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Pilot Study: Characterization of the Immune Phenotype of Patients Allergic to Wasp Venom or Penicillin (WasPenIP)

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ClinicalTrials.gov Identifier: NCT03219827
Recruitment Status : Recruiting
First Posted : July 18, 2017
Last Update Posted : January 28, 2019
Sponsor:
Information provided by (Responsible Party):
Institut Pasteur

Brief Summary:
Severity of allergic reactions are highly variable from one individual to another, they can range from absent to life threatening. Allergic manifestations and specifically those of anaphylactic reactions are generally attributed to an IgE-dependent activation of mast cells and/or basophils followed by the release of histamine. Recently however evidence accumulated that other pathways might similarly contribute or even trigger anaphylaxis. Moreover, while the variance in human populations is an important subject to scientific research, medical practices and public health policies typically take a 'one for all' approach to disease management and drug development. Indeed, individual heterogeneity in the immune response can have a big impact on the likelihood to respond to therapy. Because of the complexity of immune responses in the individual and within the population, it has not been possible thus far to define the parameters (genetic or environmental) that define the immune system of allergic patients and its natural occurring variability. Thanks to the efforts that have been made in the framework of the Labex "Milieu Intérieur" study genetic, immunological and environmental factors have been identified that can be linked to the heterogeneity of immune responses in healthy individuals. By comparing these already available data from healthy individuals to a novel cohort of patients with defined severe allergic manifestations, we will be able to identify for the first time immunological and environmental parameters that are common to patients with severe allergies and identify those parameters that distinguish allergic patients from the healthy donor cohort. This analysis will thus open new perspectives on deregulated immune pathways in allergic patients allowing to orient future treatment approaches. Furthermore, comparing immune responses before and after allergen-specific immunotherapy will help understanding, which changes in immune responses are causal to a successful treatment. Importantly, this analysis will shed light on the individual differences that may predict the outcome of treatment approaches and propose novel markers of its success.

Condition or disease Intervention/treatment Phase
Allergy Other: Human biological samples Not Applicable

Detailed Description:
Severity of allergic reactions are highly variable from one individual to another, they can range from absent to life threatening. Allergic manifestations and specifically those of anaphylactic reactions are generally attributed to an IgE-dependent activation of mast cells and/or basophils followed by the release of histamine. Recently however evidence accumulated that other pathways might similarly contribute or even trigger anaphylaxis. Moreover, while the variance in human populations is an important subject to scientific research, medical practices and public health policies typically take a 'one for all' approach to disease management and drug development. Indeed, individual heterogeneity in the immune response can have a big impact on the likelihood to respond to therapy. Because of the complexity of immune responses in the individual and within the population, it has not been possible thus far to define the parameters (genetic or environmental) that define the immune system of allergic patients and its natural occurring variability. Thanks to the efforts that have been made in the framework of the Labex "Milieu Intérieur" study genetic, immunological and environmental factors have been identified that can be linked to the heterogeneity of immune responses in healthy individuals. By comparing these already available data to a novel cohort of patients with defined severe allergic manifestations, we will be able to identify for the first time immunological and environmental parameters that are common to patients with severe allergies and identify those parameters that distinguish allergic patients from the healthy donor cohort. This analysis will thus open new perspectives on deregulated immune pathways in allergic patients allowing to orient future treatment approaches. Furthermore, comparing immune responses before and after allergen-specific immunotherapy will help understanding, which changes in immune responses are causal to a successful treatment. Importantly, this analysis will shed light on the individual differences that may predict the outcome of treatment approaches and propose novel markers of its success. Hence, it will give important insights for the individually adapted treatment of patients.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 63 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Pilot Study: Characterization of the Immune Phenotype of Patients Allergic to Wasp Venom or Penicillin
Actual Study Start Date : June 13, 2017
Estimated Primary Completion Date : December 29, 2019
Estimated Study Completion Date : July 29, 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Penicillins

Arm Intervention/treatment
Experimental: Patients allergic to wasp venom

Patient with major allergic reaction to wasp venom.

  • Blood samples collection at visit 1, at visit 2 (4 weeks after visit 1), at visit 3 (one year after treatment onset)
  • After visit 1, an allergen-specific immunotherapy will be conducted as part of the classical patient care program.
Other: Human biological samples
Blood samples collection

Experimental: Patients allergic to penicillin

Patient with major allergic reaction to penicillin.

- Blood samples collection at visit 1 and at visit 2 (4 weeks after visit 1= end of study, none treatment will be evaluated in this arm)

Other: Human biological samples
Blood samples collection




Primary Outcome Measures :
  1. Immune phenotype of allergic patients [ Time Frame: 3 years ]
    Determination of the immune phenotype of allergic patients through flow cytometric analysis of major blood cell populations

  2. Immune phenotype of allergic patients by determination of cytokine/chemokine levels [ Time Frame: 3 years ]
    Measurement of cytokine/chemokine levels in whole bood following stimulation with 6 immune stimulators.


Secondary Outcome Measures :
  1. Differences in immune responses before and after immunotherapy measured by flow cytometric analysis. [ Time Frame: 3 years ]
    Differences between immune responses between patients before and after allergic -specific immunotherapy and between cured and non-cured patients measured by flow cytometric analysis

  2. Differences in immune responses before and after immunotherapy [ Time Frame: 3 years ]
    Differences between immune responses between patients before and after allergic -specific immunotherapy and between cured and non-cured patients measured by cytokine/chemokine levels in whole bood following stimulation with 6 immune stimulators.

  3. Antibody repertoire determination measured by antigen specific ELISA. [ Time Frame: 3 years ]
    Antibody repertoire in wasp venom allergic patients before and after allergen-specific immunotherapy. To determine changes in antigen recognition and subclass composition we will perform antigen specific ELISA.



Information from the National Library of Medicine

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, Learn About Clinical Studies.


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Ages Eligible for Study:   20 Years to 69 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Allergic subjects having done either an allergic reaction at least of grade 3 according to Müller1 or a quincke edema in response to a wasp sting or penicillin intake, otherwise considered as healthy by the investigator based on medical history, clinical examination and laboratory results (blood sampling for laboratory assessments should be done at V0 and only after signed informed consent).
  • Subjects who, according to the investigator, can and will comply with the requirements of the protocol and are available for all scheduled visits at the investigational site.
  • Wasp or penicillin allergic but otherwise healthy male and female aged between 20 and 69 years.
  • 18.5 <= BMI >= 32 kg/m2
  • Ability to give their consent in writing
  • Must understand spoken and written French
  • Affiliated to the French social security or assimilated regimes

Exclusion Criteria:

  • Subjects who cannot participate according to their status on the registry mentioned at Art L.1121-16 of the French Public Health Code
  • Participation in another Clinical study in the last 3 months in which the subject has been exposed to an investigational product (pharmaceutical product or placebo or medical device) or concurrent participation in another clinical study during the study period
  • Travel in (sub-)tropical countries within the last 3 months
  • For women: pregnant or breastfeeding or intending to become pregnant or peri-menopausal
  • Any physical exercise within the last 8 hours before inclusion (V1) and before (V2)
  • Presence of evidence of neurological or psychiatric diagnoses which, although stable, are deemed by the investigator to render the potential patient unable/unlikely to participate in the study satisfactorily.
  • Severe/chronic/recurrent pathological conditions,
  • Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within the 6 months prior to the V0, V1 or V2. For corticosteroids, this will mean a dose equivalent to 20 mg/day of prednisone or equivalent for > 2 weeks (inhaled and topical steroids allowed)
  • Chronic administration of NSAIDs, including aspirin: prolonged intake (> 2 weeks) within 6 months before [exception for low dose aspirin: maximum 250mg/daily, see 5.1]
  • Receipt of any vaccination 3 months before the inclusion or planning to receive any vaccination during the study
  • Receipt of blood products or immunoglobulins within 3 months prior the inclusion or planning to receive blood products or immunoglobulins during the study
  • Hemoglobin measurement less than 10.0 g/dL for women and less than 11.5 g/dL for men
  • Platelet count less than 120.000/mm3
  • ALAT and/or ASAT > 3 times the upper limit of the norm (ULN)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03219827


Contacts
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Contact: Friederike Jönsson 1 44 38 91 44 ext +33 friederike.jonsson@pasteur.fr

Locations
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France
Centre Medical de l'Institut Pasteur Recruiting
Paris, France, 75015
Contact: Nhan Pham Thi    01 40 61 32 36    nhan.pham-thi@pasteur.fr   
Service de Pneumologie Hôpital Bichat Recruiting
Paris, France, 75018
Contact: Catherine Neukirch, Dr       catherine.neukirch@aphp.fr   
Sponsors and Collaborators
Institut Pasteur
Investigators
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Principal Investigator: Nhan Pham Thi Centre Medical de l'Institut Pasteur

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Responsible Party: Institut Pasteur
ClinicalTrials.gov Identifier: NCT03219827     History of Changes
Other Study ID Numbers: 2016-036
First Posted: July 18, 2017    Key Record Dates
Last Update Posted: January 28, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Penicillins
Anti-Bacterial Agents
Anti-Infective Agents