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Systemic Inflammatory Response to CCRE (Endoscreen)

2019年9月18日 更新者：University of North Carolina, Chapel Hill

Systemic Inflammatory Response to 20,000 EU Clinical Center Reference Endotoxin in Normal Adults

Purpose: The purpose of this study is to classify volunteers as endotoxin-responders or non-responders following inhalation of 20,000 EU Clinical Center Reference Endotoxin (CCRE). Endotoxin is a commonly encountered bioaerosol and component of indoor and outdoor air pollution. For reasons that remain unclear, some individuals appear to be more susceptible to the inflammatory effects of inhaled endotoxin than are others, possibly owing to single nucleotide polymorphisms in the Toll-like receptor 4 (TLR4) gene that influence TLR4 signaling and function. These susceptible individuals represent a population of particular interest for further mechanistic studies of the effects of endotoxin and for therapeutic trials. Susceptibility to inhaled endotoxin will be determined by measuring change in peripheral blood neutrophil counts, a biomarker of systemic inflammation, following inhaled CCRE. In our previous work, the investigators have found that inhalation of 20,000 EU CCRE is well tolerated and induces measurable increase in neutrophil content of peripheral blood in susceptible individuals. Our hope is that this CCRE inhalation protocol can be employed to screen large populations for susceptibility to the inflammatory effect of inhaled endotoxin.

調査の概要

状態

完了

条件

介入・治療

詳細な説明

This is a single center, screening study involving recruitment of 18 normal volunteers (NV). The protocol is powered to compare absolute neutrophil count (ANC) in the blood 6 hours after inhalational challenge with CCRE compared baseline. In addition, as secondary endpoints, the investigators will evaluate inflammatory cytokine levels in systemic circulation and access for the presence of genes thought to be related to endotoxin response. Visits will be conducted by a study coordinator or other study staff, physical exams will be performed by the PI or other study physician.

Eighteen subjects will be recruited. There will be no gender or ethnic restrictions, and subjects will be healthy volunteers. Prior to enrollment in this study, subjects will have participated in our protocol 98-0799 (screening and database study for the CEMALB). Data such as medical history and allergy skin testing collected during the screening protocol will be included with data in this study. Subjects with positive allergy skin testing will not be excluded. Spirometry will be performed to determine the current level of lung function.

In order to identify those individuals who appear more susceptible to the systemic inflammatory effects of endotoxin exposure, subjects will undergo inhaled endotoxin challenge at the baseline visit followed 6 hours later by blood draw for complete blood count with differential to allow for calculation of absolute neutrophil count (ANC). Subjects will be considered "responders" if their peripheral ANC increases by at least 20% following inhaled endotoxin challenge.

研究の種類

介入

入学 (実際)

25

段階

  • フェーズ 1

連絡先と場所

このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。

研究場所

  • アメリカ
    • North Carolina
      • Chapel Hill、North Carolina、アメリカ、27599
        • Environmental Protection Agency Human Studies facility

参加基準

研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。

適格基準

就学可能な年齢

18年～50年 (大人)

健康ボランティアの受け入れ

はい

受講資格のある性別

全て

説明

Inclusion Criteria:

  1. Subjects must be 18-50 years of age to be eligible for study participation
  2. Subjects must be willing to and able to provide informed consent and participate in all study procedures

  3. Normal lung function, defined as (Knudson 1976/1984 predicted set):

    • 1. Forced Vital Capacity (FVC) of > 80% of that predicted for gender, ethnicity, age and height
    • 2. Forced Expiratory Volume in the first second (FEV1) of > 80% of that predicted for gender, ethnicity, age and height
    • 3. FEV1/FVC ratio of > 0.75 of that predicted for gender, ethnicity, age and height
  4. Oxygen saturation of > 94% Normal blood pressure (Systolic between 150 - 90, Diastolic between 90-60 mm Hg)
  5. Symptom Score (defined in section "f") no greater than 6 (out of a possible 24) for total symptom score with a value no greater than 2 for any one score.

Exclusion Criteria:

  1. Any chronic medical condition considered by the PI as a contraindication to the exposure study including significant cardiovascular disease, diabetes requiring medication, chronic renal disease, or chronic thyroid disease.
  2. Physician directed emergency treatment for asthma exacerbation within the preceding 3 months.
  3. Moderate or Severe asthma
  4. Exacerbation of asthma more than 2x/week that would be characteristic of a person of moderate or severe persistent asthma as outlined in the current NHLBI guidelines for diagnosis and management of asthma.
  5. Nighttime symptoms of cough or wheeze greater than 1x/week at baseline (not during a clearly recognized viral induced asthma exacerbation) which would be characteristic of a person of moderate or severe persistent asthma as outlined in the current NHLBI guidelines for diagnosis and management of asthma
  6. Daily requirement for albuterol due to asthma symptoms (cough, wheeze, chest tightness) which would be characteristic of a person of moderate or severe persistent asthma as outlined in the current NHLBI guidelines for diagnosis and management of asthma. (Not to include prophylactic use of albuterol prior to exercise).
  7. History of intubation for asthma
  8. Daily use of NSAIDs, or inability to withhold NSAIDs for 4 days prior to dosing.
  9. Use of medications that may impact the results of the study to include, but not limited to, systemic corticosteroids, beta blockers.
  10. Cigarette smoking > 1 pack per month.
  11. BMI>35.
  12. Pregnant or breast feeding women will not be included.
  13. Subjects who are employed within the past 6 months in an occupation with high risk for endotoxin exposure, such as grain storage sites or swine containment.

  14. Subjects will be deferred after any acute, non-chronic medical condition requiring treatment, such as bronchitis, pneumonia or febrile illness for a minimum of 4 weeks after complete resolution of symptoms.

    -

研究計画

このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。

研究はどのように設計されていますか？

デザインの詳細

  • 主な目的：他の
  • 割り当て：なし
  • 介入モデル：単一グループの割り当て
  • マスキング：なし（オープンラベル）

武器と介入

参加者グループ / アーム
介入・治療
実験的：CCRE
20,000 EU of CCRE (Clinical Center Reference Endotoxin)
薬：CCRE
Endotoxin challenge: Subjects will undergo inhalation of 20,000 EU CCRE. The CCRE will be inhaled by subjects as a nebulized preparation using an ultrasonic nebulizer until the challenge solution is completely spent (generally 10 minutes).
他の名前：
  • endotoxin, lipopolysaccharide (LPS)

この研究は何を測定していますか？

主要な結果の測定

結果測定
メジャーの説明
時間枠
Change in peripheral blood PMNs
時間枠：6 hrs post exposure
The objective of this study is to identify endotoxin responders, characterized by an increase in post-CCRE peripheral blood polymorphonuclear (PMN)s compared to that day's baseline values of > 20%. Thus, there will be two data points for this cohort, blood PMNs at baseline and PMNs 6 hours following 20,000 endotoxin units (EU) of CCRE.
6 hrs post exposure

協力者と研究者

ここでは、この調査に関係する人々や組織を見つけることができます。

スポンサー

University of North Carolina, Chapel Hill

協力者

Environmental Protection Agency (EPA)

捜査官

  • 主任研究者：Michelle Hernandez, MD、UNC

研究記録日

これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。

主要日程の研究

研究開始 (実際)

2017年12月11日

一次修了 (実際)

2019年8月6日

研究の完了 (実際)

2019年8月6日

試験登録日

最初に提出

2016年7月25日

QC基準を満たした最初の提出物

2016年7月25日

最初の投稿 (見積もり)

2016年7月28日

学習記録の更新

投稿された最後の更新 (実際)

2019年9月20日

QC基準を満たした最後の更新が送信されました

2019年9月18日

最終確認日

2019年9月1日

詳しくは

本研究に関する用語

キーワード

その他の研究ID番号

  • 15-1458

個々の参加者データ (IPD) の計画

個々の参加者データ (IPD) を共有する予定はありますか?

いいえ

IPD プランの説明

for internal analysis only

医薬品およびデバイス情報、研究文書

米国FDA規制医薬品の研究

はい

米国FDA規制機器製品の研究

いいえ

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