Clinical trial NCT03309215: Short Repeated Nickel Exposures
Official title: Evaluation of the Clinical Implication of Short Repeated Nickel Exposures
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Allergic Contact Dermatitis Due to Nickel
Lead sponsor: Herlev and Gentofte Hospital
Sponsor class: OTHER
Collaborators: name: Karolinska Institutet
First posted: 2017-10-13
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The former Nickel Directive was introduced in EU in 1994 limiting the release of nickel from items intended for prolonged contact with skin. The nickel regulation entered into full force in 2001 and became a part of REACH (the EU chemicals regulation) in 2009. Since then the prevalence of nickel allergy has declined in some countries, but not in others, following the implementation. Young individuals still become allergic to nickel (2, 3) and a high prevalence of nickel allergy, exceeding 10%, is seen among young women (below 30 years) in the general population.

The EU nickel regulation has been changing over time. The present limits of nickel release for metallic items intended for direct and prolonged contact with the skin is \<0.5 μg/cm2/week and \<0.2 μg/cm2/week for any post assemblies inserted into pierced holes. In 2014, EU defined prolonged contact with the skin as: at least 30 minutes on one or more occasions within two weeks for items with continuous skin contact, or to at least 10 minutes on three or more occasions within two weeks (7).

The overall objective is to evaluate how well the EU nickel regulation protects individuals against developing nickel dermatitis. More specifically we will:

1. Study the penetration of nickel in normal and irritated skin after short repeated skin exposure under controlled temperature in nickel sensitized patients and in healthy controls
2. Reveal the potential of short repeated nickel skin exposure on normal and irritated skin to elicit dermatitis, during controlled climate factors in nickel sensitized patients and controls using the time restrictions of the definition of prolonged skin contact in the nickel regulation.


Eligibility criteria: For patients with nickel allergy:

Inclusion Criteria:

* Positive patch test to nickel sulphate 5% pet. according to European society of contact dermatitis(ESCD) guidelines within the last 5 years at the Department of Dermatology and Allergy, Gentofte Hospital.
* Age 18-75 years.

Exclusion Criteria:

* Active eczema in test areas
* Generalized eczema
* Scar tissue in test areas.
* Pregnancy or breast feeding
* Treatment with topical corticosteroids or other immune-suppressants on/near test areas within four weeks prior to study start
* Systemic immunomodulatory\* treatment within 4 weeks prior to study start
* UV exposure of test areas within three weeks prior to study start
* Participation in other clinical studies within four weeks prior to study start
* Unable to cooperate or communicate with the investigators \*Systemic immunomodulatory treatment is drugs taken orally or by injection that modify the response of the immune system by increasing (immunostimulators) or decreasing (immunosuppressives) the production of serum antibodies

For Healthy volunteers:

Inclusion Criteria:

* Negative patch test result to nickel sulphate 5% pet. according to ESCD guidelines (48) at the Department of Dermatology and Allergy, Gentofte Hospital
* Age 18-75 years.

Exclusion Criteria:

* History of contact allergy
* Generalized eczema
* Scar tissue in test areas.
* Pregnancy or breast feeding
* Treatment with topical corticosteroids or other immune-suppressants on/near test areas within four weeks prior to study start
* Systemic immunomodulatory treatment within four weeks prior to study start
* UV exposure of test areas within three weeks prior to study start
* Participation in other clinical studies within four weeks prior to study start
* Unable to cooperate or communicate with the investigators

Primary outcomes:
measure: Clinical evaluation of development of dermatitis after stimulation over time
timeFrame: 24 hours and 78 hours post stimulation with nickel discs
measure: Change of baseline blood flow over time after stimulation
timeFrame: 24 hours and 78 hours post stimulation with nickel discs
measure: Nickel skin penetration at different time points after stimulation
timeFrame: Immediate deposition and penetration, 24 hours and 78 hours post stimulation of nickel discs
Secondary outcomes:
Other outcomes:
Locations:
city: Hellerup
country: Denmark
facility: Department of Allergy and Dermatology
Study officials:
affiliation: National Allergy Research Centre, Department of Allergy and Dermatology
name: Malin G Ahlström, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Erfani B, Liden C, Midander K. Short and frequent skin contact with nickel. Contact Dermatitis. 2015 Oct;73(4):222-30. doi: 10.1111/cod.12426. Epub 2015 Jun 18.
citation: Hostynek JJ, Dreher F, Nakada T, Schwindt D, Anigbogu A, Maibach HI. Human stratum corneum adsorption of nickel salts. Investigation of depth profiles by tape stripping in vivo. Acta Derm Venereol Suppl (Stockh). 2001;(212):11-8. doi: 10.1080/000155501753279587.
citation: Emilson A, Lindberg M, Forslind B. The temperature effect on in vitro penetration of sodium lauryl sulfate and nickel chloride through human skin. Acta Derm Venereol. 1993 Jun;73(3):203-7. doi: 10.2340/0001555573203207.
citation: Fullerton A, Hoelgaard A. Binding of nickel to human epidermis in vitro. Br J Dermatol. 1988 Nov;119(5):675-82. doi: 10.1111/j.1365-2133.1988.tb03482.x.