Concentration/Meditation Limits Inflammation

Study Overview
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Brief Summary
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Auto-immune diseases are characterized by an inappropriate inflammatory response against tissues in the body and represent a major health care burden. Pro-inflammatory cytokines such as TNF-α, IL-6 and IL-1β play a central role in the pathophysiology of many auto-immune diseases. Innovative therapies aimed at limiting pro-inflammatory cytokine production in a more physiological manner are warranted. In previous research conducted in an individual known as the iceman, the investigators found that, through a autodidact concentration/meditation technique, he appears to mount a controlled stress response, characterized by activation of the sympathetic nervous system and enhanced production of cortisol, both of which are known to result in immunosuppression. In accordance, while practicing this concentration/meditation technique, the inflammatory response during human endotoxemia (lipopolysaccharide [LPS] administration) was remarkably low in this individual. Therefore, this technique could provide a novel means of controlling the inflammatory response. However, the aforementioned results were obtained in just one subject, and hence can not serve as scientific evidence for the effectiveness of the concentration/meditation technique. The iceman claims that he can teach this technique to other subjects within a relatively short time frame. Therefore, in the present study the investigators wish to investigate the effect of concentration/meditation on autonomic nervous system activity and the inflammatory response during experimental human endotoxemia in a controlled manner, by comparing a group of subjects that are trained by the iceman and practice the concentration/meditation technique with a group of subjects which do not.

Official Title
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Concentration/Meditation as a Novel Means to Limit Inflammation: a Randomized Controlled Pilot Study

Conditions
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Autoimmune Diseases

Intervention / Treatment
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* Drug: Lipopolysaccharide
* Behavioral: Concentration/meditation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 and ≤35 yrs Male Healthy Travel insurance (for travel to Poland for the training in the concentration/meditation technique) Exclusion Criteria: Use of any medication Smoking Use of recreational drugs within 21 days prior to endotoxemia experiment day Use of caffeine or alcohol within 1 day prior to endotoxemia experiment day Previous participation in a trial where LPS was administered Surgery or trauma with significant blood loss or blood donation within 3 months prior to endotoxemia experiment day Participation in another clinical trial within 3 months prior to endotoxemia experiment day. History, signs, or symptoms of cardiovascular disease History of frequent vaso-vagal collapse or of orthostatic hypotension 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 Renal impairment: plasma creatinine >120 µmol/L Liver function abnormality: alkaline phosphatase>230 U/L and/or ALT>90 U/L History of asthma Obvious disease associated with immune deficiency. CRP > 20 mg/L, WBC > 12x109/L, or clinically significant acute illness, including infections, within 4 weeks before endotoxemia day

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Concentration/meditation group<br>Subjects in this arm will be performing the concentration/meditation technique of Wim Hof (The Iceman) prior to, during and after intravenously injected 2 ng/kg Lipopolysaccharide | Drug: Lipopolysaccharide<br>* LPS is used to elicit an inflammatory response in all subjects.<br>* Other names: Lipopolysaccharide (LPS) E. Coli 113:H 10:K negative;Behavioral: Concentration/meditation<br>* A self-taught concentration/meditation technique that Mr Wim Hof developed himself, characterized by cycles consisting of a few minutes of hyperventilation followed by breath holding for up to 1-2 minutes and deep concentration (mindset).<br>* Other names: Wim Hof Method;|
| Active Comparator: Control group<br>Subjects in this group will be intravenously injected with 2 ng/kg Lipopolysaccharide | Drug: Lipopolysaccharide<br>* LPS is used to elicit an inflammatory response in all subjects.<br>* Other names: Lipopolysaccharide (LPS) E. Coli 113:H 10:K negative;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentration of circulating TNF-α following LPS administration |  | 1 day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Circulating cytokines (including but not limited to IL-6, IL-10 and IL1RA), following LPS administration. |  | 1 day | 
| Body temperature after LPS administration |  | 1 day | 
| Hemodynamic parameters after LPS administration | Blood pressure, heart rate, saturation, respiratory rate. | 1 day | 
| Plasma cortisol levels after LPS administration |  | 1 day | 
| Plasma catecholamines levels after LPS administration |  | 1 day | 
| Heart Rate Variability following LPS administration |  | 1 day | 
| mtDNA concentrations following LPS administration |  | 1 day | 
| Transcriptome analysis of circulating leukocytes after LPS administration |  | 1 day | 
| Cytokine production by leukocytes ex vivo stimulated with LPS after LPS administration |  | 1 day | 
| Changes in cell surface markers and functionality of circulating neutrophils after LPS administration |  | 1 day | 
| effects of gut microbiome on inflammatory response elicited by LPS administration |  | 1 day | 
| Ethylene and NO concentrations in exhaled breath after LPS administration |  | 1 day | 
| Electrolyte concentrations in blood after concentration/meditation during endotoxemia |  | 1 day | 
| Cortisol concentration in scalp hair |  | 1 measurement 3 weeks after LPS administration | 
| Leukocyte counts and differentiation after LPS administration |  | 1 day | 
| Illness symptoms after LPS administration | shivering, headache, back ache, muscle ache, vomiting. | 1 day | 
| Blood viscosity after LPS administration |  | 1 day | 
| Platelet-leukocyte interactions after LPS administration | flow cytometric analysis of complexes between platelets on the one hand and monocytes, lymphocytes and neutrophils on the other hand. | 1 day | 
| beta-2 glycoprotein concentrations after LPS administration |  | 1 day | 
| cell surface markers on circulating leukocytes after LPS administration |  | 1 day | 
| Plasma endorphin levels after LPS administration |  | 1 day | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Endotoxemia, Autonomic Nervous System, Inflammation, Meditation, Concentration, Iceman, LPS, Cortisol, Catecholamines