Increasing Plasma Adrenaline Levels Through Breathing Techniques - an Explorative Study (INADRI)

Radboud University Medical Center

Status: Completed

Conditions: Autoimmune Diseases

Treatments: Behavioral: Strength ventilation; Behavioral: Hyper/hypoventilation

Study type: Interventional

Funder types: Other

Identifiers

NCT02417155

INADRI

Details and patient eligibility

About

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.

Full 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.

Enrollment: 40 patients

Sex: Male

Ages: 18 to 35 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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40 participants in 4 patient groups

HTR

Experimental group

Description:

The 'Hoftraining' group (HTR): a group of subjects (n=10) that will be trained extensively by mr. Hof and his team in both hyper/hypoventilation and strength ventilation breathing techniques. Total time training is 8 days.

Treatment:

Behavioral: Strength ventilation

Behavioral: Hyper/hypoventilation

EIN

Active Comparator group

Description:

The 'extensive instruction' group (EIN): a group of subjects (n=10) that will receive an extensive instruction course supervised by the research team (in absence of Mr. Hof) in both hyper/hypoventilation and strength ventilation breathing techniques.

Treatment:

Behavioral: Strength ventilation

Behavioral: Hyper/hypoventilation

STR

Active Comparator group

Description:

The 'short training' group (STR): a group of subjects (n=10) that will receive only a short training of 1 hour (immediately prior to the study) by Mr. Hof and his team in both hyper/hypoventilation and strength ventilation breathing techniques.

Treatment:

Behavioral: Strength ventilation

Behavioral: Hyper/hypoventilation

SIN

Active Comparator group

Description:

The 'short instruction' group (SIN): a group of subjects (n=10) that will receive no training, but only an short instruction course of 1 hour (immediately prior to the study) supervised by the research team (in absence of Mr. Hof) in both hyper/hypoventilation and strength ventilation breathing techniques.

Treatment:

Behavioral: Strength ventilation

Behavioral: Hyper/hypoventilation