Increasing Plasma Adrenaline Levels Through Breathing Techniques - an Explorative Study

NCT02417155 | Completed

• 1 other identifier: INADRI
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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.

Conditions

Autoimmune Diseases

Keywords

Autonomic Nerve System; Epinephrin; Hyperventilation; Hypoventilation

Outcome Measures

Primary Outcomes (1)

• Concentration of plasma adrenaline within arm 1

  Our primary endpoint is the difference between plasma adrenaline levels during the hyper/hypoventilation technique and the strength ventilation technique within the HTR group.

  1 day

Secondary Outcomes (11)

• Concentration of plasma adrenaline within arms 2, 3, 4

  1 day

• concentration of plasma adrenaline between arms 1, 2, 3, 4

  1 day

• Plasma interleukine 10 concentration

  1 day

• Body temperature

  1 day

• Heart rate, blood pressure

  1 day

Study Arms (4)

HTR

EXPERIMENTAL

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.

Behavioral: Hyper/hypoventilation; Behavioral: Strength ventilation

EIN

ACTIVE COMPARATOR

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.

Behavioral: Hyper/hypoventilation; Behavioral: Strength ventilation

STR

ACTIVE COMPARATOR

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.

Behavioral: Hyper/hypoventilation; Behavioral: Strength ventilation

SIN

ACTIVE COMPARATOR

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.

Behavioral: Hyper/hypoventilation; Behavioral: Strength ventilation

Interventions

Hyper/hypoventilation BEHAVIORAL

Subjects are asked to hyperventilate for an average of 30 breaths. Subsequently, the subjects exhaled and hold their breath for approximately 2 minutes ("retention phase"). The duration of breath retention will be entirely at the discretion of the subject himself. Breath retention is followed by a deep inhalation breath, that will be held for 10 s. Subsequently a new cycle of hyper/hypoventilation begins.

EIN; HTR; SIN; STR

Strength ventilation BEHAVIORAL

This exercise consists of deep inhalations and exhalations in which every inhalation and exhalation is followed by breath holding for 10 s, during which the subject tightens all his body muscles.

EIN; HTR; SIN; STR

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Radboud University Medical Center: lead

Study Sites (1)

Intensive Care Medicine, Radboud University Nijmegen Medical Centre

Nijmegen, Gelderland, 6500 HB, Netherlands

Location

Related Publications (3)

• 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.

  PMID: 24799686 BACKGROUND

• 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.

  PMID: 22685240 BACKGROUND

• 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.

  PMID: 35213875 DERIVED

MeSH Terms

Conditions

Autoimmune Diseases; Hyperventilation; Hypoventilation

Condition Hierarchy (Ancestors)

Immune System Diseases; Respiration Disorders; Respiratory Tract Diseases; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Respiratory Insufficiency

Study Officials

• Matthijs Kox, PhD

  Radboud University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 2, 2014
• First Posted: April 15, 2015
• Study Start: November 1, 2014
• Primary Completion: July 1, 2015
• Study Completion: October 1, 2015
• Last Updated: November 10, 2015

Record last verified: 2015-11

Locations

NL (1)