To evaluate the diagnostic performance and safety of metal allergens proposed for inclusion in Metal Panel T.R.U.E. Test. The study will compare the diagnostic performance (primary) and safety (secondary) of ascending patch test doses of aluminum,…
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Source
Brief title
Condition
- Epidermal and dermal conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Determination of optimal test allergen dose will be based on the following
criteria:
-The lowest concentration of each dilution series allergen eliciting positive
responses in a minimum of 15 subjects. Positive responses (defined as score of
1+, 2+ or 3+ during at least one reaction assessment visit) may be due to the
dilution series allergen, a corresponding reference allergen or both. If a
significant number of 3+ responses are elicited, the dose will be selected
based on 1+ and 2+ responses.
-Approximately 50% of the 15 positive responses attributed to a dilution series
allergen,
-Moderate to very good concordance (measured using Cohen*s kappa, includes all
subjects who test each allergen) between the dilution series and reference
allergens. [less than 0% no agreement, 0-20% poor, 20-40% fair, 40-60%
moderate, 60-80% good, 80% or higher very good].
Secondary outcome
Determination of allergen safety
-Frequency of tape and polyester chip induced irritation or allergic reactions
at Visits 2 through 6.
-Frequency of subject reported sensations of itching and/or burning for each
allergen panel at patch removal.
-Frequency of positive (1+, 2+, 3+) skin reactions for each investigational and
reference allergen dose at each post removal visit and overall.
-Frequency of negative, doubtful, irritant, late and persistent skin reactions
for each investigational and reference allergen dose at each post removal visit
(late and persistent reactions at visits 4, 5 and 6 only).
-Frequency of adverse events. Documentation for all local and systemic adverse
reactions classified by the investigator as possibly or definitely related to
the study product (e.g., erythema, hyper-pigmentation, hypo-pigmentation, skin
thinning or dermatitis flare) will include grade (mild, moderate or severe) and
time point (clinic visit).
Background summary
As a group, metals are the most common contact allergens. Contact allergy to
metals such as nickel, cobalt, and chromium is prevalent in the general
population. It is estimated that up to 17% of women and 3% of men are nickel
allergic, and that about 1 to 2% are allergic to cobalt, chromium, or both.
Metal-induced allergic contact dermatitis (ACD) is expressed in a wide range of
cutaneous reactions following prolonged or repeated exposure to personal
products such as cosmetics, tattoos, detergents, jewelry, piercing studs,
leather goods, cell phones, clothing buttons, snaps, zippers, partial dentures,
dental braces and restorations. Occupational exposure in the metal and
construction industries is also a significant risk factor for metal allergy
reports. Apart from the well-known significance of nickel, cobalt, chromium and
gold in developing ACD, other metals such as aluminum, beryllium, copper,
iridium, indium, mercury, palladium, platinum, rhodium, molybdenum, manganese,
zinc, cadmium and titanium have been reported as increasing causes of skin
hypersensitivity.
Because metal contact allergy is increasing there is a need to develop a series
of standardized metal patch test allergens utilizing the same allergen delivery
technology as used in the T.R.U.E. TEST* product. Metal Panel T.R.U.E. TEST
will be indicated for patients in whom the physician suspects contact
dermatitis related to:
Cardiac implant (stent, pacemaker, etc.)
Orthopedic implant (knee, hip or other)
Gynecological implant or device
Surgical hardware (plates, screws, wires, pins, rods, expanders, staples)
Dental metal implant
Dental metal appliance, prosthesis or filling
Inflammation associated with an oral metal implant:
Itching, papules or nodules at injection site of aluminum containing
vaccination
Dermatitis over site of metal implant
Systemic contact dermatitis
Accelerated restenosis of cardiac stent
Aseptic loosening
Persistent joint pain
Other symptoms may also be associated:
Persistent and recalcitrant dermatitis
Dorsal or patchy hand dermatitis
Leg and foot dermatitis
Facial dermatitis (excluding seborrheic)
Discoid dermatitis
Dermatitis with unusual distribution
Atypical allergic symptoms
Study objective
To evaluate the diagnostic performance and safety of metal allergens proposed
for inclusion in Metal Panel T.R.U.E. Test. The study will compare the
diagnostic performance (primary) and safety (secondary) of ascending patch test
doses of aluminum, copper, manganese, molybdenum, tin, titanium, vanadium and
zinc allergens.
To determine if subjects who have not had previous patch testing are allergic
to any of the most common metal allergens; nickel, cobalt chromium and gold.
Study design
This is a prospective, multi-center, double-blind randomized design. A 48-hour
application (approximate) of investigational allergen panel(s), an excipient
control and corresponding reference petrolatum allergen(s) will be applied to
the skin of human subjects to test for potential positive allergic responses.
Test sites will be evaluated at 3-4, 7-8, 10-14 and 19-23 days after
application. The chosen evaluation times are consistent with generally accepted
international patch test guidelines and are designed to prevent missed late
reactions and false negatives. The final clinic visit (day 21) allows the
investigator to evaluate any late or persistent localized reactions. The
investigator may choose to perform this visit via telephone if there are no
residual reactions. If there are persistent escalating reactions noted at Visit
6, the investigator will determine and record follow up action.
Intervention
Ascending patch test doses and a reference allergen will be applied to the
upper backs of the study subjects and removed after two days. Test site skin
reactions will be evaluated at least four times which is consistent with
generally accepted international patch test guidelines designed to prevent
missed late reactions and false negatives.
During the first 2 days of the study, test sites and patch test panels must
remain dry and protected. Activities that involve excess moisture (sweat or
water), movement, or sun exposure must be avoided. After panel removal, and
until the final 3-week visit, subjects must protect test sites from sun,
irritation, medicaments, and foreign or harsh substances.
Investigational panels will be produced with ascending doses of allergen and an
excipient control. These dose ranges were selected based on published studies
of patch testing with the metals and available non-standardized patch test
products currently available in the U.S. and Europe.
Investigational allergen panels are packed and labeled by the manufacturer
SmartPractice Denmark ApS. Products are labeled with allergen batch codes and
expiration dating. Commercially available reference allergens may be used or
the reference allergen syringes may be prepared and labeled by the Department
of Occupational and Environmental Dermatology, Skåne University Hospital,
Malmö, Sweden.
All investigational products used in this study must be accounted for. Records
must show amount and date of delivery of all test materials to each local
investigator. Likewise dates, amount, and signatures should document return of
unused test tapes. Product deliberately and/or accidentally destroyed by the
investigator must also be documented.
The use of the investigational product for the individual subject, including
the subject number, date of application of the test panel, and date of removal
of the test panel will be documented in the Case Report Form
Study burden and risks
The patch test is considered to be a safe and optimum method to identify the
cause of allergic contact dermatitis when performed and interpreted correctly.
Evaluations regarding the safety of the T.R.U.E. Test product has been based
primarily on the scientific and medical literature in addition to clinical
trials conducted by Smart Practice and SmartPractice Denmark (previously Mekos
Laboratories AS). After many years of extensive patch testing, no data has
evolved to indicate there are any significant safety concerns or long-term
adverse effects to human tissue other than the expected allergic response in a
sensitized individual.
The elicitation of a specific immunologic inflammatory response at the test
site (forearm or back) on re-exposure to a specific allergen, is the expected
reaction and the basis for this diagnostic patch test method. This response is
expected to manifest 24 to 72 hours in a previously sensitized individual.
Patch testing aims to reproduce (on a small scale) the eczematous response of
the patient when in contact with the suspect allergen(s).
Patch tests are typically applied to the skin of the upper back. The humidity
of the skin hydrates the allergen, allowing it to migrate into the skin,
thereby reaching the cells of the immune system. The test is removed after 48
hours and read at 72-96 hours after the application, when the allergic
responses are fully developed and mild irritant reactions have faded.
Additional readings at 1 week and 21 days after panel placement are also
advised in some cases.
Site reactions are graded according to standard patch testing guidelines
established by the International Contact Dermatitis Research Group.
The following reactions, although exceedingly rare, have been reported. Unless
all 3 SUSAR criteria are met, these reactions will be reported as adverse
events.
-Active Sensitization: A positive reaction observed 7-14 days after
application, with no preceding reaction. The positive reaction must meet the
criteria for an allergic reaction (papular or vesicular erythema and
infiltration), to help distinguish between a false-positive and sensitization.
-Bacterial or Viral Infections: An inflammation due to a skin infection.
-Ectopic Flare: A positive patch test reaction accompanied by a flare of an
existing or pre-existing dermatitis that was caused by the test allergen.
-Excited Skin Syndrome (Angry Back): A state of skin hyper-reactivity induced
by dermatitis on other parts of the body or by a strong positive skin-test
reaction in which other patch test sites become reactive, especially to
marginal irritants.
-Immediate Contact Urticaria (ICU): Some allergens can cause ICU (balsam of
Peru, cinnamic aldehyde, neomycin, bacitracin) with the typical wheal and flare
appearing 30- 40 minutes after application. The reaction only occurs in
individuals who are pre-sensitized. Non-allergic urticaria is possible in
non-sensitized individuals and is less serious because the systemic reactions
are not evoked. Most non-allergic reactions remain local while ICU may produce
generalized urticarial lesions. Most urticarial reactions, reported in
conjunction with patch testing, are due to higher concentrations of the
allergen (e.g. 5% pet).
-Koebner Phenomenon: A positive patch test reaction in a patient with active
psoriasis or lichen planus may reproduce these dermatoses at the patch site
during the weeks after testing. Symptoms are cleared with topical
corticosteroids.
-Necrosis, Scarring and Keloids: Testing with strong irritants (acids, alkalis
or chemicals of unknown composition) may produce such adverse events but are
considered extremely rare.
-Pressure Effect: Application of a patch test in certain individuals, which
produces an edematous area that is typically most intense at the margins.
Dermatographic individuals are more likely to develop this reaction.
East McDowell Road 3400
Phoenix 85008
US
East McDowell Road 3400
Phoenix 85008
US
Listed location countries
Age
Inclusion criteria
a. 18 years of age or older.
b. Past positive patch test result within the past 10 years (to one of the dilution series metals being tested on this study), a strong suspicion of metal contact allergy, or known or suspected infection of the skin, joints and other sites associated with metal exposure as listed in the Qualification Questionnaire.
c. Unable to become pregnant or willing to use an acceptable method of contraception to prevent pregnancy if female of childbearing potential (Inability to become pregnant would include all male subjects and female subjects who are postmenopausal for at least 1 year, or surgically sterile- have had a hysterectomy, bilateral ovariectomy, uterine ablation or bilateral tubal ligation. Acceptable methods of contraception include: 1) systemic birth control; 2) double barrier method; 3) IUD; 4) vasectomized partner; or 5) abstinence from sexual intercourse. Subject must agree to use acceptable contraception for the duration of the entire study.)
d. Understands and signs the approved Informed Consent form which is consistent with all institutional, local and national regulations.
Exclusion criteria
a. Breastfeeding or pregnant (as determined by urine pregnancy test) or intending to become pregnant during the course of the study.
b. Topical treatment with corticosteroids or other immunosuppressive agents on or near the test area 14 days prior to inclusion through the end of the subject*s participation in the study.
c. Systemic treatment with corticosteroids (equivalent to > 10 mg prednisone) or other immunosuppressive agents 14 days prior to inclusion through the end of the subject*s participation in the study. Inhaled treatments and steroidal nose or eye drops are permitted.
d. Treatment with ultraviolet (UV) light (including tanning) during the 3 weeks prior to inclusion through the end of the subject*s participation in the study.
e. Acute dermatitis outbreak or dermatitis on or near the test area on the back.
f. Known or suspected infection of the skin, joints or other site(s) associated with metal exposure
g. Condition such as; fibromyalgia, chronic fatigue, depression, cognitive impairment, flu-like symptoms, diarrhea and/or headache without at least one of the symptoms related to metal exposure listed in Section 10.1 under physical examination.
h. Condition such as; psoriasis, dermatitis herpetiformis, mycosis fungoides or cutaneous T-cell lymphoma that may confound the evaluation of allergic contact dermatitis.
i. Inability to comply with patch test study requirements including multiple return visits and activity restrictions (e.g., protecting test panels from excess moisture due to showering or vigorous activity).
j. Participation in a clinical trial of an investigational drug, treatment or device during this study or 3 weeks prior to inclusion in this study.
k. An opinion of the Investigator that deems the potential subject to be non-compliant, unable to return for study visits or complete the study as detailed in the protocol.
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 | EUCTR2015-002678-19-NL |
| ClinicalTrials.gov | NCT02615249 |
| CCMO | NL57210.029.16 |