Boosting Exercise cApaCity With autOnomic Neuromodulation

Summary

Background: Exercise performance is a key predictor for healthy ageing. Laboratory and clinical data have shown strength of a nerve called the vagus nerve, which is lost during age-related disease processes, determines exercise performance. The investigators describe a study protocol designed to test the hypothesis that stimulation of the ear (where the vagus nerve can be safely stimulated) may improve exercise performance alongside beneficial changes in vagus nerve activity in human volunteers.

Methods. 28 healthy participants aged 18-75y will be randomly allocated to electrical ear stimulation or placebo treatment for 30 minutes at the same time of day, for 7 consecutive days. Heart monitoring, exercise bike testing, a simple sit-to-stand test and blood sampling will be performed immediately before the first day's intervention and after the last day's intervention. Participants and investigators will be masked to the treatment allocations and analyses. After a 14-day break, participants will perform the same protocol for the opposite intervention to their first treatment allocation. The primary outcome will be the change in VO2Peak (the best measure of exercise performance) following stimulation or placebo protocol. Secondary outcomes include reduction in heart rate after ending the exercise bike test, reduction from peak heart rate after standing from sitting, beat-to-beat heart rate measures and blood inflammatory marker levels. These outcomes will measure exercise performance and vagus nerve function. Safety and complications of the intervention will also be recorded. The study was approved by the NHS Research Ethics Committee (21/LO/0856).

Discussion. This 'first-in-man' study will explore whether non-invasive vagus nerve stimulation safely boosts exercise performance and/or vagus nerve activity using electrical ear stimulation, providing data for a device-based approach that may be broadly generalisable to improving health outcomes.

Conditions

• Aging
• Inflammation
• Cardiovascular Diseases

Interventions

DEVICE

Active Transauricular nerve stimulation

The first allocated intervention will be undertaken for 30 minutes. The electrode placement and stimulation parameters are described in the arm/group section. After the 30-minute intervention, day 1 of the protocol will be complete. The investigator will remain present in the room with the participant to ensure compliance and adherence to the protocol. The allocated intervention will then be repeated by the participant at a similar time of day for 7 consecutive days. The investigator will arrange video-calls with the participant whilst off-site to ensure ongoing compliance and adherence to the protocol. On the seventh day, participants return to the clinical research facility to take the final first allocated intervention. A 14-day rest period will follow. Then the participants will perform the same 7-day protocol for the opposite intervention to their first treatment allocation.

DEVICE

Sham transauricular nerve stimulation

Protocol as for active but sham ear leads are applied, unable to deliver current.

Sponsors & Collaborators

• National Institute for Health Research, United Kingdom

  collaborator OTHER_GOV

• British Heart Foundation

  collaborator OTHER

• Queen Mary University of London

  lead OTHER

Principal Investigators

• Gareth L Ackland, FRCA · Queen Mary University of London

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

CROSSOVER

Eligibility

Min Age

18 Years

Max Age

75 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2022-11-09

Primary Completion

2023-05-10

Completion

2023-05-10

Countries

• United Kingdom

Study Locations