Early Detection of the Effectiveness of Treatment With Biologicals in Patients With Severe Asthma Using Fluctuation Analysis of Biomarkers
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 48
- 主要终点
- trend of PESAM questionnaire
研究概览
简要总结
The goal of this observational study is to compare the fluctuation patterns of biomarkers (Spirometry, FeNO, IOS) of responders and non-responders in asthma patients who will start treatment with a biologic. The main question it aims to answer is: Can fluctuation patterns of parameters for spirometry, FeNO and IOS before and after starting treatment with biologics in patients with severe asthma be used to predict a successful intervention.
Participants will measure Spirometry, FeNO and IOS twice a day at home for 2 or 3 months starting one month before starting treatment with a biological.
详细描述
SUMMARY
Rationale: Treatment of patients with severe asthma has taken a new avenue with the introduction of biologics. Currently, treatment success with biologics may be around 75% and is determined by assessing various biomarkers after 4 to 6 months of treatment. At a stable state, biological processes dynamically fluctuate within certain borders, which differ between asthma and healthy controls. By exposure to the common cold virus, we have shown that destabilizing the condition of asthma patients and healthy controls directly but temporarily changes the fluctuation patterns of biological processes. We propose that treatment success also changes fluctuation patterns, and that this occurs relatively fast after treatment is started. By daily measurements of spirometry, fraction of exhaled nitric oxide (FeNO) and impulse oscillometry (IOS), using the Respicorder device, we expect to determine the effect of treatment at an early stage and limit prolonged treatment of patients with a non-effective biologic, and the very high costs of these biologics.
Objective: To investigate the fluctuation patterns of different pulmonary parameters in patients with severe asthma, before and after starting a treatment with biologics, using daily measurements with the Respicorder device.
Study design: The study design is an observational cohort study that will include patients that are scheduled for an intervention with biologic treatment in standard care. Patients will receive their standard treatment and will perform some extra measurements during their regular visits and they will perform measurements with the Respicorder device twice a day at home.
Study population: 48 patients with severe asthma between 18-60 years old who will start treatment with biologics.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •In order to be eligible to participate in this study, a subject must meet all of the following criteria:
- •Severe asthma based on the definition by the 2022 GINA guidelines.
- •Will start treatment with a biological
- •18-60 years old
- •Subject should be willing and able to perform the lung function tests and other study-related procedures and comply with study protocol requirements.
- •Apart from their asthma, subjects should be generally healthy with no history of a clinically relevant medical condition that in the opinion of the investigator might interfere with successful study conduct and no clinically relevant abnormalities on medical history.
- •Subjects should provide a signed and dated informed consent
排除标准
- •A potential subject who meets any of the following criteria will be excluded from participation in this study:
- •Has been tested positively for COVID-19 in the past month or has not fully recovered from an earlier COVID-19 infection (e.g. post-covid syndrome)
- •Has been treated with oral corticosteroids as high-dose therapy in the 6 weeks before visit
- •Has been treated with another biologic within 3 months before start treatment with new biological (e.g. 2 months before the start of the study participation)
- •Not able to perform spirometry/IOS/FeNO tests correctly
- •Not able to handle Respicorder well
- •Subject is a current smoker/vaper, uses recreational drugs, or has >10 packyears
- •Subject is anticipated not to comply with study protocol or other aspects of the study (at the discretion of the investigator)
- •Participation to the study is not medically responsible according to the study physician and/or principle investigator
- •Inability to read and/or understand the Dutch language
研究组 & 干预措施
Asthma patients
All asthma patients will be observed and receive their regular treatment
干预措施: Biological Drug (Drug)
结局指标
主要结局
trend of PESAM questionnaire
时间窗: at 1+ 2 (if applicable) + 4-6 months after start treatment with biological
Patient Experience and SAtisfaction with Medication (PESAM) represents patients satisfaction with the treatment with the biological
Fluctuation pattern of spirometry
时间窗: 2-3 months
Subjects will perform spirometry measurements 2x a day. This data will be used to create a fluctuation pattern of the FEV1(L) and FVC (L). The change in fluctuation pattern before and after start of treatment will be compared between responders and non-responders to treatment with a biological. The fluctuation pattern cannot be described as one parameter, but is a combination of several properties (phase-space plot, entropy). This study has an explorative nature that will aim to assess how such a fluctuation pattern can be described.
Fluctuation pattern of FeNO
时间窗: 2-3 months
Subjects will perform FeNO measurements 2x a day. This data will be used to create a fluctuation pattern of FeNO (ppb). The change in fluctuation pattern before and after start of treatment will be compared between responders and non-responders to treatment with a biological. The fluctuation pattern cannot be described as one parameter, but is a combination of several properties (phase-space plot, entropy). This study has an explorative nature that will aim to assess how such a fluctuation pattern can be described.
Fluctuation pattern of IOS
时间窗: 2-3 months
Subjects will perform impulse oscillometry (IOS) measurements 2x a day. This data will be used to create a fluctuation pattern of the IOS parameters (R5, R20, X5, Fs, AX etc). The change in fluctuation pattern before and after start of treatment will be compared between responders and non-responders to treatment with a biological. The fluctuation pattern cannot be described as one parameter, but is a combination of several properties and parameters (phase-space plot, entropy). This study has an explorative nature that will aim to assess how such a fluctuation pattern can be described.
Treatment success with biological
时间窗: at 4-6 months after start treatment with biological
Treatment success is defined if two or more of the following are true: * A decrease of ACQ score of 0,5 points or an ACQ≤1,5 after 4-6 months compared to visit 2 (start of treatment with biological) and/or * An increase of SAQ score of 0,5 points after 4-6 months compared to visit 2 (start of treatment with biological) and/or * Minimal 30% reduction of dose of maintenance treatment with OCS after 4-6 months compared to visit 2 (start of treatment with biological) * and/or Decrease in exacerbation rate in the 4-6 months after visit 2 compared to the same period (4-6 months) before visit 2
trend of Asthma Control Questionnaire
时间窗: 1x a week for 2-3 months + at 4-6 months after start treatment with biological
average of 7 questions regarding asthma control (scorerange 0-6), higher score means worse asthma control
trend of Asthma Quality of Life Questionnaire
时间窗: 1x a week for 2-3 months + at 4-6 months after start treatment with biological
average of 32 questions regarding impact of asthma on quality of life (scorerange 1-7), higher score means better quality of life
trend of Severe Asthma Questionnaire
时间窗: 1x a week for 2-3 months + at 4-6 months after start treatment with biological
SAQ-score: average of 16 questions regarding severe asthma (scorerange 1-7), higher score means better quality of life. SAQ-global: score representing overall satisfaction (scorerange 0-100)
次要结局
- FVC as measured with standard Spirometry(3 or 4 times during 2-3 months)
- FEV1 as measured with standard Spirometry(3 or 4 times during 2-3 months)
- Standard Impulse oscillometry(3 or 4 times during 2-3 months)
- standard FeNO(3 or 4 times during 2-3 months)
- lab values from standard care before study(At inclusion)
- lab values from standard care during study(at 4-6 months after start treatment with biological)
- Rate of medication reduction after the start of treatment with the biological(At inclusion)
- Respicorder adherence (% of possible measurements actually performed)(2-3 months)
- Respicorder qualitative feedback(2-3 months)
研究者
Els J.M. Weersink
Pulmonary Physician
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)