Individual Differences in Acute Response to Experimental Inflammation: Microcirculatory Changes and Psychological Predictors

NCT06618716 | Enrolling By Invitation

• 1 other identifier: 2023-07974-01
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

The physiological and behavioral responses to inflammatory vary greatly between individuals. The knowlegde about what causes these differences is sparse but plausible explanations are variations in sensitivity to peripheral inflammation. The goal of the study is to understand microcirculatory changes in skin and their possible correlation with conventional measurements of sickness and disease in humans. A better understanding of possible psychological predictors of sickness behaviour is also warranted as it may affect the results. The general aim of the study is to assess microcirculatory changes in skin of the face, chest, hands and feet using different optical imaging techniques, and to identify psychological predictors in the acute behavioral response to experimentally induced inflammation. The participants are healthy volunteers in the age of 18-40 years of both sex/genders. The main questions to answer are:

• Fill in psychometric questionnaires
• Be measured with bio-optical imaging methods at regular intervalls.
• Be monitored with regular medical parameters such as blood pressure, oxygen saturation, puls etc When the volunteers feel recovered and the medical staff are confident of the recovery the volunteers will be discharged.

Conditions

Inflammation Biomarkers; Inflammation

Keywords

Microcirculatory status; Sickness behaviour; Lipopolysaccharide; Non-invasive monitoring

Outcome Measures

Primary Outcomes (12)

• How does inflammation affect the behavioral response?

  Behavioral response in psychometric tests measuring sickness behavior, negative mood, anxiety and fatigue on Likert scales.

  Baseline

• How does inflammation affect the behavioral response?

  Behavioral response in psychometric tests measuring sickness behavior, negative mood, anxiety and fatigue on Likert scales.

  during the intervention

• How does inflammation affect the behavioral response?

  Behavioral response in psychometric tests measuring sickness behavior, negative mood, anxiety and fatigue on Likert scales.

  after the intervention

• Microcirculatory changes in skin measured with bio-optical instruments

  \- Red Blood Cell tissue fraction - %

  Baseline

• Microcirculatory changes in skin measured with bio-optical instruments

  \- Red Blood Cell tissue fraction - %

  during the intervention

• Microcirculatory changes in skin measured with bio-optical instruments

  \- Red Blood Cell tissue fraction - %

  after the intervention

• Microcirculatory changes in skin measured with bio-optical instruments

  \- Blood flow - mm/s

  Baseline

• Microcirculatory changes in skin measured with bio-optical instruments

  Blood flow - mm/s

  during the intervention

• Microcirculatory changes in skin measured with bio-optical instruments

  \- Blood flow - mm/s

  after the intervention

• Changes in skin and core temperature

  Measured in degrees Celsius

  Baseline

• Changes in skin and core temperature

  Measured in degrees Celsius

  during the intervention

• Changes in skin and core temperature

  Measured in degrees Celsius

  after the intervention

Study Arms (2)

Endotoxin

ACTIVE COMPARATOR

The USP (United States Pharmacopeia Convention) Endotoxin RS (LPS; Endotoxin Reference Standard, Escherichia coli, Pharmacopeia, Rockville, MD, US) will be ordered.and comes as a lyophilized (freeze-dried) powder, and each vial contains 10,000 USP Endotoxin Units. Each vial contains approximately 1 microgram of Endotoxin. The lyophilized LPS will be dissolved in 5mL sterile water to obtain a solution at 200 ng/mL. This solution will be aliquoted in 400μL (thus containing 80ng endotoxin) and stored at -20°C. Aliquots will be sent for microbial safety testing routine and verification of endotoxin concentration to a certified laboratory. On the study day, 2100μL of physiological saline (sterile, pyrogen-free isotonic NaCl solution) will be added to the aliquot to obtain a final concentration of 32 ng/mL. The amount of solution to inject will then be calculated according to the participant's weight \[in mL = (0.8 x weight) / 32\].

Biological: endotoxin escherichia coli (E. coli) lipopolysaccharide (LPS)

Placebo

PLACEBO COMPARATOR

An equivolume of sterile physiological saline (NaCl 0.9%) will be used as placebo.

Other: Placcebo

Interventions

endotoxin escherichia coli (E. coli) lipopolysaccharide (LPS) BIOLOGICAL

Intravenous administration of endotoxin (0.8 ng/kg body weight)

Endotoxin

Placcebo OTHER

Placebo injection of 0.9% NaCl

Placebo

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy
• years-old
• Consent form signed
• Having a Swedish personal identification number (personnummer)

You may not qualify if:

• Non-fluent in Swedish
• Unable to read
• Unable or unwilling to provide informed consent
• BMI below 18.5 or above 25 kg/m2
• Smoking
• Excessive alcohol consumption
• Pregnancy or breastfeeding
• Positive on drug screening
• Current somatic disease including skin disease affecting the measurement areas
• Current depression, anxiety, sleep disturbances or other psychiatric illnesses
• Abnormal blood analyses: abnormal clinical levels in blood cell counts, hemoglobin, sodium, potassium, chloride, calcium, phosphate, creatinine, blood urea nitrogen, uric acid, glucose, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transpeptidase, bilirubin, thromboplastin time and partial thromboplastin time
• High-sensitivity C-reactive protein \> 10 mg/L.
• History of cardiovascular, pneumological, immune disease
• Moderate viral or bacterial infection in the past two weeks
• Severe and/or long-term COVID-19: positive SARS-CoV-2 PCR-test or antigen-test and/or history of symptoms since February 2020 indicative of infection with SARS-CoV-2 (fever, cough, sore throat, runny or blocked nose, nausea, muscle pain, shortness of breath), which was of high intensity and/or of long duration (≥ 8 weeks).

Sponsors & Collaborators

• University Hospital, Linkoeping: lead
• Karolinska Institutet: collaborator
• Stockholm University: collaborator

Study Sites (1)

Department of emergency medicine, Linköping University Hospital, Region Östergötland

Linköping, Sweden

Location

MeSH Terms

Conditions

Inflammation

Interventions

endotoxin, Escherichia coli; Lipopolysaccharides

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Glycoconjugates; Carbohydrates; Polysaccharides, Bacterial; Polysaccharides; Lipids; Antigens, Bacterial; Antigens; Biological Factors; Endotoxins; Bacterial Toxins; Toxins, Biological

Study Officials

• Rani Toll, PhD

  Department of Emergency Medicine in Linköping, and Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: September 12, 2024
• First Posted: October 1, 2024
• Study Start: September 5, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2029
• Last Updated: October 1, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, CSR
• Time Frame: 17/9/24 to 31/12/29
• Access Criteria: The co-investigators from Karolinska Institutet Stockholm University will be able to access IPD and supporting information.

Locations

SE (1)