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

Hypertension Clinical Trial

— RIPCo  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05971407
• Other study ID #: FMHS 34-0722
• Status: Recruiting
• Phase: N/A
• Start date: September 25, 2022
• Est. completion date: October 31, 2024

Study information

• Verified date: November 2023
• Source: University of Nottingham
• Contact: Harry G Keevil, MB BChir
• Phone: 01332 724687
• Email: harry.keevil[@]nottingham.ac.uk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: October 31, 2024
• Est. primary completion date: October 31, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 65 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Hypertension
• Vascular Diseases

Intervention

Device:
• Remote Ischaemic Preconditioning
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.
• Sham Remote Ischaemic Preconditioning
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.

Locations

Country	Name	City	State
United Kingdom	School of Medicine, Royal Derby Hospital Site, University of Nottingham	Derby	Derbyshire

Sponsors (1)

Lead Sponsor	Collaborator
University of Nottingham

Country where clinical trial is conducted

United Kingdom, 

References & Publications (6)

Baffour-Awuah B, Dieberg G, Pearson MJ, Smart NA. The effect of remote ischaemic conditioning on blood pressure response: A systematic review and meta-analysis. Int J Cardiol Hypertens. 2021 Feb 23;8:100081. doi: 10.1016/j.ijchy.2021.100081. eCollection 2021 Mar. — View Citation

Guthrie B, Makubate B, Hernandez-Santiago V, Dreischulte T. The rising tide of polypharmacy and drug-drug interactions: population database analysis 1995-2010. BMC Med. 2015 Apr 7;13:74. doi: 10.1186/s12916-015-0322-7. — View Citation

Health matters: combating high blood pressure: Public Health England; 2017

https://www.stroke.org.uk/what-is-stroke/stroke-statistics

Pirmohamed M, James S, Meakin S, Green C, Scott AK, Walley TJ, Farrar K, Park BK, Breckenridge AM. Adverse drug reactions as cause of admission to hospital: prospective analysis of 18 820 patients. BMJ. 2004 Jul 3;329(7456):15-9. doi: 10.1136/bmj.329.7456.15. — View Citation

Virani SS, Alonso A, Aparicio HJ, Benjamin EJ, Bittencourt MS, Callaway CW, Carson AP, Chamberlain AM, Cheng S, Delling FN, Elkind MSV, Evenson KR, Ferguson JF, Gupta DK, Khan SS, Kissela BM, Knutson KL, Lee CD, Lewis TT, Liu J, Loop MS, Lutsey PL, Ma J, Mackey J, Martin SS, Matchar DB, Mussolino ME, Navaneethan SD, Perak AM, Roth GA, Samad Z, Satou GM, Schroeder EB, Shah SH, Shay CM, Stokes A, VanWagner LB, Wang NY, Tsao CW; American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee. Heart Disease and Stroke Statistics-2021 Update: A Report From the American Heart Association. Circulation. 2021 Feb 23;143(8):e254-e743. doi: 10.1161/CIR.0000000000000950. Epub 2021 Jan 27. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	24-hour systolic blood pressure	Changes in blood pressure measured by 24-hour blood pressure monitor.	Measured at baseline and week 6
Secondary	24-hour diastolic blood pressure	Changes in blood pressure measured by 24-hour blood pressure monitor.	Measured at baseline and week 6
Secondary	24-hour mean arterial pressure	Changes in blood pressure measured by 24-hour blood pressure monitor.	Measured at baseline and week 6
Secondary	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
Secondary	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
Secondary	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.