Inflammation; SkinNCT03779360
Intradermal LPS and Antibiotics
A study testing Erythromycin 4% topical gel formulation:, Clindamycin 1% lotion formulation: and Prednisolone tablet (0.5mg/kg; parallel comparison): in people with Inflammation; Skin, run by Centre for Human Drug Research, Netherlands at 1 site in Netherlands.
Trial summary
Erythromycin and clindamycin are believed to have anti-inflammatory aspects. This study investigates the possible anti-inflammatory effects of erythromycin and clindamycin. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Inflammation; Skin
- What is being tested?
- Erythromycin 4% topical gel formulation:, Clindamycin 1% lotion formulation: and Prednisolone tablet (0.5mg/kg; parallel comparison):
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 1 siteNetherlands
- Study dates
- 12 Oct 2018to 23 Feb 2019
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy male or female 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;
- Body mass index (BMI) between 18 and 30 kg/m2, inclusive, and with a minimum weight of 50 kg;
- Fitzpatrick skin type I-III (Caucasian);
- Able and willing to give written informed consent and to comply with the study restrictions.
- Able to work with the eDiary app.
Who cannot join
- Any disease associated with immune system impairment, including auto-immune diseases, HIV and transplantation patients;
- Type 1 or type 2 diabetes mellitus;
- Any vaccination within the last 3 months;
- Family history of psoriasis;
- History of pathological scar formation (keloid, hypertrophic scar);
- Have any current and / or recurrent pathologically, clinical significant skin condition at the treatment area (i.e. atopic dermatitis);
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- Hypersensitivity for dermatological marker at screening;
- Requirement of immunosuppressive or immunomodulatory medication within 30 days prior to enrollment or planned to use during the course of the study;
- Excessive sun exposure or a tanning booth within 3 weeks of enrollment;
- Participation in an investigational drug or device study within 3 months prior to screening or more than 4 times a year;
- 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;
- Current smoker and/or regular user of other nicotine-containing products (e.g., patches);
- History of or current drug or substance abuse considered significant by the PI (or medically qualified designee), including a positive urine drug screen.
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Centre for Human Drug Research
Leiden, South Holland, 2333 CL
About this study
Official title: Investigating Anti-inflammatory Effects of Topical Antibiotics in an LPS Skin Challenge Model
Erythromycin and clindamycin are believed to have anti-inflammatory aspects. This study investigates the possible anti-inflammatory effects of erythromycin and clindamycin.
Read the detailed description
Convincing mechanistic reports on the immunomodulatory action of erythromycin and clindamycin are scarce, rarely based on experiments in freshly isolated human immune cells, and potentially contradicting. Moreover, direct immunomodulatory effects of both antibiotics have never been demonstrated in vivo. The Centre for Human Drug Research Biomarker lab has studied in depth the immunomodulatory actions of erythromycin and clindamycin in vitro. These in vitro experiments on primary human immune cells demonstrated that both erythromycin and clindamycin are able to modulate the immune response of peripheral blood mononuclear cells upon stimulation with different immune triggers such as lipopolysaccharide (LPS) and polyI:C. In this current study the in vitro work will be translated to an in vivo study where it will be made into an intradermal LPS skin challenge model in healthy volunteers.
- Conditions
- Inflammation; Skin
- Being tested
- Erythromycin 4% topical gel formulation:, Clindamycin 1% lotion formulation:, Prednisolone tablet (0.5mg/kg; parallel comparison):, Clobetasol propionate 0.05% topical formulation (crossover comparison):, Lipopolysaccharide
- Medical subject headings
- Dermatitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Erythromycin 4% topical gel formulation:Drug
7 day pre-treatment with erythromycin and clindamycin applied twice daily on marked area on left (erythromycin) and right side (clindamycin) of the volar lower arm. Erythromycin is a bacteriostatic antibiotic that belongs to the macrolide group of antibiotics. Macrolides act as bacteriostatic by reversibly binding to the P site on the 50S subunit of bacterial ribosomes. A topical gel formulation with hyprolose and ethanol.
Clindamycin 1% lotion formulation:Drug
7 day pre-treatment with erythromycin and clindamycin applied twice daily on marked area on left (erythromycin) and right side (clindamycin) of the volar lower arm. Clindamcin is a bacteriostatic antibiotic that belongs to the lincosamide group of antibiotics. Lincosamides act as bacteriostatic by reversibly binding to the P site on the 50S subunit of bacterial ribosomes. A topical lotion formulation with ethanol.
Prednisolone tablet (0.5mg/kg; parallel comparison):Drug
2 day pre-treatment with prednisolone daily dose 0.5mg/kg (0.25mg/kg in the morning and 0.25mg/kg in the evening). Prednisolone tablet (0.5mg/kg; parallel comparison): Prednisolone is a synthetic corticosteroid with predominant glucocorticoid activity and as such it is widely used in the treatment for inflammatory and autoimmune diseases. Prednisolone exerts its effect by binding to cytoplasmic glucocorticoid receptors and subsequently activates glucocorticoid receptor mediated gene expression. This results in synthesis of certain anti-inflammatory proteins, while inhibiting the synthesis of certain inflammatory mediators.
Clobetasol propionate 0.05% topical formulation (crossover comparison):Drug
2 day pre-treatment with clobetasol propionate 0.05% topical formulation applied twice daily on marked area on left or right side of the volar lower arm.
Clobetasol propionate 0.05% topical formulation (crossover comparison):
Clobetasol propionate is a potent synthetic corticosteroid with anti-inflammatory, anti-pruritic, and vasoconstrictive properties. Clobetasol propionate exerts its effect by binding to cytoplasmic glucocorticoid receptors and subsequently activates glucocorticoid receptor mediated gene expression. This results in synthesis of certain anti-inflammatory proteins, while inhibiting the synthesis of certain inflammatory mediators. Specifically, clobetasol propionate appears to induce phospholipase A2 inhibitory proteins, thereby controlling the release of the inflammatory precursor arachidonic acid from membrane phospholipids by phospholipase A2.
LipopolysaccharideOther
Also called LPS
As TLR4 agonist, 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 the National Institute of Health (NIH). Subjects will receive two intradermal doses of LPS in each forearm on day 0 (4 LPS injections in total, except for subjects 1-6 who receive none and subjects 25-27 will receive 2 LPS injections, only in the right arm). The dose per injection is 10 ng.
| Study group | Role | What they receive |
|---|---|---|
| Subjects 1-6 | Active comparator | 7 day treatment of erythromycin and clindamycin twice daily on indicated skin areas prior to Clobetasol treatment; randomized either on the left or right arm for 2 days. Receives: Drug: Erythromycin 4% topical gel formulation:; Drug: Clindamycin 1% lotion formulation:; Drug: Clobetasol propionate 0.05% topical formulation (crossover comparison): |
| Subjects 7-24 | Experimental | 7 day treatment of erythromycin and clindamycin twice daily on indicated skin area prior to 4 Lipopolysaccharide injections and Clobetasol treatment; randomized either on the left or right arm for 2 days. Receives: Drug: Erythromycin 4% topical gel formulation:; Drug: Clobetasol propionate 0.05% topical formulation (crossover comparison):; Other: Lipopolysaccharide |
| Subjects 25-30 | Active comparator | 0.5mg/kg prednisolone two days prior to Lipopolysaccharide injections Receives: Drug: Prednisolone tablet (0.5mg/kg; parallel comparison):; Other: Lipopolysaccharide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in perfusion by Laser speckle contrast imaging (LSCI)
Cutaneous microcirculation between pre and post-dose will be assessed using the laser speckle imager.
Measured: Baseline, 3, 6, 10, 24 and 48 hours post LPS injection
Change in erythema by Antera 3D camera and 2D camera
Standardized photographs will be taken using the Antera camera (Antera 3D, Miravex, Ireland).
Measured: Baseline, 3, 6, 10, 24 and 48 hours post LPS injection
Change in erythema by clinical evaluation (erythema grading scale)
At the specific time points pre and post dose the colour of the injected area is scored (erythema index), on a 4 point scale; normal, mild, moderate, severe.
Measured: Baseline, 3, 6, 10, 24 and 48 hours post LPS injection
Change in temperature by thermography in celsius
Skin temperature will be measured using a thermal imaging camera.
Measured: Baseline, 3, 6, 10, 24 and 48 hours post LPS injection
Change in skin microbiome
Collection of skin culture samples is a non-invasive procedure where a sterile polyester flock tip per site is passed along the surface of treated and non-treated areas.
bacteria studied include but are not limited to: Acinetobacter Anaerococcus Corynebacterium Enhydrobacter Finegoldia Lactobacillus Micrococcus Paracoccus Peptoniphilus Prevotella Propionibacterium Staphylococcus Streptococcus
Measured: Baseline, 3, 6, 10, 24 and 48 hours post LPS injection
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Dec 2018
- Study start12 Oct 2018
- Primary completion23 Feb 2019
- Study completion23 Feb 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Inflammation; SkinStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Factorial
- Model description
- An interventional, open-label, comparator controlled study to investigate the immunomodulatory effects of erythromycin and clindamycin in an LPS skin challenge model in healthy volunteers.
- Masking
- None (open label)
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centre for Human Drug Research, Netherlands
- Sponsor type
- University, hospital or other
- Collaborators
- Maruho Co., Ltd.
- Responsible party
- Sponsor
- Investigators
- Matthijs Moerland, PhD, Principal investigator, Researc Director
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03779360
- Sponsor's protocol ID
- CHDR1752-B
- Status last verified
- Aug 2021
- First submitted
- 10 Dec 2018
- Last updated
- 3 Aug 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigating Anti-inflammatory Effects of Topical Antibiotics in an LPS Skin Challenge Model
- ClinicalTrials.gov ID
- NCT03779360
- Acronym / sponsor ID
- CHDR1752-B
- Conditions
- Inflammation; Skin
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Centre for Human Drug Research, NetherlandsUniversity, hospital or other
- Collaborators
- Maruho Co., Ltd.
- Study start
- 12 Oct 2018 (actual)
- Primary completion
- 23 Feb 2019 (actual)
- Study completion
- 23 Feb 2019 (actual)
- First posted
- 19 Dec 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Erythromycin and clindamycin are believed to have anti-inflammatory aspects. This study investigates the possible anti-inflammatory effects of erythromycin and clindamycin.
Detailed description
Convincing mechanistic reports on the immunomodulatory action of erythromycin and clindamycin are scarce, rarely based on experiments in freshly isolated human immune cells, and potentially contradicting. Moreover, direct immunomodulatory effects of both antibiotics have never been demonstrated in vivo. The Centre for Human Drug Research Biomarker lab has studied in depth the immunomodulatory actions of erythromycin and clindamycin in vitro. These in vitro experiments on primary human immune cells demonstrated that both erythromycin and clindamycin are able to modulate the immune response of peripheral blood mononuclear cells upon stimulation with different immune triggers such as lipopolysaccharide (LPS) and polyI:C. In this current study the in vitro work will be translated to an in vivo study where it will be made into an intradermal LPS skin challenge model in healthy volunteers.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- An interventional, open-label, comparator controlled study to investigate the immunomodulatory effects of erythromycin and clindamycin in an LPS skin challenge model in healthy volunteers.
| Arm | Type | Receives |
|---|---|---|
| Subjects 1-6 | Active comparator | Drug: Erythromycin 4% topical gel formulation:, Drug: Clindamycin 1% lotion formulation:, Drug: Clobetasol propionate 0.05% topical formulation (crossover comparison):7 day treatment of erythromycin and clindamycin twice daily on indicated skin areas prior to Clobetasol treatment; randomized either on the left or right arm for 2 days. |
| Subjects 7-24 | Experimental | Drug: Erythromycin 4% topical gel formulation:, Drug: Clobetasol propionate 0.05% topical formulation (crossover comparison):, Other: Lipopolysaccharide7 day treatment of erythromycin and clindamycin twice daily on indicated skin area prior to 4 Lipopolysaccharide injections and Clobetasol treatment; randomized either on the left or right arm for 2 days. |
| Subjects 25-30 | Active comparator | Drug: Prednisolone tablet (0.5mg/kg; parallel comparison):, Other: Lipopolysaccharide0.5mg/kg prednisolone two days prior to Lipopolysaccharide injections |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Healthy male or female 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;
- Body mass index (BMI) between 18 and 30 kg/m2, inclusive, and with a minimum weight of 50 kg;
- Fitzpatrick skin type I-III (Caucasian);
- Able and willing to give written informed consent and to comply with the study restrictions.
- Able to work with the eDiary app.
Key exclusion criteria (13 listed)
- Any disease associated with immune system impairment, including auto-immune diseases, HIV and transplantation patients;
- Type 1 or type 2 diabetes mellitus;
- Any vaccination within the last 3 months;
- Family history of psoriasis;
- History of pathological scar formation (keloid, hypertrophic scar);
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Erythromycin 4% topical gel formulation:7 day pre-treatment with erythromycin and clindamycin applied twice daily on marked area on left (erythromycin) and right side (clindamycin) of the volar lower arm. Erythromycin is a bacteriostatic antibiotic that belongs to the macrolide group of antibiotics. Macrolides act as bacteriostatic by reversibly binding to the P site on the 50S subunit of bacterial ribosomes. A topical gel formulation with hyprolose and ethanol. | Drug | Subjects 1-6, Subjects 7-24 |
| Clindamycin 1% lotion formulation:7 day pre-treatment with erythromycin and clindamycin applied twice daily on marked area on left (erythromycin) and right side (clindamycin) of the volar lower arm. Clindamcin is a bacteriostatic antibiotic that belongs to the lincosamide group of antibiotics. Lincosamides act as bacteriostatic by reversibly binding to the P site on the 50S subunit of bacterial ribosomes. A topical lotion formulation with ethanol. | Drug | Subjects 1-6 |
| Prednisolone tablet (0.5mg/kg; parallel comparison):2 day pre-treatment with prednisolone daily dose 0.5mg/kg (0.25mg/kg in the morning and 0.25mg/kg in the evening). Prednisolone tablet (0.5mg/kg; parallel comparison): Prednisolone is a synthetic corticosteroid with predominant glucocorticoid activity and as such it is widely used in the treatment for inflammatory and autoimmune diseases. Prednisolone exerts its effect by binding to cytoplasmic glucocorticoid receptors and subsequently activates glucocorticoid receptor mediated gene expression. This results in synthesis of certain anti-inflammatory proteins, while inhibiting the synthesis of certain inflammatory mediators. | Drug | Subjects 25-30 |
| Clobetasol propionate 0.05% topical formulation (crossover comparison):2 day pre-treatment with clobetasol propionate 0.05% topical formulation applied twice daily on marked area on left or right side of the volar lower arm. Clobetasol propionate 0.05% topical formulation (crossover comparison): Clobetasol propionate is a potent synthetic corticosteroid with anti-inflammatory, anti-pruritic, and vasoconstrictive properties. Clobetasol propionate exerts its effect by binding to cytoplasmic glucocorticoid receptors and subsequently activates glucocorticoid receptor mediated gene expression. This results in synthesis of certain anti-inflammatory proteins, while inhibiting the synthesis of certain inflammatory mediators. Specifically, clobetasol propionate appears to induce phospholipase A2 inhibitory proteins, thereby controlling the release of the inflammatory precursor arachidonic acid from membrane phospholipids by phospholipase A2. | Drug | Subjects 1-6, Subjects 7-24 |
| LipopolysaccharideAlso: LPSAs TLR4 agonist, 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 the National Institute of Health (NIH). Subjects will receive two intradermal doses of LPS in each forearm on day 0 (4 LPS injections in total, except for subjects 1-6 who receive none and subjects 25-27 will receive 2 LPS injections, only in the right arm). The dose per injection is 10 ng. | Other | Subjects 25-30, Subjects 7-24 |
Primary outcome
Change in perfusion by Laser speckle contrast imaging (LSCI)
Time frame: Baseline, 3, 6, 10, 24 and 48 hours post LPS injection
Cutaneous microcirculation between pre and post-dose will be assessed using the laser speckle imager.
Change in erythema by Antera 3D camera and 2D camera
Time frame: Baseline, 3, 6, 10, 24 and 48 hours post LPS injection
Standardized photographs will be taken using the Antera camera (Antera 3D, Miravex, Ireland).
Change in erythema by clinical evaluation (erythema grading scale)
Time frame: Baseline, 3, 6, 10, 24 and 48 hours post LPS injection
At the specific time points pre and post dose the colour of the injected area is scored (erythema index), on a 4 point scale; normal, mild, moderate, severe.
Change in temperature by thermography in celsius
Time frame: Baseline, 3, 6, 10, 24 and 48 hours post LPS injection
Skin temperature will be measured using a thermal imaging camera.
Change in skin microbiome
Time frame: Baseline, 3, 6, 10, 24 and 48 hours post LPS injection
Collection of skin culture samples is a non-invasive procedure where a sterile polyester flock tip per site is passed along the surface of treated and non-treated areas. bacteria studied include but are not limited to: Acinetobacter Anaerococcus Corynebacterium Enhydrobacter Finegoldia Lactobacillus Micrococcus Paracoccus Peptoniphilus Prevotella Propionibacterium Staphylococcus Streptococcus
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Aug 2021.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Matthijs Moerland, PhD principal investigator
Researc Director
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Erythromycin 4% topical gel formulation:, Clindamycin 1% lotion formulation: and Prednisolone tablet (0.5mg/kg; parallel comparison): in people with Inflammation; Skin, run by Centre for Human Drug Research, Netherlands at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in perfusion by Laser speckle contrast imaging (LSCI) (time frame: Baseline, 3, 6, 10, 24 and 48 hours post LPS injection). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Aug 2021; AzTrials last refreshed its copy on 28 Oct 2026.