Condition category
Not Applicable
Date applied
23/10/2020
Date assigned
16/11/2020
Last edited
13/11/2020
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting
Publication status
Results overdue

Plain English Summary

Background and study aims
Inflammation is a process by which your body's white blood cells and the things they make protect you from infection from outside invaders, such as bacteria and viruses.
New anti-inflammatory drugs are hard to evaluate in healthy volunteers, as healthy volunteers do not have ongoing inflammation. We want to induce a local inflammatory reaction in healthy volunteers and study this reaction so that the induced inflammatory reaction can be used in future clinical trials with new anti-inflammatory drugs.

Who can participate?
Healthy non-smoking male volunteers age 18 - 45

What does the study involve?
The study involves the administration of LPS (purified lipopolysaccharide) which is part of a bacteria. The administration is done with a needle into the skin of the forearms. Subjects also receive an injection with a salt solution which acts as placebo. The response to the LPS and salt solution are monitored for 48 hours. In order to study the response, suction blisters are raised and skin punch biopsies are taken, next to that several cameras will be used that can measure heat, redness and blood flow in the skin.

What are the possible benefits and risks of participating?
There are no benefits for the volunteers. Risks include a small scar from the biopsy and a pigmentated spot on the skin from the suction blister.

Where is the study run from?
Centre for Human Drug Research, Leiden (The Netherlands)

When is the study starting and how long is it expected to run for?
September 2017 to November 2018

Who is funding the study?
1. Centre for Human Drug Research (The Netherlands)
2. Cutanea Life Sciences (The Netherlands)

Who is the main contact?
Matthijs Moerland, mmoerland@chdr.nl

Trial website

Contact information

Type

Public

Primary contact

Dr Matthijs Moerland

ORCID ID

Contact details

Centre for Human Drug Research
Zernikedreef 8
Leiden
2333 CL
Netherlands
+31 (0)71 524 6400
mmoerland@chdr.nl

Type

Scientific

Additional contact

Dr Matthijs Moerland

ORCID ID

Contact details

Centre for Human Drug Research
Zernikedreef 8
Leiden
2333 CL
Netherlands
+31 (0)71 524 6400
mmoerland@chdr.nl

Additional identifiers

EudraCT number

Nil known

ClinicalTrials.gov number

Nil known

Protocol/serial number

CHDR1752

Study information

Scientific title

Development of a dermal TLR4 challenge in healthy volunteers

Acronym

Study hypothesis

The aim of this study is to characterize the inflammatory response upon intradermal LPS injection in healthy volunteers. By doing so we create a challenge model that temporarily induces skin inflammation via a specific pathway which enables future application as proof-of-pharmacology or drug profiling in drug developmental programs.

Ethics approval

Approved 16/05/2018, Stichting Beoordeling Ethiek Biomedisch Onderzoek (Dr. Nassaulaan 10, 9401HK Assen, Netherlands; +31 (0)592 405871; info@stbebo.nl), ref: NL65297.056.18

Study design

Interventional non-randomized controlled trial

Primary study design

Interventional

Secondary study design

Non randomised study

Trial setting

Other

Trial type

Other

Patient information sheet

Not available in web format, please use contact details to request a participant information sheet

Condition

The aim of this study is to characterize the inflammatory response upon intradermal LPS injection in healthy volunteers

Intervention

LPS, purified lipopolysaccharide prepared from Escherichia Coli: 113: H10:K negative (U.S. Standard
Reference Endotoxin) will be used. This LPS batch is manufactured in the US by List Biological Laboratories. Subjects will receive in total two or four intradermal doses of LPS on the lower forearms on day 0 . The dose per injection is 10 ng. An intradermal saline (NaCl 0.9%) injection will act as placebo.

Subjects 1 – 6 received one saline injection and two LPS injections, subjects 7 – 18 received one saline injection and four LPS injections.

Intervention type

Other

Phase

Drug names

Primary outcome measure

1. Non-invasive measures:
1.1. Skin Perfusion was measured by Laser speckle contrast imaging (LSCI) pre LPS/saline administration and at 3h 6h, 10h, 24h and 48h after administration
1.2. Erythema was measured by Antera 3D camera pre LPS/saline administration and at 3h 6h, 10h, 24h and 48h after administration
1.3. Erythema was scored by a physician (erythema grading scale) pre LPS/saline administration and at 3h 6h, 10h, 24h and 48h after administration
1.4. Temperature was measured by thermography pre LPS/saline administration and at 3h 6h, 10h, 24h and 48h after administration
2. Invasive measures:
Skin punch biopsies were taken pre LPS/saline administration and at 3h 6h, 10h, 24h and 48h after administration and analyzed for the following:
2.1. Immunochemistry: Neutrophils, Monocytes/macrophages, CD4+ lymphocytes, CD8+ lymphocytes, CD1a+ dendritic cells
CD19+ B cells
2.2. mRNA analysis by qPCR: IFN-gamma, IL10, IL1-beta, IL6, IL8, TNF, MXA
3. Suction blisters were raised pre LPS/saline administration and at 3h 6h, 10h, 24h and 48h after administration and analyzed for the following:
3.1. Flowcytometry: Neutrophils, classical monocytes, non-classical monocytes, intermediate monocytes, dendritic cells, NK cells, CD4 T cells, CD8 T cells, B cells.
MSD (protein): IFN-gamma, IL10, IL1-beta, IL6, IL8, TNF

Secondary outcome measures

1. Adverse events were monitored throughout the study
2. Blood pressure, heart rate and temperature were measured pre LPS/saline administration and at 3h 6h, 10h, 24h and 48h after administration
3. Local tolerance was measured pre LPS/saline administration and at 3h 6h, 10h, 24h and 48h after administration by using Numeric Rating Scale (NRS) for pruritus and pain for the injection site
4. Circulating cytokines and leukocytes were measured pre LPS/saline administration and at 3h 6h, 10h, 24h and 48h after administration

Overall trial start date

27/09/2017

Overall trial end date

12/11/2018

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Healthy male subjects, 18 to 45 years of age, inclusive. Healthy status is defined by absence of evidence of any active or chronic disease following a detailed medical and surgical history, a complete physical examination including vital signs, 12-lead ECG, hematology, blood chemistry, blood serology and urinalysis
2. Body mass index (BMI) between 18 and 30 kg/m², inclusive, and with a minimum weight of 50 kg
3. Fitzpatrick skin type I-III (Caucasian)
4. Able and willing to give written informed consent and to comply with the study restrictions

Participant type

Healthy volunteer

Age group

Adult

Gender

Male

Target number of participants

18

Total final enrolment

18

Participant exclusion criteria

1. Any disease associated with immune system impairment, including auto-immune diseases, HIV and transplantation patients
2. Any vaccination within the last 3 months
3. Family history of psoriasis
4. History of pathological scar formation (keloid, hypertrophic scar)
5. Have any current and / or recurrent pathologically, clinical significant skin condition at the treatment area (i.e. atopic dermatitis)
6. Hypersensitivity for dermatological marker at screening
7. Requirement of immunosuppressive or immunomodulatory medication within 30 days prior to enrollment or planned to use during the course of the study
8. Tanning due to sunbathing, excessive sun exposure or a tanning booth within 3 weeks of enrollment
9. Participation in an investigational drug or device study within 3 months prior to screening or more than 4 times a year
10. Loss or donation of blood over 500 mL within three months prior to screening. Or the donation of plasma within 14 days prior to screening
11. Current smoker and/or regular user of other nicotine-containing products (e.g., patches)
12. History of or current drug or substance abuse considered significant by the PI (or medically qualified designee), including a positive urine drug screen

Recruitment start date

17/05/2018

Recruitment end date

04/09/2018

Locations

Countries of recruitment

Netherlands

Trial participating centre

Centre for Human Drug Research
Zernikedreef 8
Leiden
2333 CL
Netherlands

Sponsor information

Organisation

Centre for Human Drug Research

Sponsor details

Zernikedreef 8
Leiden
2333 CL
Netherlands
+31 (0)71 524 6400
clintrials@chdr.nl

Sponsor type

Research organisation

Website

http://www.chdr.nl/

Funders

Funder type

Industry

Funder name

Cutanea Life Sciences

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Planned publication in a high-impact peer-reviewed journal.

IPD sharing statement:
All data generated or analysed during this study will be included in the subsequent results publication.

Intention to publish date

01/02/2021

Participant level data

Other

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

13/11/2020: Trial’s existence confirmed by Stichting Beoordeling Ethiek Biomedisch Onderzoek.