Clinical trial NCT02417155: Increasing Plasma Adrenaline Levels Through Breathing Techniques - an Explorative Study
Official title: Increasing Plasma Adrenaline Levels Through Breathing Techniques - an Explorative Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Autoimmune Diseases
Keywords: Autonomic Nerve System
Epinephrin
Hyperventilation
Hypoventilation
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
First posted: 2015-04-15
Enrollment: 40
Sex: MALE
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: Inflammatory cytokines play a pivotal role in rheumatoid arthritis (RA) and innovative non-pharmacological therapies aimed at limiting cytokine production are highly warranted. Adrenaline, a neurotransmitter of the autonomic sympathetic nervous system, attenuates cytokine production. Along these lines, endogenous modulation of sympathetic activity could limit inflammation and therefore represent a treatment modality that would empower RA patients to exert self-control over disease activity. However, both the autonomic nervous system and the inflammatory response are regarded as systems that cannot be voluntarily influenced. Nevertheless, results from two recent studies demonstrate that this is possible through techniques developed by 'iceman' Wim Hof, namely meditation, exposure to cold, and breathing exercises. Hof himself and healthy volunteers trained by him were able to voluntarily activate the sympathetic nervous system, resulting in adrenaline release and subsequent suppression of the inflammatory response during experimental human endotoxemia (a model of systemic inflammation elicited by administration of lipopolysaccharide \[LPS\] in healthy volunteers). Interestingly, while having been taught all three techniques, during the endotoxemia experiment the trained subjects (like Hof himself) predominantly practiced the breathing exercises consisting of two different techniques. A 'hyper/hypoventilation' technique, characterized by cycles of hyperventilation followed by breath retention and a 'strength ventilation' technique consisting of deep inhalations and exhalations followed by breath holding. These techniques resulted in intermittent hypoxia and cyclic shifts in acid-base balance. Based on these observations and previous studies, the investigators hypothesize that these breathing techniques account for the increased production of adrenaline and thus for the suppressed inflammatory response but it is unclear which of these two techniques is most important.

Detailed description: The main objective of the study is to compare the increase in plasma adrenaline levels during the two different breathing techniques in a group of healthy volunteers trained by Hof. Also, the investigators investigate whether it is necessary to be trained by Hof and if a relatively short instruction instead of the extensive training is sufficient. Additionally, the investigators want to evaluate the influence of the training and breathing techniques on pain thresholds.

Eligibility criteria: Inclusion Criteria:

* Age ≥18 and ≤35 yrs
* Male
* Healthy

Exclusion Criteria:

* Experience with the methods of Wim Hof or other breathing techniques
* Use of any medication
* Smoking
* Use of recreational drugs within 21 days prior to the experiment day
* Use of caffeine or alcohol within 1 day prior to the experimental day.
* Surgery or trauma with significant blood loss or blood donation within 3 months prior to the experimental day.
* Participation in another clinical trial within 3 months prior to the experimental day.
* History, signs, or symptoms of cardiovascular disease
* History of atrial or ventricular arrhythmia
* Hypertension (RR systolic \>160 or RR diastolic \>90)
* Hypotension (RR systolic \<100 or RR diastolic \<50)
* Conduction abnormalities on the ECG consisting of a 1st degree atrioventricular block or a complex bundle branch block
* History of asthma, or any other pulmonary disease
* C reactive protein (CRP) \> 20 mg/L, White blood count (WBC) \> 12x109/L, or clinically significant acute illness, including infections, within 4 weeks before the experimental day.

Primary outcomes:
measure: Concentration of plasma adrenaline within arm 1
timeFrame: 1 day
Secondary outcomes:
measure: Concentration of plasma adrenaline within arms 2, 3, 4
timeFrame: 1 day
measure: concentration of plasma adrenaline between arms 1, 2, 3, 4
timeFrame: 1 day
measure: Plasma interleukine 10 concentration
timeFrame: 1 day
measure: Body temperature
timeFrame: 1 day
measure: Heart rate, blood pressure
timeFrame: 1 day
measure: Blood pressure
timeFrame: 1 day
measure: Leukocyte counts and differentiation
timeFrame: 1 day
measure: Cortisol (plasma)
timeFrame: 1 day
measure: Noradrenaline
timeFrame: 1 day
measure: Blood gas parameters
timeFrame: 1 day
measure: Pain threshold
timeFrame: 1 day
Other outcomes:
Locations:
city: Nijmegen
country: Netherlands
facility: Intensive Care Medicine, Radboud University Nijmegen Medical Centre
state: Gelderland
Study officials:
affiliation: Radboud University Medical Center
name: Matthijs Kox, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kox M, van Eijk LT, Zwaag J, van den Wildenberg J, Sweep FC, van der Hoeven JG, Pickkers P. Voluntary activation of the sympathetic nervous system and attenuation of the innate immune response in humans. Proc Natl Acad Sci U S A. 2014 May 20;111(20):7379-84. doi: 10.1073/pnas.1322174111. Epub 2014 May 5.
citation: Kox M, Stoffels M, Smeekens SP, van Alfen N, Gomes M, Eijsvogels TM, Hopman MT, van der Hoeven JG, Netea MG, Pickkers P. The influence of concentration/meditation on autonomic nervous system activity and the innate immune response: a case study. Psychosom Med. 2012 Jun;74(5):489-94. doi: 10.1097/PSY.0b013e3182583c6d.
citation: Zwaag J, Naaktgeboren R, van Herwaarden AE, Pickkers P, Kox M. The Effects of Cold Exposure Training and a Breathing Exercise on the Inflammatory Response in Humans: A Pilot Study. Psychosom Med. 2022 May 1;84(4):457-467. doi: 10.1097/PSY.0000000000001065. Epub 2022 Feb 23.