Clinical trial NCT06024707: Fluctuation Analyses of Asthma Patients With Biologics Use
Official title: Early Detection of the Effectiveness of Treatment With Biologicals in Patients With Severe Asthma Using Fluctuation Analysis of Biomarkers
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Asthma
Keywords: Fluctuation Pattern
Spirometry
FeNO
Impulse oscillometry
Lead sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Sponsor class: OTHER
First posted: 2023-09-06
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with severe asthma who will start treatment with a biological from 18-60 years old.

Brief summary: 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.

Detailed description: 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.

Main study parameters/endpoints: The Respicorder device measures standard spirometry (FEV1, FVC), IOS parameters and FeNO, which will be used for fluctuation analysis. The Asthma Control Questionnaire (ACQ),Asthma Quality of Life Questionnaire (AQLQ) and Severe Asthma Questionnaire (SAQ) will be used to quantify asthma status. Patients will be evaluated by their treating clinician after 4 and 6 months of treatment with a biological. The outcome will be linked to the fluctuation patterns, such that can be evaluated whether these patterns can be used to predict a successful treatment with a biologic.

Secondary study parameters:

Spirometry, IOS and FeNO measurements with standard devices as done in standard care in the hospital will be used to compare with the Respicorder measurements. Subjects will also be asked about their experience with the Respicorder.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: The risk for adverse events due to participation in this study is minimal. The daily additional measurements with the Respicorder device can be a burden to patients. The Respicorder measurements take about 5 minutes, which we consider as an acceptable burden given the expected impact of the study. Subjects will also be subjected to measurements according to the standard protocol in clinical care.

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

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 1.
* 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

Primary outcomes:
measure: Fluctuation pattern of spirometry
timeFrame: 2-3 months
measure: Fluctuation pattern of FeNO
timeFrame: 2-3 months
measure: Fluctuation pattern of IOS
timeFrame: 2-3 months
measure: Treatment success with biological
timeFrame: at 4-6 months after start treatment with biological
measure: trend of Asthma Control Questionnaire
timeFrame: 1x a week for 2-3 months + at 4-6 months after start treatment with biological
measure: trend of Asthma Quality of Life Questionnaire
timeFrame: 1x a week for 2-3 months + at 4-6 months after start treatment with biological
measure: trend of Severe Asthma Questionnaire
timeFrame: 1x a week for 2-3 months + at 4-6 months after start treatment with biological
measure: trend of PESAM questionnaire
timeFrame: at 1+ 2 (if applicable) + 4-6 months after start treatment with biological
Secondary outcomes:
measure: FEV1 as measured with standard Spirometry
timeFrame: 3 or 4 times during 2-3 months
measure: FVC as measured with standard Spirometry
timeFrame: 3 or 4 times during 2-3 months
measure: Standard Impulse oscillometry
timeFrame: 3 or 4 times during 2-3 months
measure: standard FeNO
timeFrame: 3 or 4 times during 2-3 months
measure: lab values from standard care before study
timeFrame: At inclusion
measure: lab values from standard care during study
timeFrame: at 4-6 months after start treatment with biological
measure: Rate of medication reduction after the start of treatment with the biological
timeFrame: At inclusion
measure: Respicorder adherence (% of possible measurements actually performed)
timeFrame: 2-3 months
measure: Respicorder qualitative feedback
timeFrame: 2-3 months
Other outcomes:
measure: Demographics
timeFrame: at inclusion
measure: Height
timeFrame: at inclusion
measure: Descriptives
timeFrame: at inclusion
measure: Weight
timeFrame: at inclusion
measure: Eosinophil count thoughout study
timeFrame: at inclusion + 5-7 months from inclusion to follow up
measure: Chronic rhinosinusitis
timeFrame: At inclusion
measure: Recent vaccinations
timeFrame: At inclusion + 5-7 months from inclusion to follow up
measure: Allergies
timeFrame: at inclusion
measure: Sickness during study period
timeFrame: 5-7 months from inclusion to follow up
measure: Day/night rhytm
timeFrame: at inclusion
Locations:
Study officials:
affiliation: Amsterdam UMC, location AMC
name: Els Weersink, Dr.
role: PRINCIPAL_INVESTIGATOR
References: