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CompletedNCT03309215Updated Feb 11, 2020

Short Repeated Nickel Exposures

An interventional study of Experimental stimulation with nickel discs in Allergic Contact Dermatitis Due to Nickel, sponsored by Herlev and Gentofte Hospital. Completed at 1 site in Denmark. Open to participants aged 18 Years to 75 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2020-02-11.

Sponsored by Herlev and Gentofte Hospital · Not applicable, Interventional, and Prevention

Phase
Not applicable
Study type
Interventional
Enrollment
30
Allocation
Randomized
Ages
18 Years to 75 Years
Sex
All
01

Study 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.
02

Conditions studied

  • Allergic Contact Dermatitis Due to Nickel
03

Who can participate

Ages eligible
18 Years to 75 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

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
04

Study design

Phase
Not applicable
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
30 participants (actual)

Study arms

  • Experimental
    Patients with nickel allergy

    Experimental stimulation with nickel discs

    Other: Experimental stimulation with nickel discs

  • Experimental
    Persons without nickel allergy

    Experimental stimulation with nickel discs

    Other: Experimental stimulation with nickel discs

Interventions

  • OtherExperimental stimulation with nickel discs

    All participants will be exposed to 8 metal discs, 3 cm in diameter, 4 on each arm, placed on the volar side of the forearms (figure 1). Three of the metallic discs consists of \>99 wt.% nickel one consist of \>99wt.% Aluminium.The latter is used as a negative control. The discs will be applied under occlusion and with initial pressure and friction. One metallic disc with nickel, and one with aluminium, will be randomized for the earlobes on the patients with nickel allergy

05

What researchers measure

Primary outcomes

  1. Clinical evaluation of development of dermatitis after stimulation over time

    Development of dermatitis after stimulation with nickel discs as a change from baseline skin assessment. The criteria developed by the International Contact Dermatitis Research Group (ICDRG), later modified by Hindsén and Bruze will be used for assessment

    Time frame: 24 hours and 78 hours post stimulation with nickel discs

  2. Change of baseline blood flow over time after stimulation

    measure blood flow with laser doppler technique as a surrogate for inflammation on skin following stimulation with nickel discs over time

    Time frame: 24 hours and 78 hours post stimulation with nickel discs

  3. Nickel skin penetration at different time points after stimulation

    by using the tape stripping technique we will measure the deposition of nickel and the penetration of nickel in the stratum corneum following stimulation

    Time frame: Immediate deposition and penetration, 24 hours and 78 hours post stimulation of nickel discs

06

Study locations

1 site
  • Department of Allergy and Dermatology
    Hellerup, 2900, Denmark
07

References and documents

Publications

  • 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. PubMed 26086991 ↗
  • 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. PubMed 11802472 ↗
  • 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. PubMed 8105620 ↗
  • 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. PubMed 3207621 ↗

Individual participant data

Plan to share: Undecided

08

Registry details

Key details

Study ID
NCT03309215
Lead sponsor
Herlev and Gentofte Hospital
Collaborators
Karolinska Institutet
Responsible party
Malin Glindvad Ahlström (MD, Ph.d.-student, Herlev and Gentofte Hospital) — Principal investigator
First posted
Oct 13, 2017
Start date
Sep 16, 2017
Primary completion
Dec 10, 2017
Completion
Dec 10, 2017
Last update
Feb 11, 2020

Study contacts

Malin G Ahlström, MD
principal investigator · National Allergy Research Centre, Department of Allergy and Dermatology

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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