Boosting Exercise cApaCity With autOnomic Neuromodulation

NCT05619107 | Completed DMC

• 1 other identifier: 299987
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief 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

Keywords

Neuromodulation; Exercise Training

Outcome Measures

Primary Outcomes (1)

• Change in peak volume of oxygen uptake (VO2peak)

  Gold standard measure of exercise capacity

  7 days

Secondary Outcomes (4)

• Change in heart rate recovery (HRR)

  7 days

• Change in decline from peak heart rate (PeakHRdecline) after standing from the sitting position

  7 days

• Change in heart rate variability (HRV)

  7 days

• Change in plasma acetylcholine levels (PlasmaACh)

  7 days

Study Arms (2)

Active transauricular nerve stimulation

ACTIVE COMPARATOR

Using a training device, two conductive clips are placed securely on both the left and right tragus areas of the outer ear. Using parameters we have identified through systematic review, electrical stimulation (pulse width:200μs; frequency:30Hz) is initiated at 10mA, until the participant feels a 'tingling' sensation within 20s of commencing. At this point the current is reduced to a level just below this perceptible threshold (20-60 mA), which is defined as the 'prescription dose'. The participant then receives another active device set at the 'prescription dose'.

Device: Active Transauricular nerve stimulation

Sham transauricular nerve stimulation

SHAM COMPARATOR

Using a training device, two conductive clips are placed securely on both the left and right tragus areas of the outer ear. Using parameters we have identified through systematic review, electrical stimulation (pulse width:200μs; frequency:30Hz) is initiated at 10mA, until the participant feels a 'tingling' sensation within 20s of commencing (Figure 2). At this point the current is reduced to a level just below this perceptible threshold (20-60 mA), which is defined as the 'prescription dose'. The participant then receives another device set at the 'prescription dose' but this sham device is disabled from delivering any current .

Device: Sham transauricular nerve stimulation

Interventions

Active Transauricular nerve stimulation DEVICE

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.

Active transauricular nerve stimulation

Sham transauricular nerve stimulation DEVICE

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

Sham transauricular nerve stimulation

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-75y
• Male or female
• Able and willing to give informed consent

You may not qualify if:

• Current smoker
• Currently undertaking a dedicated training/exercise regime (i.e. not sedentary)
• Excess alcohol intake (as determined via a medical questionnaire)
• Contraindications to cardiopulmonary exercise testing
• Pregnancy
• Auricular dermatitis
• Unwilling or unable to give consent
• Inability to understand written and/or verbal English

Sponsors & Collaborators

• Queen Mary University of London: lead
• National Institute for Health Research, United Kingdom: collaborator
• British Heart Foundation: collaborator

Study Sites (1)

William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, John Vane Science Centre, Charterhouse Square

London, EC1M 6BQ, United Kingdom

Location

Related Publications (2)

• Machhada A, Trapp S, Marina N, Stephens RCM, Whittle J, Lythgoe MF, Kasparov S, Ackland GL, Gourine AV. Vagal determinants of exercise capacity. Nat Commun. 2017 May 18;8:15097. doi: 10.1038/ncomms15097.

  PMID: 28516907 BACKGROUND

• Gourine AV, Ackland GL. Cardiac Vagus and Exercise. Physiology (Bethesda). 2019 Jan 1;34(1):71-80. doi: 10.1152/physiol.00041.2018.

  PMID: 30540229 BACKGROUND

MeSH Terms

Conditions

Inflammation; Cardiovascular Diseases

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Gareth L Ackland, FRCA

  Queen Mary University of London

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participants and investigators are blinded to treatment allocations throughout data collection and analysis. Participants and investigators are also masked to the outcomes data, which will be analysed offline by an independent trial statistician not involved with patient recruitment/device application who is masked to the treatment allocations.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Double-blind, open crossover, randomised sham-controlled trial

Study Record Dates

• First Submitted: October 18, 2022
• First Posted: November 16, 2022
• Study Start: November 9, 2022
• Primary Completion: May 10, 2023
• Study Completion: May 10, 2023
• Last Updated: August 2, 2023

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)