The Effect of Chronic Remote Ischaemic Preconditioning on Blood Pressure in Older Adults

Study Overview
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Brief Summary
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The purpose of this study is to assess whether remote ischaemic conditioning, applied chronically, improves vascular health in older adults

Detailed Description
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Hypertension and stroke remain leading causes of mortality across the world (1). Hypertension affects more than 1 in 4 adults and is the 3rd biggest risk factor for premature death and disability in the UK (2). Cerebrovascular disease is ranked 4th in the list of leading causes of death in the UK (3). At present, the treatment of these conditions largely involves chronic pharmacotherapy. In parallel, it is increasingly appreciated that polypharmacy poses a significant challenge to our older adult population. Guthrie et al showed that the number of people prescribed >5 medications in an area of the UK doubled between 1995 and 2010 (from 11.4% to 20.8%) (4). Age is significantly associated with polypharmacy, with an odds ratio of 118.3 when those aged 20-29 are compared to those >80. What's more, it has been estimated that adverse drug reactions account for 6.5% of hospital admissions (5), with age correlating significantly with admissions for this reason. Therefore, discovering a non-pharmacological intervention for hypertension and cerebrovascular disease could greatly benefit the population, particularly the elderly, both in terms of treating the diseases themselves and reducing the harmful effects of polypharmacy. Remote ischaemic preconditioning (RIPC) is the induction of non-lethal ischaemia in one organ or tissue, with the aim of conditioning a distant organ or tissue against ischaemic events. It is achieved via inflation of a blood pressure cuff to supra-systolic pressures for a short period of time. A recent meta-analysis showed that chronic RIC, but not acute RIC, significantly lowered diastolic and mean arterial blood pressure (6). The studies included in this review were small and performed in a younger population, hence larger studies are needed to clarify the effect of RIC in the field of hypertension and, importantly, the elderly.

Official Title
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The Effect of Chronic Remote Ischaemic Preconditioning on Blood Pressure in Older Adults

Conditions
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Hypertension, Vascular Diseases

Intervention / Treatment
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* Device: Remote Ischaemic Preconditioning
* Device: Sham Remote Ischaemic Preconditioning


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant is aged >65y and <85y. Participant is willing and able to give informed consent for participation in the study. Participant is physically able to perform RIPC. Exclusion Criteria: A BMI <18 or >35 kg/m2 Active cardiovascular, cerebrovascular or respiratory disease: e.g. uncontrolled hypertension (BP > 160/100), active angina, heart failure (class III/IV), arrhythmia, right to left cardiac shunt, recent cardiac event, COPD, pulmonary hypertension or recent (6 mo) stroke. If history of hypertension, no recent alteration to antihypertensive medication (3 months). A history of, or current neurological or musculoskeletal conditions (e.g. epilepsy) Having taken part in a research study in the last 3 months involving invasive procedures or an inconvenience allowance

Ages Eligible for Study
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Minimum Age: 65 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Participants complete a 6-week intervention period during which the participants receive either RIPC or sham. There is then a 6-week washout period, after which participants complete the other intervention
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Remote Ischaemic Preconditioning<br>RIPC is induced by 4 cycles of 5 minutes of healthy upper limb ischaemia followed by 5 minutes reperfusion. Ischaemia is induced by inflation of a blood pressure cuff to 20mmHg above systolic blood pressure. RIPC is conducted 3 times weekly for 6-weeks. | Device: Remote Ischaemic Preconditioning<br>* RIPC is induced by 4 cycles of 5 minutes of healthy upper limb ischaemia followed by 5 minutes reperfusion. Ischaemia is induced by inflation of a blood pressure cuff to 20mmHg above systolic blood pressure. RIPC is conducted 3 times weekly for 6-weeks. Clinic blood pressure is measured at weeks 0, 3 and 6. 24-hour blood pressure is measured at weeks 0 and 6.<br>|
| Sham Comparator: Sham remote ischaemic preconditioning<br>Sham RIPC is induced by 4 cycles of 5 minutes of healthy upper limb ischaemia followed by 5 minutes reperfusion. Ischaemia is induced by inflation of a blood pressure cuff to 20mmHg. RIPC is conducted 3 times weekly for 6-weeks | Device: Sham Remote Ischaemic Preconditioning<br>* Sham RIPC is induced by 4 cycles of 5 minutes of healthy upper limb ischaemia followed by 5 minutes reperfusion. Ischaemia is induced by inflation of a blood pressure cuff to 20mmHg. RIPC is conducted 3 times weekly for 6-weeks. Clinic blood pressure is measured at weeks 0, 3 and 6. 24-hour blood pressure is measured at weeks 0 and 6.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinic systolic blood pressure | Changes in blood pressure measured by automated sphygmomanometer over 6 weeks. Measured after participants have rested for 10 minutes in a temperature controlled room. | Measured at baseline, week 3 and week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinic diastolic blood pressure | Changes in blood pressure measured by automated sphygmomanometer over 6 weeks. Measured after participants have rested for 10 minutes in a temperature controlled room. | Measured at baseline, week 3 and week 6 | 
| Clinic Mean arterial pressure | Changes in blood pressure measured by automated sphygmomanometer over 6 weeks. Measured after participants have rested for 10 minutes in a temperature controlled room. | Measured at baseline, week 3 and week 6 | 
| 24-hour systolic blood pressure | Changes in blood pressure measured by 24-hour blood pressure monitor. | Measured at baseline and week 6 | 
| 24-hour diastolic blood pressure | Changes in blood pressure measured by 24-hour blood pressure monitor. | Measured at baseline and week 6 | 
| 24-hour mean arterial pressure | Changes in blood pressure measured by 24-hour blood pressure monitor. | Measured at baseline and week 6 | 
| Flow mediated dilatation (FMD) | Flow mediated dilatation is measured by continuous ultrasound imaging of the brachial artery. Brachial artery diameter is measured using edge tracking software for one minute before distal occlusion is applied to the brachial artery for 5 minutes at 230mmHg using and automated vascular assessment pressure cuff. Following release of the distal occlusion, flow mediated dilatation is measured for 4 minutes using edge tracking software | Measured at baseline, week 3 and week 6 | 
| Pulsewave velocity (PWV) | Pulsewave velocity is measured using carotid and femoral artery transducers. Pulse transit time and the distance between transducers is then used to calculate PWV. | Measured at baseline, week 3 and week 6 | 
| Serum biomarkers | Biomarkers of RIC mechanism will be quantified by ELISA from plasma samples collected before and after intervention. | Measured at baseline and week 6. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Remote Ischaemic Preconditioning, Non-pharmacological, Remote Ischaemic Conditioning, Randomised Controlled Trial