AzTrials
AzTrials

AsthmaANASTHMANCT02836691

Autonomic Nervous System Role in Uncontrolled ASTHMA and the Paucigranulocitic Phenotype

A study testing EKG (electrocardiogram) in people with Asthma, run by Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau at 1 site in Spain.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The autonomic nervous system (ANS) plays an important role in asthma, primarily through the parasympathetic (by the cholinergic pathway) promoting bronchoconstriction. Asthma is a chronic inflammatory disease, however, bronchoconstriction is not always caused by bronchial inflammation, as occurs in paucigranulocitic… Read more about this study

Who is it for?
Ages 16 to 70 yearsHealthy volunteers can take part
Conditions the study is for
Asthma
What is being tested?
EKG (electrocardiogram)
Type of treatment
Medical device
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
1 siteSpain
Study dates
May 2016to 26 Jun 2019
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 16 to 70 years
  • All sexes
  • Healthy volunteers accepted
  • Child, Adult, Older adult

Who may be able to join

  • Patients of both sexes aged over 16 diagnosed with asthma (according to criteria GEMA 4.0). The diagnosis of asthma is assumed when the patient records stating suggestive previous symptoms of asthma with variable airflow obstruction (determined by spirometry or meter peak flow) or positive bronchodilator test (increase of 12% and 200 ml. of FEV1 after inhalation of a bronchodilator) or positive test to unspecific bronchoconstriction.

Who cannot join

  • Asthma exacerbations a month before the visit
  • Concomitance of other chronic respiratory diseases (bronchiectasis, fibrosis, etc.)
  • Other important comorbidities in the opinion of investigators example: cardiovascular, endocrinological (especially diabetes, mental retardation, psychiatric or neurological disease relevant systemic inflammatory or immune disease

Trial locations and contacts

1 site in 1 country.

Spain1 site
  • Lorena Soto-Retes

    Barcelona, 08025

Other trials in Spain

About this study

The autonomic nervous system (ANS) plays an important role in asthma, primarily through the parasympathetic (by the cholinergic pathway) promoting bronchoconstriction. Asthma is a chronic inflammatory disease, however, bronchoconstriction is not always caused by bronchial inflammation, as occurs in paucigranulocitic phenotype or noninflammatory asthma. The hypothesis of this project is based on the activation of the parasympathetic nervous system (PNS) would be involved in the pathogenesis of noninflammatory asthma (paucigranulocitic phenotype) and emotional stress and poor control of patients with severe asthma. To determine the ANS involvement in the pathogenesis of paucigranulocItic phenotype in asthma and correlate emotional stress, mediated by the ANS, with uncontrolled severe asthma. 30 asthmatics with different clinical severity (mild, severe controlled and uncontrolled severe) will be recruited , along with a control group of 10 healthy people. Descriptive variables, spirometry, inflammatory parameters (FeNO and inflammatory cell count in induced sputum), blood, saliva, urine and hair to obtain stress markers (glucose, copeptin, prolactin, cortisol) will be collected, and be supplied validated questionnaires of asthma control, quality of life and stress. For monitoring the response of the ANS will be done through an electrocardiogram, recording the heart rate variability (HRV). This analysis is carried out with the collaboration of engineers specialized in the characterization of cardiovascular signals for measuring the ANS.

Read the detailed description
  1. Role of the ANS in asthma For decades it's considered that the autonomic nervous system (ANS) plays an important role in the pathophysiology and symptomatology of asthma. The ANS had important functions besides regulating airway, such as bronchial smooth muscle tone, secretions, blood flow, microvascular permeability, also acts on migration and release of inflammatory mediators. This complex interaction between inflammation and neuronal control of airway, with effects on inflammatory mediators in neurotransmitters, modulates the inflammatory response (hypersecretion, edema and release of pro-inflammatory mediators as mast cell), through the activation of cholinergic reflex. Cholinergic neuronal pathway has a dominant effect on bronchoconstriction, and therefore represents an excellent therapeutic target. Anticholinergics reduce bronchial hyperresponsiveness to a wide range of bronchoconstriction agents, such as prostanoids, histamine, bradykinin, capsaicin, exercise or allergens.
  2. ANS and non-inflammatory asthma (paucigranulocitic) In asthma can distinguish different inflammatory phenotypes, commonly typified by the presence of eosinophil's or neutrophils, and that can be performed through non invasive techniques of inflammometric such as exhaled nitric oxide and induced sputum. But it's not always bronchoconstriction mediated by bronchial inflammation. There is a significant proportion of patients with asthma, about 40% in those not objective bronchial inflammation, to that asthma is called noninflammatory asthma or paucigranulocitic phenotype, to proceed with normal levels of eosinophil's and neutrophils in sputum. The pathogenesis of the phenotype is not well defined, although suspected to be caused by strictly mechanical mechanisms diameter of the airway induced nervous stimulation. Among these mechanisms, the PNS could play an important role, however there are no studies that have evaluated the activation of the PNS in different clinical inflammatory disease phenotypes.
  3. Control of asthma and stress Emotional stress affects the appearance and development of asthma by acting directly on the pathogenic mechanisms of airways, since states of great psychological stress have been associated with impaired adrenal sympathetic system and adrenal-pituitary-hypothalamic axis (APH). The argument that psychological stress influences the autonomic control of the airways is based primarily on the fact that many of the same autonomous mechanisms seem to play a role in asthma are involved in the activation and regulation of the physiological response to stress as chronic stress can alter the APH axis, cortisol secretion which is attenuated, leading to an increase in secretion of inflammatory cytokines.
  4. Non-Invasive methods to measure the role of ANS Some author's suggest that the altered autonomic control of the caliber of airway in asthma can be reflected through a parallel change in heart rate (HR), as it is shown that in the asthmatic population are more likely to elevated resting heart rate compared to asthmatic population. Asthma and allergy has been associated with an increased activity of the PNS and asthma causes an elevation of heart rate variability (HRV), based on the measurement of basal parasympathetic tone. In fact, the authors asthma severity associated with greater impairment of HRV.

Therefore, evaluation of ANS is of great interest for diagnosis, prognosis and monitoring of this respiratory disorder. Direct evaluation of the PNS is infeasible or impractical in these situations. However, non-invasive evaluation of the PNS is proposed through the HRV according to the standards of measurement, physiological interpretation and clinical use of guides working group of the European Society and American Cardiology and Electrophysiology that are made through the electrocardiogram (ECG).

Ultimately, this research project aims to evaluate in a comprehensive manner the role it can play the ANS in the pathogenesis of asthma, namely the uncontrolled and non-inflammatory asthma severe asthma. The results of this study could provide new clues to understand why other mechanisms of asthma that do not pass through inflammatory. And therefore identification or further characterization of the role of ANS in the disease could generate preliminary evidence on which lay further research aimed at developing new molecules with anticholinergic capacity to treat asthma.

Conditions
Asthma
Being tested
EKG (electrocardiogram)
Keywords
Autonomic nervous system, Uncontrolled severe asthma, Paucigranulocitic asthma phenotype, Stress
Medical subject headings
Asthma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EKG (electrocardiogram)Device

    Analysis of the heart rate variability with an electrocardiogram with a commercial device adapted to asthmatic patients using 12 leads, a respiratory band and a pulseoximeter.

Study groups in NCT02836691
Study groupRoleWhat they receive
EKG to Control subjectsActive comparatorhealthy controls without asthma or other respiratory disease.
Receives: Device: EKG (electrocardiogram)
EKG monitoring Mild asthmaActive comparatorThe clinical grade of asthma is assessed in terms of the type of current asthma control (as GEMA Guide 4.0)
Receives: Device: EKG (electrocardiogram)
EKG monitoring severe control asthmaActive comparatorThe clinical grade of asthma is assessed in terms of the type of current asthma control (as GEMA Guide 4.0)
Receives: Device: EKG (electrocardiogram)
EKG monitoring severe uncontrolled asthmaActive comparatorThe clinical grade of asthma is assessed in terms of the type of current asthma control (as GEMA Guide 4.0)
Receives: Device: EKG (electrocardiogram)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Heart rate variability (HRV)

    Comparison of heart rate variability (HRV) through an EKG among the group of non-inflammatory asthma (paucigranulocitic) with the rest of inflammatory phenotypes of severe asthma analyzed.

    Measured: 2 years

Secondary outcomes (7)
  1. Stress

    Stress will be evaluated with validated questionnaires. Hospital Anxiety and Depression Scale (HADS)

    Measured: 2 years

  2. Glucose (mg/dL)

    Blood determination of glucose (mg/dl) as biomarker of emotional stress in patients with severe uncontrolled asthma.

    Measured: 2 years

  3. copeptin (pmol/L)

    Blood determination of copeptin (pmol/L) as biomarker of emotional stress in patients with severe uncontrolled asthma.

    Measured: 2 years

  4. Prolactin (ng/mL)

    Blood determination of prolactin (ng/mL) as biomarker of emotional stress in patients with severe uncontrolled asthma.

    Measured: 2 years

  5. Salivary cortisol (ng/ml)

    Salivary determination of cortisol (ng/ml) as biomarker of emotional stress in patients with severe uncontrolled asthma.

    Measured: 2 years

  6. Salivary alpha-amylase U/L

    Salivary determination of alpha-amylase U/L as biomarker of emotional stress in patients with severe uncontrolled asthma.

    Measured: 2 years

  7. Urine cortisol (mcg/24h)

    Urine cortisol (mcg/24h) as biomarker of emotional stress in patients with severe uncontrolled asthma.

    Measured: 24 hours

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Jul 2016 (estimated)
  2. Study startMay 2016
  3. Primary completionMar 2017
  4. Study completion26 Jun 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Basic science
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
40 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02836691
Sponsor's protocol ID
IIBSP-SNA-2015-87
Acronym
ANASTHMA
Status last verified
Feb 2020
First submitted
5 May 2016
Last updated
17 Feb 2020
Results posted
No
Data monitoring committee
No
Individual data sharing
No

Publications

  • Kaliner M, Shelhamer JH, Davis PB, Smith LJ, Venter JC. Autonomic nervous system abnormalities and allergy. Ann Intern Med. 1982 Mar;96(3):349-57. doi: 10.7326/0003-4819-96-3-349.

    PubMed 6277221
  • Barnes PJ. Neuroeffector mechanisms: the interface between inflammation and neuronal responses. J Allergy Clin Immunol. 1996 Nov;98(5 Pt 2):S73-81; discussion S81-3.

    PubMed 8939180
  • Gosens R, Bos IS, Zaagsma J, Meurs H. Protective effects of tiotropium bromide in the progression of airway smooth muscle remodeling. Am J Respir Crit Care Med. 2005 May 15;171(10):1096-102. doi: 10.1164/rccm.200409-1249OC. Epub 2005 Feb 1.

    PubMed 15695490
  • Peters SP, Kunselman SJ, Icitovic N, Moore WC, Pascual R, Ameredes BT, Boushey HA, Calhoun WJ, Castro M, Cherniack RM, Craig T, Denlinger L, Engle LL, DiMango EA, Fahy JV, Israel E, Jarjour N, Kazani SD, Kraft M, Lazarus SC, Lemanske RF Jr, Lugogo N, Martin RJ, Meyers DA, Ramsdell J, Sorkness CA, Sutherland ER, Szefler SJ, Wasserman SI, Walter MJ, Wechsler ME, Chinchilli VM, Bleecker ER; National Heart, Lung, and Blood Institute Asthma Clinical Research Network. Tiotropium bromide step-up therapy for adults with uncontrolled asthma. N Engl J Med. 2010 Oct 28;363(18):1715-26. doi: 10.1056/NEJMoa1008770. Epub 2010 Sep 19.

    PubMed 20979471
  • Malerba M, Ragnoli B, Radaeli A, Tantucci C. Usefulness of exhaled nitric oxide and sputum eosinophils in the long-term control of eosinophilic asthma. Chest. 2008 Oct;134(4):733-739. doi: 10.1378/chest.08-0763.

    PubMed 18842911
  • Schleich FN, Manise M, Sele J, Henket M, Seidel L, Louis R. Distribution of sputum cellular phenotype in a large asthma cohort: predicting factors for eosinophilic vs neutrophilic inflammation. BMC Pulm Med. 2013 Feb 26;13:11. doi: 10.1186/1471-2466-13-11.

    PubMed 23442497
  • Douwes J, Gibson P, Pekkanen J, Pearce N. Non-eosinophilic asthma: importance and possible mechanisms. Thorax. 2002 Jul;57(7):643-8. doi: 10.1136/thorax.57.7.643.

    PubMed 12096210
  • Wright RJ. Exploring biopsychosocial influences on asthma expression in both the family and community context. Am J Respir Crit Care Med. 2008 Jan 15;177(2):129-30. doi: 10.1164/rccm.200710-1526ED. No abstract available.

    PubMed 18165380
  • Haldar P, Pavord ID. Noneosinophilic asthma: a distinct clinical and pathologic phenotype. J Allergy Clin Immunol. 2007 May;119(5):1043-52; quiz 1053-4. doi: 10.1016/j.jaci.2007.02.042.

    PubMed 17472810
  • Lehrer PM, Isenberg S, Hochron SM. Asthma and emotion: a review. J Asthma. 1993;30(1):5-21. doi: 10.3109/02770909309066375.

    PubMed 8428858
  • Wright RJ, Rodriguez M, Cohen S. Review of psychosocial stress and asthma: an integrated biopsychosocial approach. Thorax. 1998 Dec;53(12):1066-74. doi: 10.1136/thx.53.12.1066.

    PubMed 10195081
  • Kallenbach JM, Webster T, Dowdeswell R, Reinach SG, Millar RN, Zwi S. Reflex heart rate control in asthma. Evidence of parasympathetic overactivity. Chest. 1985 May;87(5):644-8. doi: 10.1378/chest.87.5.644.

    PubMed 3987376
  • Shah PK, Lakhotia M, Mehta S, Jain SK, Gupta GL. Clinical dysautonomia in patients with bronchial asthma. Study with seven autonomic function tests. Chest. 1990 Dec;98(6):1408-13. doi: 10.1378/chest.98.6.1408.

    PubMed 2245682
  • Garrard CS, Seidler A, McKibben A, McAlpine LE, Gordon D. Spectral analysis of heart rate variability in bronchial asthma. Clin Auton Res. 1992 Apr;2(2):105-11. doi: 10.1007/BF01819665.

    PubMed 1638105
  • Tokuyama K, Morikawa A, Mitsuhashi M, Mochizuki H, Tajima K, Kuroume T. Beat-to-beat variation of the heart rate in children with allergic asthma. J Asthma. 1985;22(6):285-8. doi: 10.3109/02770908509087111.

    PubMed 4077809

Questions about this trial

What is this clinical trial studying?

A study testing EKG (electrocardiogram) in people with Asthma, run by Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau at 1 site in Spain.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 1 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 17 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Heart rate variability (HRV) (time frame: 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02836691, which also lists 16 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Feb 2020.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in