Clinical trial NCT04340583: Subjective Sleep Quality and Sleep Disorders in Patients With Severe Asthma
Official title: Subjective Sleep Quality and Prevalence of Sleep Disorders in Patients With Severe Asthma
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Asthma
Keywords: Sleep disorder
Monoclonal therapy
Anxiety
Depression
Lead sponsor: Istituti Clinici Scientifici Maugeri SpA
Sponsor class: OTHER
First posted: 2020-04-09
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients referral to medical clinic

Brief summary: Bronchial asthma is characterized by the presence of symptoms that vary over time and of severity. Asthma symptoms tend to worsen at night and in the early hours of the morning, and the presence of nocturnal symptoms is an important indicator of therapeutic intervention in order to control the severity of the disease. Aim of the study is to investigate sleep disorders and quality, as well as and depressive and anxiety symptoms in patients affected by severe asthma before and after 6 months of treatment with monoclonal therapy. An observational, cohort, prospective, monocentric study will be conducted to evaluate subjective quality of sleep at baseline and post monoclonal treatment.

Detailed description: Rationale

Bronchial asthma is a heterogeneous and highly prevalent disease; moreover, it represents one of the main cost of the Italian National Health Care System. According to international guidelines, asthma is characterized by the presence of symptoms such as wheezing, dyspnoea, chest tightness and / or cough, and limitation of expiratory air flow, that vary over time and of severity.

The main therapy consists of the use of inhaled corticosteroids in order to reduce airway inflammation; however, in conditions characterized by frequent exacerbations, patients take oral corticosteroids (OCS) cyclically or chronically to control their symptoms. Asthma symptoms tend to worsen at night and in the early hours of the morning, and the presence of nocturnal symptoms is an important indicator of therapeutic intervention in order to control the severity of the disease.

Several studies have shown that nocturnal symptoms, such as cough and dyspnoea, are associated with circadian oscillations of airway inflammation and physiological variables, with consequent air flow limitation of and bronchial hyperreactivity. Moreover, it is known that patients receiving OCS are subjected to significant alterations of the hypothalamic-pituitary-adrenergic axis function, therefore the assumption of these drugs could cause a modification of the circadian rhythm.

Since sleep fragmentation that accompanies the worsening of nocturnal asthmatic symptoms is probably caused by the degree of severity of nocturnal bronchoconstriction, it is possible that severe asthmatic patients have greater bronchoconstriction and therefore more disturbed sleep.

Subjects with severe asthma, the 5-10% of the total asthmatic population, report symptoms that persist despite inhalation therapy, and have many exacerbations, Emergency Room access or hospitalizations.

These patients use systemic steroids at least twice a year due to asthmatic exacerbations and / or continuous therapy with systemic steroids for at least 6 consecutive months, with the development of side effects such as high blood pressure, overweight, meta-steroid diabetes and osteoporosis.

In the last ten years, the availability of alternative therapies such as monoclonal antibodies, which block the inflammatory cascade at different levels (Anti Immunoglobulin E, Anti interleukin-5 (II-5)e anti receptor Il-5) has allowed to reduce the dosage of steroid therapy up to its complete suspension.

Obstructive Sleep Apnoea (OSA) is one of the most common asthma comorbidities, especially severe, affecting about 26% of patients. When evaluated with polysomnography, the prevalence of OSA is equal to 88% in patients with severe asthma and 58% in those with moderate asthma.

It seems that OSA could contribute to asthma exacerbations, to diurnal and nocturnal symptoms and to the scarce quality of life; it also seems to modulate airway inflammation and remodeling. Asthmatic patients with OSA show a greater decline in Forced Expiratory Volume in the first second (FEV1) over time than non-OSA, and Continuous Positive Airways Pressure (CPAP) treatment seems to slow down this deterioration. Serrano Pariente et al. have demonstrated that 6 months CPAP treatment improves the outcomes of Asthma in patients with moderate OSA. Finally, a recent study has shown that patients with poorly controlled asthma tend to have worse sleep quality and greater diurnal sleepiness. The same study has demonstrated a higher prevalence of depressive symptoms in female patients with poorly controlled asthma.

Aim of the study is to investigate sleep disorders and quality, as well as and depressive and anxiety symptoms in patients affected by severe asthma before and after 6 months of treatment with monoclonal therapy.

Primary outcome is to evaluate subjective quality of sleep at baseline and post treatment.

Secondary outcomes are: to verify pre and post treatment: the presence of insomnia, respiratory disorders, circadian rhythm disorders, diurnal sleepiness or anxiety and depression symptoms.

Inclusion criteria:

* Diagnosis of severe persistent asthma
* Systemic steroids treatment for at least 6 months and/or ≥2 exacerbations in the last year
* Need to initiate monoclonal antibody therapy according to guidelines
* Age ≥18 years
* Signed Informed consent
* Patients able to collaborate in the required procedures

Exclusion criteria:

Diagnosis of cognitive impairment Study Design An observational, cohort, prospective, monocentric study will be conducted. Patients will be enrolled c/o the Pneumology Division of the Clinical and Scientific Institute Maugeri of Tradate.

Data will be collected at baseline (T0) and after 6 months of therapy with one monoclonal antibody (omalizumab, mepolizumab or benralizumab) (T6).

Eligibility criteria: Inclusion Criteria:

* Diagnosis of severe persistent asthma
* Systemic steroids treatment for at least 6 months and/or ≥2 exacerbations in the last year
* Need to initiate monoclonal antibody therapy according to guidelines
* Age ≥18 years
* Signed Informed consent
* Patients able to collaborate in the required procedures

Exclusion Criteria:

* Diagnosis of cognitive impairment

Primary outcomes:
measure: subjective quality of sleep
timeFrame: 6 months
Secondary outcomes:
measure: Insomnia
timeFrame: 6 months
measure: respiratory disorders
timeFrame: 6 months
measure: circadian rhythm disorders
timeFrame: 6 months
measure: diurnal sleepiness
timeFrame: 6 months
measure: anxiety
timeFrame: 6 months
measure: depression
timeFrame: 6 months
measure: sleep quality
timeFrame: 6 months
Other outcomes:
Locations:
city: Tradate
country: Italy
facility: Istituti Clinici Maugeri Pneumologia
state: Lombardia
Study officials:
affiliation: Istituti Clinici Maugeri
name: Antonio Spanevello, Prof
role: STUDY_CHAIR
References:
citation: Collomp R, Labsy Z, Zorgati H, Prieur F, Cottin F, Do MC, Gagey O, Lasne F, Collomp K. Therapeutic glucocorticoid administration alters the diurnal pattern of dehydroepiandrosterone. Endocrine. 2014 Aug;46(3):668-71. doi: 10.1007/s12020-013-0122-9. Epub 2013 Dec 18.
citation: Bel EH, Wenzel SE, Thompson PJ, Prazma CM, Keene ON, Yancey SW, Ortega HG, Pavord ID; SIRIUS Investigators. Oral glucocorticoid-sparing effect of mepolizumab in eosinophilic asthma. N Engl J Med. 2014 Sep 25;371(13):1189-97. doi: 10.1056/NEJMoa1403291. Epub 2014 Sep 8.
citation: Campos FL, de Bruin PFC, Pinto TF, da Silva FGC, Pereira EDB, de Bruin VMS. Depressive symptoms, quality of sleep, and disease control in women with asthma. Sleep Breath. 2017 May;21(2):361-367. doi: 10.1007/s11325-016-1422-0. Epub 2016 Oct 29.