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PrecISE (Precision Interventions for Severe and/or Exacerbation-Prone Asthma) Network Study

Overview

About this study

The purpose of this study is to evaluate several interventions given to participants with severe asthma. Interventions are administered in a crossover manner with 16-week treatment periods followed by 8 to 16 week washout.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • Provision of signed and dated informed consent form 
  • Started willingness to comply with all study procedures and availability for the duration of the study 
  • Male or female, age ≥ 12 years 
  • No change in asthma medications for the past 2 months and use of medium or high dose inhaled corticosteroids (ICS) (defined by Table 1A) + an additional asthma controller/biologic (defined in Tables 1B and 1C). Participants entered into the run-in on medium dose ICS will be switched to high dose ICS. They must meet all entry criteria at the time of randomization including the criteria for uncontrolled asthma as assessed by symptoms during the two weeks prior to the randomization. 
  • Baseline poor or uncontrolled asthma, defined as meeting at least one of the following: 1. FEV1 <80% predicted (for adults ≥18) or FEV1<90% (pediatric participants <18) AND with 12% bronchodilator reversibility 2. Poor symptom control - Asthma Control Questionnaire ( ACQ-6) Score ≥1.5.   

Exclusion Criteria:

  • Current participation in an interventional trial (e.g. drugs, diets, etc.) 
  • Enrollment in a clinical trial where the study medication was administered within the past 60 days or within 5 half-lives (whichever is greater) 
  • Physician diagnosis of other chronic pulmonary disorders associated with asthma-like symptoms, including, but not limited to, cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD), chronic bronchitis, emphysema, severe scoliosis or chest wall deformities that affect lung function, or congenital disorders of the lungs or airways 
  • Receiving one or more immune-modulating therapies for diseases other than asthma 
  • Receiving methotrexate, mycophenolate (CellCept®), or azathioprine (Imuran®) 
  • Receiving aero allergen immunotherapy and not on at least 3 months of maintenance allergen immunotherapy 
  • History of smoking 1. If <30 years old: Smoked for ≥5 pack-years* -Can still be enrolled if <30, smoked <5 5 pack years and none in past year, and normal (negative) urine cotinine
  • 2. If 30-39 years old: Smoked for ≥10 pack years -Can still be enrolled if ≥30, smoked <10 pack years and none in past year, provided participant demonstrates a normal (negative) urine cotinine
  • 3. If ≥40 years old: Smoked ≥15 pack years -Can still be enrolled if ≥40 years old, smoked <15 pack years and none in the last year, provided participant demonstrates normal (negative) urine cotinine. Patients with a smoking history of ≥10 to <15 pack years will also need to demonstrate a normal Diffusing Capacity for Carbon Monoxide (DLCO) (>70% predicted) * Smoking equivalent pack years. One pack of cigarettes a day for 1 year is equivalent to: 1. 1 cigar or pipe per day for 1 year 2. Smoked hookah or shisha =1 session per day for 1 year 
  • Vaped e-cigarettes =0.5 mLs e-liquid per day for 1 year, or =1 cartridge/tank/pod per day for 1 year 
  • 1 use of marijuana per day for 1 year 
  • Active use of any inhalant >1 time per month in the past year 
  • Active smoking of conventional tobacco, inhaling of marijuana or other drugs, or vaping of e-cigarettes or vape pods >1 time per month in the past year. Any form of tobacco qualifies, such as: 1 cigarette, 1 hookah or shisha sessions, 1 cigar, 1 pipe, etc. Any electronic (e)-device included: e-cigarette e-cig, mod, vape pen, JUUL vaping device, e-cigar, e-hookah, e-pipe, vape pods, etc. Any form of inhaled marijuana, including smoking marijuana leaves or inhaling THC (tetrahydrocannabinol) via e-cigarette or device

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Matthew Rank, M.D.

Closed for enrollment

Contact information:

Temeka Simmons

(480) 301-9224

Simmons.Temeka@mayo.edu

More information

Publications

  • Occurrence of severe asthma exacerbations are the cornerstone of the evaluation of asthma management, but severe asthma exacerbations are rare events. Therefore, trials that assess drug efficacy on exacerbations are done late in clinical development programmes. We aimed to establish an endpoint capturing clinically relevant deteriorations (diary events) that, when combined with severe exacerbations, create a composite outcome (CompEx). CompEx needs to strongly mirror results seen with the severe exacerbation-validated outcome, to allow the design of clinical trials of shorter duration and that include fewer patients than trials assessing severe exacerbations. Read More on PubMed
  • Phenotypic distinctions between severe asthma (SA) and nonsevere asthma (NONSA) may be confounded by differential adherence or incorrect use of corticosteroids. Read More on PubMed
  •  To determine the frequency of prescriptions for short term use of oral corticosteroids, and adverse events (sepsis, venous thromboembolism, fractures) associated with their use. Retrospective cohort study and self controlled case series. Nationwide dataset of private insurance claims. Adults aged 18 to 64 years who were continuously enrolled from 2012 to 2014. Rates of short term use of oral corticosteroids defined as less than 30 days duration. Incidence rates of adverse events in corticosteroid users and non-users. Incidence rate ratios for adverse events within 30 day and 31-90 day risk periods after drug initiation. Of 1 548 945 adults, 327 452 (21.1%) received at least one outpatient prescription for short term use of oral corticosteroids over the three year period. Use was more frequent among older patients, women, and white adults, with significant regional variation (all P<0.001). The most common indications for use were upper respiratory tract infections, spinal conditions, and allergies. Prescriptions were provided by a diverse range of specialties. Within 30 days of drug initiation, there was an increase in rates of sepsis (incidence rate ratio 5.30, 95% confidence interval 3.80 to 7.41), venous thromboembolism (3.33, 2.78 to 3.99), and fracture (1.87, 1.69 to 2.07), which diminished over the subsequent 31-90 days. The increased risk persisted at prednisone equivalent doses of less than 20 mg/day (incidence rate ratio 4.02 for sepsis, 3.61 for venous thromboembolism, and 1.83 for fracture; all P<0.001). One in five American adults in a commercially insured plan were given prescriptions for short term use of oral corticosteroids during a three year period, with an associated increased risk of adverse events. Read More on PubMed
  • The size of the placebo response in type 2 diabetes (T2DM) treatment and its relation to the route of drug administration have not been systematically reviewed. We aimed to determine weight loss, change in HbA1c and incidence of adverse events after treatment with injectable placebo GLP-1 receptor agonist (GLP-1ra), compared with oral placebo DPP-4 inhibitor (DPP-4i) and placebo SGLT-2 inhibitor (SGLT-2i). Read More on PubMed
  • In this paper, we introduce a new type of tree-based method, reinforcement learning trees (RLT), which exhibits significantly improved performance over traditional methods such as random forests (Breiman, 2001) under high-dimensional settings. The innovations are three-fold. First, the new method implements reinforcement learning at each selection of a splitting variable during the tree construction processes. By splitting on the variable that brings the greatest future improvement in later splits, rather than choosing the one with largest marginal effect from the immediate split, the constructed tree utilizes the available samples in a more efficient way. Moreover, such an approach enables linear combination cuts at little extra computational cost. Second, we propose a variable muting procedure that progressively eliminates noise variables during the construction of each individual tree. The muting procedure also takes advantage of reinforcement learning and prevents noise variables from being considered in the search for splitting rules, so that towards terminal nodes, where the sample size is small, the splitting rules are still constructed from only strong variables. Last, we investigate asymptotic properties of the proposed method under basic assumptions and discuss rationale in general settings. Read More on PubMed
  • The placebo effect is a complex phenomenon occurring across a variety of clinical conditions. While much placebo research has been conducted in diseases defined by self-report such as depression, chronic pain, and irritable bowel syndrome (IBS), asthma has been proposed as a useful model because of its easily measured objective outcomes. Studies examining the placebo response in asthma have not only contributed to an understanding of the mechanisms behind the placebo response but also shed an interesting light on the current treatment and diagnosis of asthma. This paper will review current literature on placebos in general and specifically on the placebo response in asthma. It focuses on what we know about the mechanisms behind the placebo effect, whether there is a specific portion of the population who responds to placebos, which patient outcomes are influenced by the placebo effect, and whether the effect can be augmented. Read More on PubMed
  • There is increasing interest in discovering individualized treatment rules for patients who have heterogeneous responses to treatment. In particular, one aims to find an optimal individualized treatment rule which is a deterministic function of patient specific characteristics maximizing expected clinical outcome. In this paper, we first show that estimating such an optimal treatment rule is equivalent to a classification problem where each subject is weighted proportional to his or her clinical outcome. We then propose an outcome weighted learning approach based on the support vector machine framework. We show that the resulting estimator of the treatment rule is consistent. We further obtain a finite sample bound for the difference between the expected outcome using the estimated individualized treatment rule and that of the optimal treatment rule. The performance of the proposed approach is demonstrated via simulation studies and an analysis of chronic depression data. Read More on PubMed
  • Long-acting beta-agonist (LABA) therapy improves symptoms in patients whose asthma is poorly controlled by an inhaled glucocorticoid alone. Alternative treatments for adults with uncontrolled asthma are needed. Read More on PubMed
  • For children who have uncontrolled asthma despite the use of low-dose inhaled corticosteroids (ICS), evidence to guide step-up therapy is lacking. Read More on PubMed
  • The Severe Asthma Research Program cohort includes subjects with persistent asthma who have undergone detailed phenotypic characterization. Previous univariate methods compared features of mild, moderate, and severe asthma. Read More on PubMed
  • Information that enhances expectations about drug effectiveness improves the response to placebos for pain. Although asthma symptoms often improve with placebo, it is not known whether the response to placebo or active treatment can be augmented by increasing expectation of benefit. Read More on PubMed
  • More evidence is needed on which to base recommendations for treatment of mild-moderate persistent asthma in school-aged children. Read More on PubMed
  • In adaptive treatment strategies, the treatment level and type is repeatedly adjusted according to ongoing individual response. Since past treatment may have delayed effects, the development of these treatment strategies is challenging. This paper advocates the use of sequential multiple assignment randomized trials in the development of adaptive treatment strategies. Both a simple ad hoc method for ascertaining sample sizes and simple analysis methods are provided. Read More on PubMed
  • The construct validity of a quantitative work productivity and activity impairment (WPAI) measure of health outcomes was tested for use in clinical trials, along with its reproducibility when administered by 2 different methods. 106 employed individuals affected by a health problem were randomised to receive either 2 self-administered questionnaires (self administration) or one self-administered questionnaire followed by a telephone interview (interviewer administration). Construct validity of the WPAI measures of time missed from work, impairment of work and regular activities due to overall health and symptoms, were assessed relative to measures of general health perceptions, role (physical), role (emotional), pain, symptom severity and global measures of work and interference with regular activity. Multivariate linear regression models were used to explain the variance in work productivity and regular activity by validation measures. Data generated by interviewer-administration of the WPAI had higher construct validity and fewer omissions than that obtained by self-administration of the instrument. All measures of work productivity and activity impairment were positively correlated with measures which had proven construct validity. These validation measures explained 54 to 64% of variance (p less than 0.0001) in productivity and activity impairment variables of the WPAI. Overall work productivity (health and symptom) was significantly related to general health perceptions and the global measures of interference with regular activity. The self-administered questionnaire had adequate reproducibility but less construct validity than interviewer administration. Both administration methods of the WPAI warrant further evaluation as a measure of morbidity. Read More on PubMed

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