Defining and Treating Depression-related Asthma

NCT ID: NCT04617015

Last Updated: 2023-12-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-09-09
• Study Completion Date: 2019-03-11

Brief Summary

Depression is seen more often in people with asthma, and may lead to increased development and severity of asthma.

This study will investigate whether children with depression and asthma have less allergic disease and less inflammation than children with asthma who do not have symptoms of depression.

The study will also investigate whether the lungs of children with depression and asthma respond to an anticholinergic inhaler called ipratropium more than the lungs of non-depressed asthmatic children.

Detailed Description

It is well accepted that asthma is not a single uniform disease, but rather many different disease sub-entities with different etiologies and pathophysiologies. The term "endotype" was coined to delineate distinct subtypes of asthma; an "endotype" specifically is as "a subtype of a condition, which is defined by a distinct functional or pathophysiological mechanism". The division of asthma into endotypes is critical to the development of targeted immunomodulators and other specific treatment modalities to more effectively treat the diverse asthmatics encountered in clinical practice.

There is a clear association between depression and asthma, with evidence suggesting that depression leads to increased development of asthma rather than the reverse. If, as suggested, depression truly mediates a subset of asthma, this depression-related asthma "endotype" has not been well characterized to date. A promising theory of the pathophysiological mechanism of depression-related asthma is that of autonomic nervous system dysregulation associated with depression leading to airway compromise (Miller and Wood, 2003). Specifically, depression is associated with excess parasympathetic (cholinergic) activation, and cholinergic activation can mediate bronchoconstriction through the action of acetylcholine on the muscarinic receptors on bronchial smooth muscle. It has been demonstrated that during emotional stimuli, depressed children with asthma have increased parasympathetic activation, which associates with increased airway resistance. In contrast, when experiencing these same emotional stimuli, non-depressed children with asthma have increased sympathetic activation.

The investigators anticipate that depressed child asthmatics have cholinergically-mediated bronchoconstriction as a major mediator of their disease activity. Based upon studies of depressed asthmatic children showing increased parasympathetic/cholinergic reactivity in response to laboratory based emotional stimuli, along with a recent study showing that depressed asthmatic adults have decreased bronchodilatory response to beta-agonists, the investigators hypothesize that asthmatic children with higher depressive indices will have more bronchodilatory response on spirometry following treatment with a short-acting inhaled anticholinergic, and less additional bronchodilation with an inhaled beta-agonist, compared to children with lower depressive indices. The investigators will set out to demonstrate if during an episode of bronchoconstriction, depressed child asthmatics will achieve more bronchodilation from a short-acting inhaled anticholinergic than will non-depressed child asthmatics.

The investigators next predict that with excess cholinergic activation as a cause of bronchoconstriction in depressed pediatric asthmatics, there will be less atopic sensitization and Th2-mediated inflammation driving the airway disease in this subset of asthmatics. The investigators hypothesize that, compared to non-depressed child asthmatics, depressed pediatric asthmatics during an episode of bronchoconstriction will show less evidence of airway inflammation as measured by fractional exhaled nitric oxide (FeNO) and peripheral blood eosinophilia, and will have lower rates of atopic sensitization measured by skin prick testing to environmental allergens and/or elevated total serum immunoglobulin E (IgE). In addition, the investigators will assess patient-identified asthma triggers, which are anticipated to be different in the depressed asthmatic group, with increased identification of emotions and cold weather as triggers, and less identification of allergens as triggers.

Conditions

Asthma; Depression; Childhood Asthma

Keywords

asthma; depression; anticholinergic therapy

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

Ipratropium bromide

All subjects will receive ipratropium bromide HFA and will have spirometry performed before and after ipratropium.

Group Type: EXPERIMENTAL

Ipratropium Bromide

Intervention Type: DRUG

All subjects receive inhaled ipratropium once with measurement of spirometry before and after. Bronchodilator response of subjects with depression is compare to that of subjects without depression.

Interventions

Ipratropium Bromide

All subjects receive inhaled ipratropium once with measurement of spirometry before and after. Bronchodilator response of subjects with depression is compare to that of subjects without depression.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Diagnosis of asthma
• Decreased lung volumes for age/height/race (FEV1 80% predicted or FEV1/FVC 85%) on day of study visit assessed by spirometry.

Exclusion Criteria

• Severely developmentally delayed patients, or those who suffer from other severe cognitive impairment not allowing them to perform spirometry or participate in study instruments.
• Patients who are pregnant or nursing.
• Patients with significant cardiopulmonary disease other than asthma, including cystic fibrosis, alpha-1-antitrypsin deficiency, interstitial lung disease, tracheo-/bronchomalacia, or cyanotic congenital cardiac defect.
• Patients with glaucoma, myasthenia gravis, or bladder neck obstruction (anticholinergics can worsen these conditions).
• Patients currently taking another anticholinergic medication

• Minimum Eligible Age: 7 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Center for Advancing Translational Sciences (NCATS)

NIH

Sponsor Role: collaborator

State University of New York at Buffalo

OTHER

Sponsor Role: lead

Responsible Party

Heather Lehman

Clinical Associate Professor of Pediatrics

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Heather K Lehman, MD

Role: PRINCIPAL_INVESTIGATOR

SUNY at Buffalo School of Medicine and Biomedical Sciences

Locations

Women and Children's Hospital of Buffalo

Buffalo, New York, United States

Countries

United States

Other Identifiers

UL1TR001412

Identifier Type: NIH

Identifier Source: secondary_id

View Link

STUDY00000774

Identifier Type: -

Identifier Source: org_study_id