此页面是自动翻译的,不保证翻译的准确性。请参阅 英文版 对于源文本。

Evaluation of Anti-Hemagglutinin (Anti-HA) Antibodies as Protection From the Flu in Healthy People

Evaluation of Anti-Hemagglutinin Antibodies as a Correlate of Protection in an H1N1 Influenza Healthy Human Challenge Model

Background:

- Researchers want to know if a certain type of antibody in the blood affects whether people get influenza (the flu). They will study 2 different groups with different levels of anti-HA antibodies and expose them to the flu virus. They will study how the flu develops in a healthy person. This may lead to future studies to develop new vaccines and treatments for the flu.

Objective:

- To study how people can be protected from flu infection.

Eligibility:

- Healthy volunteers 18 to 50 years of age.

Design:

  • Participants will be screened through the use of a medical history, physical exam, and laboratory tests.
  • Groups of 7 participants will stay in an isolation unit in a hospital for at least 9 days with no visitors.
  • Participants will be screened again upon admission. They will also have:
  • ECG: soft electrodes will be stuck to the skin. A machine will record the heart s electrical signals.
  • Echocardiogram: a small probe will be held to the chest to take pictures of the heart.
  • Lung tests: participants will blow into a machine.
  • They will also have nasal fluid collected. This will be done either with a swab or with a tube of water washing out the nose. This will be done once every day.
  • The flu virus will be sprayed into the participant s nose. This will be done only once.
  • Participants will complete a questionnaire on day 1 and twice a day after that for 14 days.
  • A medical team will watch participants 24 hours a day. They will go home after 2 days of negative flu tests.
  • Participants will have 4 follow-up visits over 8 weeks.

研究概览

地位

完全的

条件

详细说明

The high morbidity and mortality associated with both pandemic and seasonal influenza, and the threat of new pandemic strains emerging, continues to keep influenza at the forefront of infectious disease and public health research. Mean annual estimates of influenza deaths due to seasonal influenza alone, attributes 36,000 deaths in the US and 250,000 to 500,000 deaths in industrialized countries to influenza. Pandemics can have an even more devastating effect, and we must continue to be prepared by making attempts to reduce the public health impact of this important virus.

Currently, influenza vaccination is the cornerstone of prophylaxis and most effective method available to reduce the impact of influenza on the world s population each year. Data from the 2013 influenza season suggest that current seasonal vaccines held to these standards are greatly underperforming especially in those that really need protection such as the elderly, young, and infirmed.

Multiple factors could play a role in defining the true correlates of protection to influenza infection and disease and many of these factors are yet to be clearly defined. In our own influenza challenge study, protocol 12-I-0077, we have clearly seen evidence that not everyone with a low HAI titer is susceptible to influenza, and that there must be other factors protecting certain individuals. There are many examples like this that demonstrate that there may be much more to immune protection to influenza than just anti-HA antibodies.

Live virus challenge studies have played an important role in defining the correlates of protection of influenza in the past, and we believe they can continue to do so in the future. Since the last time a wild-type influenza challenge has been performed to investigate correlates of protection over 20 years ago, many new scientific tools and a significant increase in knowledge of the immune system have developed. In this study we will enroll participants at different hemagglutinin inhibition titer levels and evaluate this as a correlate of protection to the 2009 H1N1 while exploring the other possible correlates of protection that may be identified. This study represents the first opportunity to examine the correlates of protection of influenza in a fully validated and described wild-type virus challenge model. We believe that studies like this are an ideal use of a wild-type influenza challenge study and can lead to intelligent universal vaccine design as well as a basis to begin evaluating novel vaccine strategies in wild-type challenge studies in the future.

研究类型

介入性

注册 (实际的)

74

阶段

  • 阶段2
  • 阶段1

联系人和位置

本节提供了进行研究的人员的详细联系信息,以及有关进行该研究的地点的信息。

学习地点

    • Maryland
      • Bethesda、Maryland、美国、20892
        • National Institutes of Health Clinical Center, 9000 Rockville Pike

参与标准

研究人员寻找符合特定描述的人,称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

18年 至 50年 (成人)

接受健康志愿者

是的

有资格学习的性别

全部

描述

-INCLUSION CRITERIA:

  1. Greater than or equal to 18 and less than or equal to 50 years of age.
  2. Agrees to not use tobacco products during participation in this study.
  3. Willingness to remain in isolation for the duration of viral shedding (at a minimum 9 days) and to comply with all study requirements.
  4. A female participant is eligible for this study if she is not pregnant or breast feeding and 1 of the following:

    • Of nonchildbearing potential (i.e., women who have had a hysterectomy or tubal ligation or are postmenopausal, as defined by no menses in greater than or equal to 1 year).
    • Of childbearing potential but agrees to practice effective contraception or abstinence for 4 weeks prior to and 8 weeks after administration of the influenza challenge virus. Acceptable methods of contraception include 1 or more of the following: 1) male partner who is sterile prior to the female participant s entry into the study and is the sole sexual partner for the female participant; 2) implants of levonorgestrel; 3) injectable progestogen; 4) an intrauterine device with a documented failure rate of < 1%; 5) oral contraceptives; and 6) double barrier methods including diaphragm or condom with a spermicide.
  5. Willing to have samples stored for future research.
  6. Prechallenge serum hemagglutination inhibition (HAI) titer against the challenge virus of greater than or equal to 1:40 or less than or equal to 1:10 during a screening visit in protocol #11-I-0183
  7. HIV uninfected.

EXCLUSION CRITEIRA:

  1. Presence of self-reported or medically documented significant medical condition including but not limited to:

    1. Chronic pulmonary disease (e.g., asthma, emphysema).
    2. Chronic cardiovascular disease (e.g., cardiomyopathy, congestive heart failure, cardiac surgery, ischemic heart disease, known anatomic defects).
    3. Chronic medical conditions requiring close medical follow-up or hospitalization during the past 5 years (e.g., diabetes mellitus, renal dysfunction, hemoglobinopathies).
    4. Immunosuppression or ongoing malignancy.
    5. Neurological and neurodevelopmental conditions (e.g., cerebral palsy, epilepsy, stroke, seizures).
    6. Postinfectious or postvaccine neurological sequelae.
  2. Have close or household (i.e., share the same apartment or house) high-risk contacts including but not limited to:

    1. Persons greater than or equal to 65 years of age.
    2. Children less than or equal to 5 years of age.
    3. Residents of nursing homes.
    4. Persons of any age with significant chronic medical conditions such as:

      • Chronic pulmonary disease (e.g., asthma).
      • Chronic cardiovascular disease (e.g., cardiomyopathy, congestive heart failure, cardiac surgery, ischemic heart disease, known anatomic defects).
      • Contacts who required medical follow-up or hospitalization during the past 5 years because of chronic metabolic disease (e.g., diabetes mellitus, renal dysfunction, hemoglobinopathies).
      • Immunosuppression or cancer.
      • Neurological and neurodevelopmental conditions (e.g., cerebral palsy, epilepsy, stroke, seizures).
      • Individuals who are receiving long-term aspirin therapy.
      • Women who are pregnant or who are trying to become pregnant.
  3. Individual with body mass index (BMI) less than or equal to 18.5 and greater than or equal to 40.
  4. Smokes more than 4 cigarettes or other tobacco products on weekly basis.
  5. Complete blood count (CBC) with differential outside of the NIH DLM normal reference range and deemed clinically significant by the PI.
  6. Chemistries in the acute care, mineral, and/or hepatic panels, and/or any of the following: lactate dehydrogenase, uric acid, creatine kinase, and total protein outside of the NIH DLM normal reference range and deemed clinically significant by the PI.
  7. Neutropenia below 1,500 cells/mm(3) (Grade 2 or greater)
  8. Urinalysis outside of the NIH DLM normal reference range and deemed clinically significant by the PI.
  9. Clinically significant abnormality on electrocardiogram.
  10. Clinically significant abnormality as deemed by the PI on echocardiographic testing.
  11. Clinically significant abnormality as deemed by the PI on the Pulmonary Function Test (PFT).
  12. Recent acute illness within 1 week of admission to the isolation facility.
  13. Known allergy to treatments for influenza (including but not limited to oseltamivir, nonsteroidals).
  14. Known allergy to 2 or more classes of antibiotics (e.g., penicillins, cephalosporins, fluoroquinolones, or glycopeptides).
  15. Receipt of blood or blood products (including immunoglobulins) within 3 months prior to enrollment.
  16. Receipt of any unlicensed drug within 3 months or 5.5 half-lives (whichever is greater) prior to enrollment.
  17. Receipt of any non-influenza related unlicensed vaccine within 6 months prior to enrollment.
  18. Self-reported or known history of current alcoholism or drug abuse, or positive urine/serum test for drugs of abuse (i.e., amphetamines, cocaine, benzodiazepines, opiates, or metabolites, but not tetrahydrocannabinol (THC) or metabolites).
  19. Self-reported or known history of psychiatric or psychological issues deemed by the PI to be a contraindication to protocol participation
  20. Known close contact with anyone known to have influenza in the past 7 days.
  21. Any condition or event that, in the judgment of the PI, is a contraindication to protocol participation or impairs the volunteer s ability to give informed consent.

学习计划

本节提供研究计划的详细信息,包括研究的设计方式和研究的衡量标准。

研究是如何设计的?

设计细节

  • 主要用途:基础科学
  • 分配:非随机化
  • 介入模型:单组作业
  • 屏蔽:无(打开标签)

武器和干预

参与者组/臂
干预/治疗
实验性的:High Titer (HAI > or = 1:40)
Subjects with prechallenge hemagglutination inhibition (HAI) titers of ≥1:40 were assigned to this group. The human challenge virus, Ca/04/2009/H1N1r Challenge Virus, will be administered intranasally to each participant using a nasal sprayer. A total volume of up to 1 mL of virus will be administered.
The human challenge virus will be administered intranasally to each participant using a nasal sprayer. A total volume of up to 1 mL of virus will be administered.
实验性的:Low Titer (HAI < 1:40)
Subjects with prechallenge hemagglutination inhibition (HAI) titers of <1:40 were assigned to this group. The human challenge virus, Ca/04/2009/H1N1r Challenge Virus, will be administered intranasally to each participant using a nasal sprayer. A total volume of up to 1 mL of virus will be administered.
The human challenge virus will be administered intranasally to each participant using a nasal sprayer. A total volume of up to 1 mL of virus will be administered.

研究衡量的是什么?

主要结果指标

结果测量
措施说明
大体时间
Number of Patients With Mild to Moderate Influenza Disease (MMID)
大体时间:Within 10 days of inoculation
This was determined by presence of the combination of symptoms of influenza and presence of a positive clinical test for influenza. If both were present then the participant had positive MMID.
Within 10 days of inoculation

次要结果测量

结果测量
措施说明
大体时间
Clinical Disease Severity Score
大体时间:Within 28 days after inoculation
This was measured using a validated participant directed questionnaire called FLUPRO. This is then scored daily with a range of score from 0-185. The total score is the sum of all time points the questionnaire is given, which is 16 time points. Therefore the total score range is from 0-2960. 0 would represent no symptoms over the 16 time points while 2960 would represent maximum symptoms and perceived severity at all 16 time points.
Within 28 days after inoculation
Duration of Shedding (Days)
大体时间:Within 14 days of inoculation
The number of days total from the time a participant had the first positive test for influenza to their last positive test.
Within 14 days of inoculation
Duration of Symptoms (Days)
大体时间:within 68 days after inoculation
The number of days a participant experienced any influenza symptoms
within 68 days after inoculation
Number of Symptoms
大体时间:within 68 days after inoculation
A simple count of the number of unique influenza symptoms the participant experienced.
within 68 days after inoculation
Number of Participants With Influenza Symptoms
大体时间:within 68 days after inoculation
This was determined by the presence or absence of influenza symptoms.
within 68 days after inoculation

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

出版物和有用的链接

负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查,以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始

2013年9月1日

初级完成 (实际的)

2015年9月1日

研究完成 (实际的)

2015年9月1日

研究注册日期

首次提交

2013年10月23日

首先提交符合 QC 标准的

2013年10月23日

首次发布 (估计)

2013年10月29日

研究记录更新

最后更新发布 (实际的)

2017年4月24日

上次提交的符合 QC 标准的更新

2017年3月13日

最后验证

2017年3月1日

更多信息

与本研究相关的术语

其他研究编号

  • 130215
  • 13-I-0215 (其他标识符:United States: The National Institutes of Health)

计划个人参与者数据 (IPD)

计划共享个人参与者数据 (IPD)?

是的

IPD 计划说明

Data will be shared through the NIH data repository BTRIS - Biomedical Translational Research Information System

此信息直接从 clinicaltrials.gov 网站检索,没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求,请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改,我们的网站上也会自动更新.

订阅