participants will be placed in a supine position and a pneumatic compression cuff (Riester Komprimeter, Jungingen Germany) (96 centimetres long x 13 centimetres wide) will be placed on the proximal part of each lower extremity. Occlusion will then be performed by inflating the cuff to 220 mmHg for 5 minutes, followed by reperfusion to 0 mmHg for 5 minutes. Each session will consist of 3 sets of 5 minutes of ischaemia followed by 5 minutes of reperfusion.<br>|
| Sham Comparator: Exercise protocol + Sham IPC group<br>Patients in this group (n=17) will undergo the same training as the previous group and with the same frequency and duration, but the pressure cuff will be inflated by only 10 mmHg, so that it will act as a placebo. | Other: Exercise protocol + Sham IPC<br>* Patients in this group (n=20) will undergo the same training as the previous group and with the same frequency and duration (i.e. 3 times a week, for 6 weeks), but the pressure cuff will be inflated by only 10 mmHg, so that it will act as a placebo.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiorespiratory fitness | 6 minutes walking test (6MWT) | 8 minutes | 
| Heart rate variability during walking | Heart rate monitor RS800CX (Polar Electro Oy Kempele, Finland). | 40 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lower limb strength: for the assessment of isometric strength | A load cell (CTCS; Mutronic) will be used to measure the strength of the intrinsic and extrinsic muscles of the hip, knee and ankle | 10 minutes | 
| Muscle mass (sacopenia) | Bioimpedance (Tanita DC-430MA, Tanita Corporation of America, Inc., Arlington Heights, IL, USA). | 3 minutes | 
| General physical condition | Short Physical Performance Battery | 5 minutes | 
| Fatigue | Borg scale 20 | 1 minute | 
| Fall risk, agility and dynamic balance | Fall skip | 3 minutes | 
| Independence in basic activities of daily living (BADL) and instrumental activities of daily living (IADL) | Barthel Index and Lawton and Brody scale, respectively | 5 minutes | 
| Health-related Quality of Life | EQ-5D-5L | 2 minutes |