Clinical trial NCT05623696: Effect of Non-invasive Magnetic Stimulation of the Brain on Breathlessness in Healthy Individuals.
Official title: Effect of Repetitive Transcranial Magnetic Stimulation (rTMS) of the Dorsolateral Prefrontal Cortex (DLPFC) on Hypercapnic Air Hunger Induced in Healthy Individuals.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Dyspnea
Keywords: Air Hunger
Lead sponsor: Oxford Brookes University
Sponsor class: OTHER
Collaborators: name: University of Oxford
First posted: 2022-11-21
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Following a practice session, there will be 3 intervention arms presented in random order on 3 separate days. The three arms will be: (i) 10-20mins of 5Hz rTMS over left DLPFC (Arm 1), (ii) 5Hz rTMS over right DLPFC (Arm 2), (iii) sham rTMS (Arm 3). A standard steady state air hunger test will be conducted before and immediately after each intervention.
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of this study is to see if the front part of the brain called the "Dorsolateral Prefrontal Cortex" (DLPFC) has a role in our ability to feel breathlessness. The experiment will use a device that sits on the top of the head which produces a magnetic field that penetrates the scalp and excites the brain tissue directly under it. This procedure is called repetitive transcranial magnetic stimulation (rTMS), it is a painless procedure and known to be safe in healthy individuals. Previous research has shown that the pain felt when capsaicin, the active ingredient in 'chilli' powder, is applied to the hand is reduced by applying the rTMS on the scalp directly above the DLPFC part of the brain. In this experiment we want to see if breathlessness is also reduced. We will use a breathing task that will generate a moderate amount of breathlessness by adding a small amount of carbon dioxide to the inhaled air, while preventing the increase in the amount of breathing we would normally see in response to this. If we find that breathlessness produced by this breathing task is reduced after rTMS over the DLPFC, this may lead to new drugs that target this part of the brain in patients suffering from breathlessness due to heart or lung disease. The study will also improve our knowledge of how the brain enables us to feel breathlessness


Eligibility criteria: Inclusion Criteria:

healthy individuals, over 18 years old, with no history of heart, lung or neurological conditions

Exclusion Criteria:

* Any history of respiratory problems (including Asthma that involves regular use of inhalers)
* Any history of heart or circulatory problems (e.g. palpitations, arrhythmias, angina, BP)
* Any history of epilepsy, convulsions or seizures, migraines, or fainting
* Any history of anxiety disorders (e.g. panic attacks)
* Any history of serious head injury or brain surgery
* Any metal parts in the head (except dental wire)
* Any implants (e.g. pacemaker, insulin pump, neurostimulator)
* Pregnancy or problems with alcohol or drug abuse.

Primary outcomes:
measure: Air hunger
timeFrame: Average of 4 steady state ratings in the last minute of air hunger tests
Secondary outcomes:
measure: Mood assessment
timeFrame: immediately following pre and post intervention air hunger tests
measure: Trait and state anxiety scores
timeFrame: immediately following pre and post intervention air hunger tests
measure: Dyspnoea-12 total, physical and emotion scores
timeFrame: Administered immediately following pre and post intervention air hunger tests in relation to the "test just completed"
Other outcomes:
Locations:
city: Oxford
country: United Kingdom
facility: Oxford Brookes University
state: Oxfordshire
Study officials:
affiliation: Oxford Brookes University
name: Shakeeb H Moosavi, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Banzett RB, Moosavi SH. Dyspnea and pain: Similarities and contrasts between two very unpleasant sensations. APS Bulletin. 2001; 11: 1-8.
citation: Brighina F, De Tommaso M, Giglia F, Scalia S, Cosentino G, Puma A, Panetta M, Giglia G, Fierro B. Modulation of pain perception by transcranial magnetic stimulation of left prefrontal cortex. J Headache Pain. 2011 Apr;12(2):185-91. doi: 10.1007/s10194-011-0322-8. Epub 2011 Feb 25.
citation: Harrison OK, Hayen A, Wager TD, Pattinson KTS. Investigating the specificity of the neurologic pain signature against breathlessness and finger opposition. Pain. 2021 Dec 1;162(12):2933-2944. doi: 10.1097/j.pain.0000000000002327.
citation: Herigstad M, Hayen A, Evans E, Hardinge FM, Davies RJ, Wiech K, Pattinson KTS. Dyspnea-related cues engage the prefrontal cortex: evidence from functional brain imaging in COPD. Chest. 2015 Oct;148(4):953-961. doi: 10.1378/chest.15-0416.
citation: Nierat MC, Hudson AL, Chaskalovic J, Similowski T, Laviolette L. Repetitive transcranial magnetic stimulation over the supplementary motor area modifies breathing pattern in response to inspiratory loading in normal humans. Front Physiol. 2015 Sep 29;6:273. doi: 10.3389/fphys.2015.00273. eCollection 2015.
citation: Yorke J, Moosavi SH, Shuldham C, Jones PW. Quantification of dyspnoea using descriptors: development and initial testing of the Dyspnoea-12. Thorax. 2010 Jan;65(1):21-6. doi: 10.1136/thx.2009.118521. Epub 2009 Dec 8.