To assess the immunomodulatory effects of erythromycin and clindamycin in healthy volunteers.
ID
Source
Brief title
Condition
- Epidermal and dermal conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Tolerability / safety endpoints
*Monitoring Adverse events (AEs)
* Monitoring BP, HR and T
*Local tolerance (Numeric Rating Scale (NRS) pruritus and pain)
*Circulating cytokines (TNF*, IL-6, IL-8, IL-1*), and leukocytes
Pharmacodynamic endpoints
Non-invasive measures:
*Perfusion by Laser speckle contrast imaging (LSCI)
*Erythema by Antera 3D camera / 2D camera
*Erythema by clinical evaluation (erythema grading scale)
*Temperature by thermography
*Skin microbiome
Invasive measures:
Suction blister exudates:
o Cytokines and chemokines (protein, TBD)
o Flow cytometry:
*Neutrophils
*Monocytes/macrophages
*CD4+ lymphocytes
*CD8+ lymphocytes
*CD56+ lymphocytes
*CD1c dendritic cells
Secondary outcome
NA
Background summary
Convincing mechanistic reports on the immunomodulatory action of erythromyxin
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 CHDR 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 PBMCs
upon stimulation with different immune triggers such as lipopolysaccharide
(LPS) and polyI:C. In this current study we will translate the in vitro work to
an in vivo study where we make use an intradermal LPS skin challenge model in
healthy volunteers.
Study objective
To assess the immunomodulatory effects of erythromycin and clindamycin in
healthy volunteers.
Study design
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.
Study burden and risks
Treatment with topical erythromycin, clindamycin is known to be safe and well
tolerated. Both clobetasol propionate and prednisone are known for their side
effects when used in a high dose for a longer period, however in this study
both products are only used for a limited amount of days (up to 4 days) and
therefore no lasting effects are likely to occur. Most flu like symptoms due to
the LPS are dose-related and resolved within 2-6 hours. Complications of the
blister include infection (rare) and post inflammatory hyperpigmentation. To
minimize the risk of post inflammatory hyperpigmentation Fitzpatrick skin types
4-6 are excluded and only healthy males are included in this study.
Zernikedreef 8
Leiden 2333CL
NL
Zernikedreef 8
Leiden 2333CL
NL
Listed location countries
Age
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.
5. Able to work with the eDiary app.
Exclusion criteria
1. Any disease associated with immune system impairment, including auto-immune diseases, HIV and transplantation patients;
2. Type 1 or type 2 diabetes mellitus;
3. Any vaccination within the last 3 months;
4. Family history of psoriasis;
5. History of pathological scar formation (keloid, hypertrophic scar);
6. Have any current and / or recurrent pathologically, clinical significant skin condition (including tattoos) at the treatment area (i.e. atopic dermatitis);
7. Hypersensitivity for dermatological marker at screening;
8. Requirement of immunosuppressive or immunomodulatory medication within 30 days prior to enrollment or planned to use during the course of the study;
9. Tanning due to sunbathing, excessive sun exposure or a tanning booth within 3 weeks of enrollment;
10. Participation in an investigational drug or device study within 3 months prior to screening or more than 4 times a year;
11. 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;
12. Current smoker and/or regular user of other nicotine-containing products (e.g., patches).
13. History of or current drug or substance abuse considered significant by the PI (or medically qualified designee), including a positive urine drug screen.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2018-003510-41-NL |
| CCMO | NL67463.056.18 |