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Trial registered on ANZCTR


Registration number
ACTRN12611000543987
Ethics application status
Approved
Date submitted
23/05/2011
Date registered
30/05/2011
Date last updated
6/06/2011
Type of registration
Retrospectively registered

Titles & IDs
Public title
Randomized, double-blind, placebo-controlled clinical trial of sublingual immunotherapy in natural rubber latex allergic patients
Scientific title
Randomized, double-blind, placebo-controlled clinical trial of sublingual immunotherapy in natural rubber latex (NRL) allergic patients
Secondary ID [1] 262241 0
NIL
Universal Trial Number (UTN)
U1111-1121-6078
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Latex allergy 267934 0
Condition category
Condition code
Inflammatory and Immune System 268080 268080 0 0
Allergies

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Sublingual immunotherapy (SLIT) to latex (SLIT latex, ALK-Abello, Madrid, Spain). The SLIT is oral fluid.
The treatment was administered once a day: two drops of SLIT each day. The study was performed in two phases: the first one, double-blind, placebo-controlled during one year; and the second one, also for one year, opened, where every patient received active treatment.
Intervention code [1] 266631 0
Treatment: Other
Comparator / control treatment
Placebo.
The placebo was made of the same dilution liquid (water) used in the active treatment. The active treatment had no taste, and had clear appearance, so no masking was required.
Control group
Placebo

Outcomes
Primary outcome [1] 266818 0
Size of wheal in skin prick test measured by parallel lines assay
Timepoint [1] 266818 0
1, 6, 12, 18 and 24 months
Secondary outcome [1] 276443 0
Conjunctival challenge test.
The difference in the concentration of latex extract needed to obtain 5 points of symptoms in the conjunctival challenge test was compared between placebo and active groups after one year of active treatment and intragroup after one and two years of treatment.
Timepoint [1] 276443 0
0, 12 and 24 months
Secondary outcome [2] 276444 0
Glove use test.
The difference in the time using the latex glove needed to obtain 5 points of symptoms in the glove used test was compared between placebo and active groups after one year of active treatment and intragroups after one and two years of treatment.
Timepoint [2] 276444 0
0, 12 and 24 months
Secondary outcome [3] 276445 0
Basophil Activation Test.
Timepoint [3] 276445 0
0, 12 and 24 months
Secondary outcome [4] 276446 0
Specific IgE determination.
Specific IgE to NRL was measured using commercial uniCAP (Phadia, Sweden) to NRL (k81), and to recombinant main allergenic components of latex (Hev b 1, hev b 3, hev b 5, Hev b 6, and Hev b 8). The results were compared between placebo and active groups after one year of active treatment and intragroups after one and two years of treatment.
Timepoint [4] 276446 0
0, 12 and 24 months

Eligibility
Key inclusion criteria
Inclusion criteria comprised a clinical history of natural rubber latex allergy (documenting the usual symptoms of urticaria, angioedema, rhinitis, conjunctivitis, asthma or anaphylaxis) or a positive response to the gloves use test and/or conjunctival test plus positive prick test to NRL (wheal greater than or equal to 3x3 mm).
Minimum age
24 Years
Maximum age
57 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria consisted of the usual contraindications for the use of immunotherapy and the presence of severe systemic or psychiatric diseases, chronic urticaria or dermographism.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
A randomization table in 4-patient groups was performed. Each patient was assigned to a correlative number. The investigator who included the patients was unaware to which group the subject was allocated.
Allocation was made assigning a correlative number to each patient. Treatments, active and placebo were bought to the laboratory (ALK-Abello). The laboratory created a randomization table, in 4 patient-groups (each 4 correlative patients, 2 were placebo and 2 active) and labelled the treatments with one number. The external appearence of placebo or active treatments were identical.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The manufacturing laboratory generated by means of a computer programme, a random allocation table by 4-item groups.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2 / Phase 3
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 3601 0
Spain
State/province [1] 3601 0
Alava

Funding & Sponsors
Funding source category [1] 267122 0
Government body
Name [1] 267122 0
FIS (PI04/2301)
Address [1] 267122 0
Ministerio de Sanidad y Consumo
Subdireccion General de Investigacion Sanitaria
Sinesio Delgado 6
28029 Madrid
Country [1] 267122 0
Spain
Funding source category [2] 267123 0
Charities/Societies/Foundations
Name [2] 267123 0
Foundation Jesus Gangoiti Barrera 2004
Address [2] 267123 0
Kalea Rodriguez Arias, 23
48011 Bilbao
Country [2] 267123 0
Spain
Funding source category [3] 267124 0
Charities/Societies/Foundations
Name [3] 267124 0
Foundation SEAIC (Spanish Society of Allergy and Clinical Immunology)
Address [3] 267124 0
Gran Via 184, 7, 1
08004 BARCELONA
Country [3] 267124 0
Spain
Funding source category [4] 267125 0
Charities/Societies/Foundations
Name [4] 267125 0
Research Foundation of the Santiago Apostol Hospital
Address [4] 267125 0
C/ Olaguibel, n29 01004 Vitoria - Gasteiz
Country [4] 267125 0
Spain
Primary sponsor type
Hospital
Name
Allergy Service. Hospital Santiago Apostol
Address
C/ Olaguibel, no29 01004 Vitoria - Gasteiz
Country
Spain
Secondary sponsor category [1] 264203 0
Hospital
Name [1] 264203 0
Clinical Assays Unit. Txagorritxu Hospital
Address [1] 264203 0
Hospital Txagorritxu
Jose Atxotegui, s/n.
01009 Vitoria
Country [1] 264203 0
Spain

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 267108 0
Ethics Committee of the Santiago Apostol Hospital
Ethics committee address [1] 267108 0
Hospital Santiago Apostol
Olaguibel, 29
01004 Vitoria, Alava
Ethics committee country [1] 267108 0
Spain
Date submitted for ethics approval [1] 267108 0
Approval date [1] 267108 0
16/07/2003
Ethics approval number [1] 267108 0

Summary
Brief summary
BACKGROUND: Natural rubber latex allergy is still an unsolved health problem. In addition to the recommended avoidance to the allergen, therapeutic measures are needed and therefore so are immunotherapy extracts with proven efficacy and safety.
The aim of the present randomised, double-blind, placebo-controlled clinical trial was to assess the efficacy and tolerability of latex sublingual immunotherapy in adult patients undergoing permanent latex avoidance.
METHODS: Twenty-eight adult latex-allergic patients (5 males and 23 females), with mean age of 39 years (range 24-57) were randomized to receive a commercial latex-sublingual immunotherapy or placebo during one year, followed by another year of open, active therapy. The following outcomes were measured at baseline and at the end of first and second year of follow-up: skin prick test, gloves-use score, conjunctival challenge test, total and specific IgE, basophil activation test, and adverse reactions monitoring.
RESULTS: No significant difference in any of the efficacy in vivo variables was observed between active and placebo groups at the end of the placebo-controlled phase, nor when each group was compared with their baseline values at the end of the two year-study. An improvement in the average percentage of basophils activated was observed. During the induction phase, 4 reactions in the active and 5 in the placebo group were recorded. During the maintenance phase, two patients dropped out due to pruritus and to acute dermatitis respectively.
CONCLUSION: Further studies are needed to evaluate latex-sublingual immunotherapy, since efficacy could not be demonstrated in adult patients with avoidance of the allergen.
Trial website
Trial related presentations / publications
Basophil activation test and challenge tests in natural rubber latex allergy.
Gastaminza G, Uriel O, Sanz ML, Algorta J, Audicana MT, Echenagusia MA, Fernandez E, Bernedo N, Munoz D.
Allergy Clin Immunol Int 2005, suppl 1: 200
XIX World Allergy Congress and XXIV Congress of the EAACI, Munich 26 June-1st July 2005
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First year results of a Randomised, double blind, placebo-controlled clinical trial of sublingual natural rubber latex immunotherapy in latex allergic patients
Gastaminza G, Uriel O, Algorta J, Audicana MT, Fernandez E, Sanz ML, Echenagusia M, Munoz D
Oral communication. Abstract book, 27-28.
XXV Congress EAACI, Viena 10-14 June 2006
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Two-year results of a randomised, double blind, placebo-controlled clinical trial, of sublingual natural rubber latex immunotherapy in latex allergic patients.
G Gastaminza, O Uriel, J Algorta, M Audicana, E Fernandez, M Sanz, Z Abajo, E Santaolalla, D Munoz.
Allergy 2007 (62); suppl 83; 262.
XXVI Congress EAACI, Göteborg (Sweden) 9-13 June 2007
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Public notes

Contacts
Principal investigator
Name 32650 0
Address 32650 0
Country 32650 0
Phone 32650 0
Fax 32650 0
Email 32650 0
Contact person for public queries
Name 15897 0
Gabriel Gastaminza
Address 15897 0
Department of Allergology and Clinical Immunology
Clinica Universidad de Navarra
Pío XII 36
31008 Pamplona
Country 15897 0
Spain
Phone 15897 0
0034948255400
Fax 15897 0
0034948296500
Email 15897 0
gastaminza@unav.es
Contact person for scientific queries
Name 6825 0
Gabriel Gastaminza
Address 6825 0
Department of Allergology and Clinical Immunology
Clinica Universidad de Navarra
Pío XII 36
31008 Pamplona
Country 6825 0
Spain
Phone 6825 0
0034948255400
Fax 6825 0
0034948296500
Email 6825 0
gastaminza@unav.es

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary