Regulatory Lymphocytes in Patients Treated With Specific Immunotherapy

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pawel Gorski, Ministry of Science and Higher Education, Poland
ClinicalTrials.gov Identifier:
NCT01475188
First received: November 16, 2011
Last updated: November 18, 2011
Last verified: November 2011
  Purpose

The purpose of this study is to determine whether specific subcutaneous immunotherapy affects fractions of regulatory T lymphocytes and histamine H2 receptor expression and ZAP70 in regulatory T lymphocytes.


Condition Intervention Phase
Immunotherapy
Seasonal Allergic Rhinitis
Drug: Allergovit
Other: placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Basic Science
Official Title: Regulatory Lymphocytes (Treg) in the Modulation of Allergic Inflammation in Patients Treated With Specific Immunotherapy.

Resource links provided by NLM:


Further study details as provided by Ministry of Science and Higher Education, Poland:

Primary Outcome Measures:
  • numbers of regulatory T lymphocytes (nTregs) [ Time Frame: Change from the baseline year to the 2nd year of immunotherapy. ] [ Designated as safety issue: No ]
    Numbers of regulatory T cells (nTregs) at baseline year both 6 weeks before the start of the pollen season, at the height of pollen season and 6 weeks after the termination of the pollen season and in the 2nd year of immunotherapy both 6 weeks before the start of the pollen season, at the height of pollen season and 6 weeks after the termination of the pollen.


Secondary Outcome Measures:
  • Expression of zeta chain associated protein (ZAp70) in regulatory lymphocytes (nTregs) [ Time Frame: Change from the baseline year to the 2nd year of immunotherapy ] [ Designated as safety issue: No ]
    Expression of zeta chain associated protein (ZAP70) in regulatory T cells (nTregs) at baseline year both 6 weeks before the start of the pollen season, at the height of pollen season and 6 weeks after the termination of the pollen season and in the 2nd year of immunotherapy both 6 weeks before the start of the pollen season, at the height of pollen season and 6 weeks after the termination of the pollen.

  • Expression of histamine H2 receptor in regulatory lymphocytes (NTregs) [ Time Frame: Change from the baseline year to the second year of immunotherapy ] [ Designated as safety issue: No ]
    Expression of histamine H2 receptor in regulatory T cells (nTregs) at baseline year both 6 weeks before the start of the pollen season, at the height of pollen season and 6 weeks after the termination of the pollen season and in the 2nd year of immunotherapy both 6 weeks before the start of the pollen season, at the height of pollen season and 6 weeks after the termination of the pollen.

  • Rhinoconjunctivitis symptom score [ Time Frame: Change from the baseline year to the second year of immunotherapy ] [ Designated as safety issue: No ]
    Change of the rhinoconjunctivitis symptoms score from the baseline year to the 2nd year of immunotherapy

  • Nasal eosinophilia [ Time Frame: Change from the basline year to the 2nd year of immunotherapy ] [ Designated as safety issue: No ]
    Numbers of eosinophils in nasal lavage during the baseline year both 6 weeks before the start of the pollen season, at the height of pollen season and 6 weeks after the termination of the pollen season and in the 2nd year of immunotherapy both 6 weeks before the start of the pollen season, at the height of pollen season and 6 weeks after the termination of the pollen.

  • Concentration of nitric oxide in exhaled air [ Time Frame: Change from the baseline year to the 2nd year of immunotherapy ] [ Designated as safety issue: No ]
    Concentration of nitric oxide in exhaled air during the baseline year both 6 weeks before the start of the pollen season, at the height of pollen season and 6 weeks after the termination of the pollen season and in the 2nd year of immunotherapy both 6 weeks before the start of the pollen season, at the height of pollen season and 6 weeks after the termination of the pollen.

  • Consumption of rescue medications [ Time Frame: Change from the baseline year to the second year of imunotherapy ] [ Designated as safety issue: No ]
    Comparison of the rescue medication intake during the baseline year and during the treatment


Enrollment: 41
Study Start Date: March 2007
Study Completion Date: December 2010
Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: placebo
20 patients with intermittent allergic rhinitis sensitized to grass pollen allergens
Other: placebo
placebo administered with the same scheme and doses as specific subcutaneous immunotherapy
Active Comparator: Specific subcutaneous immunotherapy
21 symptomatic patients with intermittent allergic rhinitis sensitized to grass pollen allergens
Drug: Allergovit
commercially available grass pollen allergoid (100%), concentration A (1000 TU/ml, therapeutic units/ml)concentration B (10000 TU/ml).Patients were given subcutaneous injections with initial dose of 0.1 ml (concentration A) was increased once a 7 (+7) days until the highest tolerated dose (0.6, concentration B) was reached and SIT was continued with injections once every 4 - 6 weeks up to two years.
Other Name: Allergovit, grass pollen 100%, Allergopharma, Germany

Detailed Description:

Allergy constitutes an important problem worldwide thus effective treatment is crucial for the reduction of symptoms severity, patients' activity and quality of life as well as for the reduction of direct and indirect costs of the disease. Specific allergen immunotherapy (SIT) is a potentially curative and specific method of treatment for allergic diseases, particularly for intermittent allergic rhinitis. Specific subcutaneous immunotherapy induce peripheral tolerance and suppress inflammation in tissue. In periphery, effector T cells unresponsiveness to antigens is mediated mainly by allergen specific regulatory T cells. Regulatory T cells induced peripherally comprise IL-10 producing type 1 regulatory T cells (Tr1) and regulatory T cells subset arising in vitro from CD4+CD25- and in vivo from peripheral memory T cells whereas naturally occurring Tregs (nTregs)originate in thymus and represent about 5% of the peripheral CD4 T cells and constitutively express high levels of the high-affinity IL-2 receptor (CD25hi). They coexpress Forkhead Box Protein P3 (Foxp3), glucocorticoid induced tumor necrosis factor receptor (GITR), cytotoxic T lymphocyte associated antigen (CTLA-4), and display low expression of alpha chain of the IL-7 receptor. Although clinical and immunological outcomes of SIT, that are associated with regulatory T cells functions were profoundly studied, little is known about the molecular mechanisms that are crucial for nTregs activation and function in the course of SIT. Since histamine is a key mediator in allergy that exerts its effect through 4 types of histamine receptors we decided to investigate the expression of histamine 2 receptor, that has potent immunomodulatory properties, in regulatory lymphocytes in patients treated with SIT. Furthermore, since T cell receptor activation is essential for T effector lymphocytes activation we wanted to check the expression of zeta chain associated protein (ZAP70), that constitutes a linker between TCR and lower levels of intracellular downstream signal transduction, in regulatory T cells in the course of SIT.

This is a 3-year prospective, placebo controlled, double blind trial of grass SIT. 41 patients with seasonal allergic rhinitis were randomized to receive SIT (n = 21) or placebo (n = 20) and 15 healthy were included as a control. The primary and secondary outcomes were assessed at baseline and during the treatment period - before the start of the pollen season, at the height of the pollen season and after the end of the pollen season.Results were compared between the treatment year and baseline and between the groups treated with SIT, placebo and healthy control.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • seasonal allergic rhinitis with or without allergic conjunctivitis
  • sensitization to grass pollen allergens (confirmed with skin prick tests, conjunctival provocation test, specific IgE)
  • symptoms of allergic rhinitis with or without conjunctivitis for at least 2 years before the study

Exclusion Criteria:

  • sensitization to allergens, that could interfere with grass pollen
  • asthma
  • cystic fibrosis
  • ciliary dysmotility syndrome
  • bronchiectasis
  • smoking
  • tuberculosis
  • neoplastic disease
  • chronic sinusitis and nasal polyps
  • systemic glucocorticosteroids treatment
  • treatment with immunotherapy in the past
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01475188

Locations
Poland
Department of Pneumonology and Allergy, Medical University of Lodz
Lodz, Poland, 90-153
Sponsors and Collaborators
Ministry of Science and Higher Education, Poland
Investigators
Study Chair: Paweł Górski, Prof, MD, PhD Department of Pneumonology and Allergy, Medical University of Lodz, Poland
  More Information

Publications:

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Pawel Gorski, prof, MD, PhD, Ministry of Science and Higher Education, Poland
ClinicalTrials.gov Identifier: NCT01475188     History of Changes
Other Study ID Numbers: N 402 057 32/1788, 1788/PO1/2007/32
Study First Received: November 16, 2011
Last Updated: November 18, 2011
Health Authority: Poland: Ministry of Health

Keywords provided by Ministry of Science and Higher Education, Poland:
specific subcutaneous immunotherapy
seasonal allergic rhinitis
regulatory lymphocytes
signal transduction
histamine receptor

Additional relevant MeSH terms:
Rhinitis
Rhinitis, Allergic, Perennial
Rhinitis, Allergic, Seasonal
Nose Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Otorhinolaryngologic Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases

ClinicalTrials.gov processed this record on September 22, 2014