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

November 26, 2010
June 6, 2011
March 2011
April 2011   (final data collection date for primary outcome measure)
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.
Same as current
Complete list of historical versions of study NCT01352871 on ClinicalTrials.gov Archive Site
  • 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

  • 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 acitivity [ 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

  • 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 ]

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

    Leucocyte count and differentiation will be measured

Not Provided
Not Provided
 
The Effects of Concentration/Meditation on the Innate Immune Response During Human Endotoxemia
The Effects of Concentration/Meditation on the Innate Immune Response During

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.
Not Provided
Observational
Observational Model: Case-Only
Time Perspective: Prospective
Not Provided
Not Provided
Non-Probability Sample

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

Innate Immune Response
  • 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
Concentration / meditation
The subject will try to influence the innate immune response by concentration / meditation in advance of and during endotoxemia
Interventions:
  • Behavioral: Concentration / meditation
  • Drug: lipopolysaccharide
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
1
May 2011
April 2011   (final data collection date for primary outcome measure)

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.
Male
45 Years to 55 Years
Yes
Contact information is only displayed when the study is recruiting subjects
Netherlands
 
NCT01352871
LPS-concentration
Yes
Professor P. Pickkers, Principle Investigator, Radboud University Nijmegen Medical Centre
Radboud University
Not Provided
Principal Investigator: Peter Pickkers, MD, PhD Radboud University
Radboud University
February 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP