The Effects of Concentration/Meditation on the Innate Immune Response During Human Endotoxemia

This study has been completed.
Sponsor:
Information provided by:
Radboud University
ClinicalTrials.gov Identifier:
NCT01352871
First received: November 26, 2010
Last updated: June 6, 2011
Last verified: February 2011
  Purpose

The innate immune response is the first line of defense against invading pathogens. Ideally, the inflammatory response is tightly regulated leading to both adequate protection to invading pathogens as well as limitation of an exuberant or unwanted immune response such as seen in sepsis or auto-immune diseases. It has become increasingly clear that the autonomic nervous system (ANS) and the innate immune response are intimately linked. Activation of the sympathetic division of ANS dampens inflammation via β2-adrenoceptors. On the other hand, in some cases, sympathetic drive can also stimulate the inflammatory response via α2-adrenoceptors. The parasympathetic branch of the ANS modulates the inflammatory response as well, since it was discovered that electrical stimulation of the efferent vagus nerve in rats greatly inhibits the innate immune response. Generally, the ANS is regarded as pure autonomic which can not be influenced by behavior. However, trough special concentration/mediation techniques mastered by certain individuals, it might be possible to modulate ANS activity. In addition, recent unpublished findings indicate that these concentration/meditation techniques can also influence the inflammatory response ex vivo.

In this study the investigators wish to investigate the effect of concentration/meditation on the innate immune response in vivo. In addition the investigators wish to elucidate the mechanism via which this effect is mediated. The investigators aim to use the so called human endotoxemia model. This model permits elucidation of key players in the immune response to a gram negative stimulus in vivo, therefore serving as a useful tool to investigate potential novel therapeutic strategies in a standardized setting.

Objectives:

Primary objective: The primary objective of the study is to determine the effect of concentration/meditation on the innate immune response induced by a lipopolysaccharide (LPS) challenge.

Secondary Objective(s):

  1. To determine the effects of concentration/meditation on ANS activity. Electroencephalography (EEG), heart-rate variability (HRV), muscle sympathetic nerve activity and plasma concentrations of catecholamines will be measured for this purpose.
  2. To determine if concentration/meditation can attenuate (subclinical) renal damage known to occur during human endotoxemia, markers of proximal and distal tubular damage will be measured at various time points.

Condition Intervention Phase
Innate Immune Response
Behavioral: Concentration / meditation
Drug: lipopolysaccharide
Phase 1

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Prospective
Official Title: The Effects of Concentration/Meditation on the Innate Immune Response During

Further study details as provided by Radboud University:

Primary Outcome Measures:
  • Change in Plasma TNF-alpha levels [ Time Frame: 0; 1; 1.5; 2; 3; 4; 6; 8; 12; 24 hrs after endotoxin administration ] [ Designated as safety issue: No ]
    Concentration of circulating TNF-alfa at certain timepoints.


Secondary Outcome Measures:
  • Change in plasma IL-6, IL-10 and IL-1ra levels and leukocyte counts [ Time Frame: 0; 1; 1.5; 2; 3; 4; 6; 8; 12; 24 hrs after endotoxin administration ] [ Designated as safety issue: No ]

    circulating IL-6, IL-10 and IL-1ra levels at certain timepoints.

    Leucocyte count and differentiation will be measured


  • Change in measures of autonomous nervous system activity [ Time Frame: at regulare intervals before and during endotoxemia ] [ Designated as safety issue: No ]
    • Electroencephalography (EEG)
    • Heart rate variability (HRV)
    • Plasma cathecholamines
    • Muscle sympathetic nerve activity (MSNA)

  • Change in markers of subclinical renal tubular damage [ Time Frame: before and at 0-3, 3-6, 6-9, 9-12 and 12-24 hrs after endotoxemia ] [ Designated as safety issue: No ]

    determination of markers in urine collected within the above mentioned intervals.

    GSTA1-1 will be used as marker for proximal tubular damage GSTP1-1 will be used as marker for distal tubular damage



Estimated Enrollment: 1
Study Start Date: March 2011
Study Completion Date: May 2011
Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Concentration / meditation
The subject will try to influence the innate immune response by concentration / meditation in advance of and during endotoxemia
Behavioral: Concentration / meditation
from 30 minutes before endotoxin administration to 1,5 hrs after endotoxin administration the subject is concentrating / meditating with the goal to influence the innate immune response
Drug: lipopolysaccharide
lipopolysaccharide 2ng/kg intravenously
Other Names:
  • LPS
  • endotoxin

  Eligibility

Ages Eligible for Study:   45 Years to 55 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

One healthy male volunteer that masters the concentration/meditation technique.

Criteria

Inclusion Criteria:

  • 45 - 55 years of age
  • male
  • Healthy

Exclusion Criteria:

  • Use of any medication.
  • Smoking.
  • Bleeding disorder.
  • Previous spontaneous vagal collapse.
  • History, signs or symptoms of cardiovascular disease.
  • Cardiac conduction abnormalities on the ECG consisting of a 2nd degree atrioventricular block or a complex bundle branch block.
  • Hypertension (defined as RR systolic > 160 or RR diastolic > 90).
  • Hypotension (defined as RR systolic < 100 or RR diastolic < 50).
  • Renal impairment (defined as plasma creatinin >120 μmol/l).
  • Liver enzyme abnormalities or positive hepatitis serology.
  • Positive HIV serology or any other obvious disease associated with immune deficiency.
  • Febrile illness in the week before the LPS challenge.
  • Participation in another drug trial or donation of blood 3 months prior to the planned LPS challenge.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01352871

Locations
Netherlands
Radboud University Nijmegen Medical Centre
Nijmegen, Gelderland, Netherlands, 6511HB
Sponsors and Collaborators
Radboud University
Investigators
Principal Investigator: Peter Pickkers, MD, PhD Radboud University
  More Information

No publications provided

Responsible Party: Professor P. Pickkers, Principle Investigator, Radboud University Nijmegen Medical Centre
ClinicalTrials.gov Identifier: NCT01352871     History of Changes
Other Study ID Numbers: LPS-concentration
Study First Received: November 26, 2010
Last Updated: June 6, 2011
Health Authority: Netherlands: Medical Ethics Review Committee (METC)
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Radboud University:
Immunity, Innate
Attention
Concentration

ClinicalTrials.gov processed this record on July 24, 2014