Asthma Exacerbations and Vascular Function

NCT02630511 | Completed

• 1 other identifier: Pro00047054
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

Brief Summary

Although asthma is a disease of the airways, research is now showing that asthmatics are more likely to develop cardiovascular disease (CVD) compared to non-asthmatics. Vascular dysfunction is seen in people at high risk of CVD and has been linked to inflammation. During an asthma attack, levels of inflammation in the whole body increase, which could potentially explain why asthmatics are at increased risk of CVD. By exercising, people can change the amount of inflammation in their bodies, improve vascular function, and thereby reduce the risk of CVD. In the proposed study the investigators will assess if asthma attacks lead to increased risk of CVD by evaluating inflammatory levels and vascular function before and after asthma attacks. The investigators will also evaluate if exercise reduces the cardiovascular risk following asthma attacks. The results from this study will help in understanding why asthmatics are at increased risk of CVD.

Conditions

Asthma

Outcome Measures

Primary Outcomes (1)

• Change from baseline flow-mediated dilation (FMD) to 15 minutes and 1 hour following bronchial challenge

  Flow-mediated dilation (FMD) of the brachial artery following 5 minutes of forearm occlusion will be measured using ultrasound (8L-RS 4.0-13.0 MHz probe, Vivid q, GE Healthcare, Mississauga, ON) and FMD data will be analyzed using FDA approved software available from Medical Imaging Applications (Coralville, IA, USA). FMD will be calculated as: (peak hyperemic diameter-baseline diameter)/baseline diameter x 100. FMD will be normalized for baseline diameter. Peak hyperemic brachial arterial velocity (and subsequently shear stress) will be determined using Doppler ultrasound, and used for normalization of FMD.

  At baseline, 15 min, 1 hour, and 24 hours following each intervention

Secondary Outcomes (4)

• Change from baseline arterial stiffness (cPWV) to 15 minutes and 1 hour following bronchial challenge

  At baseline, 15 min, 1 hour, and 24 hours following each intervention

• Change from baseline arterial stiffness (pPWV) to 15 minutes and 1 hour following bronchial challenge

  At baseline, 15 min, 1 hour, and 24 hours following each intervention

• Change from baseline systemic inflammation to 15 minutes and 1 hour following bronchial challenge

  At baseline, 15 min, 1 hour, and 24 hours following each intervention

• Change from baseline pulmonary inflammation to 15 minutes and 1 hour following bronchial challenge

  At baseline, 15 min, 1 hour, and 24 hours following each intervention

Study Arms (2)

Asthma Group

EXPERIMENTAL

Asthma group to receive mannitol, methacholine or placebo challenge tests

Drug: Mannitol; Drug: Methacholine; Drug: Placebo; Other: Rest; Other: Exercise

Control Group

EXPERIMENTAL

Control group to receive mannitol, methacholine or placebo challenge tests

Drug: Mannitol; Drug: Methacholine; Drug: Placebo; Other: Rest; Other: Exercise

Interventions

Mannitol DRUG

Mannitol consists of inhaling 0 (empty capsule acting as a placebo), 5, 10, 20, 40, 80, 160, 160, and 160 mg mannitol, resulting in a maximum cumulative dose of 635 mg

Also known as: Mannitol Challenge Test

Asthma Group; Control Group

Methacholine DRUG

Methacholine consists of inhaling 0.0625 mg/mL, 0.25 mg/mL, 1 mg/mL, 4 mg/mL, and 16 mg/mL

Also known as: Methacholine Challenge Test

Asthma Group; Control Group

Placebo DRUG

Placebo consists of inhaling humidified air

Also known as: Placebo Challenge Test

Asthma Group; Control Group

Rest OTHER

Asthma Group; Control Group

Exercise OTHER

Asthma Group; Control Group

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Asthmatics, defined according to ATS and GINA guidelines,
• BMI \<35kg/m2
• No known cardiovascular disease
• ACQ score equal to or less than 1.5 (controlled or partly controlled asthma)
• People without asthma (controls) will be recruited from the general population according to the same criteria, but with no history of asthma.

You may not qualify if:

• Pregnancy

Sponsors & Collaborators

• University of Alberta: lead

Study Sites (1)

Clinical Physiology Research Laboratory

Edmonton, Alberta, T6G 2J1, Canada

Location

Related Publications (1)

• Moore LE, Brotto AR, Fuhr DP, Rosychuk RJ, Wong E, Bhutani M, Stickland MK. Impact of airway challenges on cardiovascular risk in asthma - a randomized controlled trial. PLoS One. 2023 Jul 17;18(7):e0288623. doi: 10.1371/journal.pone.0288623. eCollection 2023.

  PMID: 37459335 DERIVED

MeSH Terms

Conditions

Asthma

Interventions

Mannitol; Methacholine Chloride; RE1-silencing transcription factor; Exercise

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Sugar Alcohols; Alcohols; Organic Chemicals; Carbohydrates; Methacholine Compounds; Trimethyl Ammonium Compounds; Quaternary Ammonium Compounds; Amines; Onium Compounds; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Officials

• Michael K Stickland, PhD

  University of Alberta

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized double-blind cross over design

Study Record Dates

• First Submitted: December 4, 2015
• First Posted: December 15, 2015
• Study Start: December 1, 2015
• Primary Completion: December 1, 2020
• Study Completion: December 1, 2020
• Last Updated: July 1, 2021

Record last verified: 2021-06

Locations

CA (1)