The Effects of Different Long-acting Bronchodilator Medications on Asthma Patients With Different Genetic Variations

NCT00706446 | Terminated Results

• 1 other identifier: 2008-P-000285
• Study Type: interventional
• Target: 255
• Locations: 1 country
• Sites: 2

Brief Summary

This study is looking at the effects of certain long-acting bronchodilators on patients with asthma who have specific genetic variations. The investigators are interested in a certain common genetic variation in the receptor for beta-agonists, which is found in as many of one-sixth of the population. There is evidence that patients with asthma who have this variation may not do as well when treated with albuterol on a regular basis. The investigators will be looking at whether patients with this variation have more asthma exacerbations over the course of a year when treated with salmeterol or formoterol, which are long-acting forms of albuterol; and whether these patients have fewer exacerbations when treated with tiotropium, which is a different long-acting bronchodilator that does not act at this receptor. In both groups patients will also be receiving inhaled steroids.

Conditions

Asthma

Keywords

Asthma; Pharmacogenetics; Beta agonists; salmeterol; formoterol; tiotropium; beta adrenergic receptor; single nucleotide polymorphism

Outcome Measures

Primary Outcomes (1)

• Number of Patients With Asthma Exacerbation

  1 year

Secondary Outcomes (4)

• FEV1 (Forced Expiratory Volume)

  1 year

• Exhaled NO (Nitric Oxide)

  1 year

• Symptom-free Days

  1 year

• Asthma-related Quality of Life

  1 year

Study Arms (6)

1 - Tio/ICS in the Arg/Arg genotype

EXPERIMENTAL

Tiotropium bromide 18 mcg qd plus inhaled steroids, either Fluticasone propionate Diskus 100 mcg 1 puff bid, Fluticasone propionate aerosol 44 mcg 2 puffs bid, Fluticasone propionate aerosol 110 mcg 2 puffs bid, Fluticasone propionate aerosol 220 mcg 2 puffs qd, Budesonide 90 mcg 2 puffs bid, or Budesonide 180 mcg 2 puffs bid, in the Arg/Arg genotype

Drug: tiotropium bromide; Drug: Fluticasone propionate; Drug: budesonide

2 - Tio/ICS in the Arg/Gly genotype

EXPERIMENTAL

Tiotropium bromide 18 mcg QD plus inhaled steroids, either Fluticasone propionate Diskus 100 mcg 1 puff bid, Fluticasone propionate aerosol 44 mcg 2 puffs bid, Fluticasone propionate aerosol 110 mcg 2 puffs bid, Fluticasone propionate aerosol 220 mcg 2 puffs qd, Budesonide 90 mcg 2 puffs bid, or Budesonide 180 mcg 2 puffs bid, in the Arg/Gly genotype

Drug: tiotropium bromide; Drug: Fluticasone propionate; Drug: budesonide

3 - Tio/ICS in the Gly/Gly genotype

EXPERIMENTAL

Tiotropium bromide 18 mcg QD plus inhaled steroids, either Fluticasone propionate Diskus 100 mcg 1 puff bid, Fluticasone propionate aerosol 44 mcg 2 puffs bid, Fluticasone propionate aerosol 110 mcg 2 puffs bid, Fluticasone propionate aerosol 220 mcg 2 puffs qd, Budesonide 90 mcg 2 puffs bid, or Budesonide 180 mcg 2 puffs bid, in the Gly/Gly genotype

Drug: tiotropium bromide; Drug: Fluticasone propionate; Drug: budesonide

4 - LABA/ICS in the Arg/Arg genotype

ACTIVE COMPARATOR

Salmeterol 50 mcg 1 puff BID or Formoterol 12mcg 1 puff BID plus inhaled steroid, either Fluticasone propionate Diskus 100 mcg 1 puff bid, Fluticasone propionate aerosol 44 mcg 2 puffs bid, Fluticasone propionate aerosol 110 mcg 2 puffs bid, Fluticasone propionate aerosol 220 mcg 2 puffs qd, Budesonide 90 mcg 2 puffs bid, or Budesonide 180 mcg 2 puffs bid, in the Arg/Arg genotype

Drug: Salmeterol; Drug: Formoterol; Drug: Fluticasone propionate; Drug: budesonide

5 - LABA/ICS in the Arg/Gly genotype

ACTIVE COMPARATOR

Salmeterol 50 mcg 1 puff BID or Formoterol 12mcg 1 puff BID plus inhaled steroid, either Fluticasone propionate Diskus 100 mcg 1 puff bid, Fluticasone propionate aerosol 44 mcg 2 puffs bid, Fluticasone propionate aerosol 110 mcg 2 puffs bid, Fluticasone propionate aerosol 220 mcg 2 puffs qd, Budesonide 90 mcg 2 puffs bid, or Budesonide 180 mcg 2 puffs bid, in the Arg/Gly genotype

Drug: Salmeterol; Drug: Formoterol; Drug: Fluticasone propionate; Drug: budesonide

6 - LABA/ICS in the Gly/Gly genotype

ACTIVE COMPARATOR

Salmeterol 50 mcg 1 puff BID or Formoterol 12mcg 1 puff BID plus inhaled steroid, either Fluticasone propionate Diskus 100 mcg 1 puff bid, Fluticasone propionate aerosol 44 mcg 2 puffs bid, Fluticasone propionate aerosol 110 mcg 2 puffs bid, Fluticasone propionate aerosol 220 mcg 2 puffs qd, Budesonide 90 mcg 2 puffs bid, or Budesonide 180 mcg 2 puffs bid, in the Gly-Gly genotype

Drug: Salmeterol; Drug: Formoterol; Drug: Fluticasone propionate; Drug: budesonide

Interventions

tiotropium bromide DRUG

tiotropium bromide one inhalation a day for one year, along with inhaled steroids at variable dosing based on patient's prior inhaled steroid dosing and treating physician's judgement.

Also known as: Spiriva

1 - Tio/ICS in the Arg/Arg genotype; 2 - Tio/ICS in the Arg/Gly genotype; 3 - Tio/ICS in the Gly/Gly genotype

Salmeterol DRUG

salmeterol diskus 1 puff twice a day for 1 year, depending on which medication the patient was on before the start of the trial. The goal of this intervention is to continue the patient's current therapy of long-acting beta-agonists. In addition, the patients will be on inhaled steroids at variable doses, depending on what dose they were on at the start of the trial and based on the judgement of their treating physicians.

Also known as: Serevent

4 - LABA/ICS in the Arg/Arg genotype; 5 - LABA/ICS in the Arg/Gly genotype; 6 - LABA/ICS in the Gly/Gly genotype

Formoterol DRUG

formoterol aerolizer 12 mcg 1 puff twice a day for 1 year, depending on which medication the patient was on before the start of the trial. The goal of this intervention is to continue the patient's current therapy of long-acting beta-agonists. In addition, the patients will be on inhaled steroids at variable doses, depending on what dose they were on at the start of the trial and based on the judgement of their treating physicians.

Also known as: Foradil

4 - LABA/ICS in the Arg/Arg genotype; 5 - LABA/ICS in the Arg/Gly genotype; 6 - LABA/ICS in the Gly/Gly genotype

Fluticasone propionate DRUG

Either fluticasone propionate diskus 100 mcg 1 puff twice a day or fluticasone propionate aersol in 44 mcg, 110 mcg, 2 puffs twice a day OR fluticasone propionate 220 mcg 2 puffs once a day for one year, depending on which dose the patient was on before the start of the trial.

Also known as: Flovent

1 - Tio/ICS in the Arg/Arg genotype; 2 - Tio/ICS in the Arg/Gly genotype; 3 - Tio/ICS in the Gly/Gly genotype; 4 - LABA/ICS in the Arg/Arg genotype; 5 - LABA/ICS in the Arg/Gly genotype; 6 - LABA/ICS in the Gly/Gly genotype

budesonide DRUG

Either budesonide 90 mcg 2 puffs twice a day or 180 mcg 2 puffs twice a day for one year, depending on which dose the patient was on before the start of the trial.

Also known as: Pulmicort Flexihaler

1 - Tio/ICS in the Arg/Arg genotype; 2 - Tio/ICS in the Arg/Gly genotype; 3 - Tio/ICS in the Gly/Gly genotype; 4 - LABA/ICS in the Arg/Arg genotype; 5 - LABA/ICS in the Arg/Gly genotype; 6 - LABA/ICS in the Gly/Gly genotype

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Clinical history consistent with asthma
• Has a current prescription for a long-acting beta agonist, either along or in combination with an inhaled corticosteroid (salmeterol, formoterol, fluticasone/salmeterol, or budesonide/formoterol)
• Ability to provide informed consent
• Non-smoker (total lifetime smoking history \< 10 pack-years; no more than five occasions of smoking any substance or using smokeless tobacco products in the past year)
• No smoking or use of smokeless tobacco in the past 30 days
• No known contraindication to inhaled tiotropium e.g. narrow angle glaucoma, history of bladder neck obstruction or significant symptoms related to prostatic hypertrophy

You may not qualify if:

• Lung disease other than asthma
• Established or suspected diagnosis of vocal cord dysfunction
• Significant medical illness (other than asthma) that is not stable
• History of life-threatening asthma requiring treatment with intubation and mechanical ventilation within the past 5 years
• History of respiratory tract infection within the previous 4 weeks (only applies at screening visits)
• Hyposensitization therapy other than an established maintenance regimen
• Allergy to tiotropium
• Pregnancy or lactation. If potentially able to bear children, not using an acceptable form of birth control
• Inability to use inhaler devices
• Inability to participate over the one year period
• Current use of tiotropium

Sponsors & Collaborators

• Brigham and Women's Hospital: lead
• Baim Institute for Clinical Research: collaborator
• Massachusetts General Hospital: collaborator

Study Sites (2)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Related Links

• Brigham and Women's Hospital Asthma Research Center

MeSH Terms

Conditions

Asthma

Interventions

Tiotropium Bromide; Salmeterol Xinafoate; Formoterol Fumarate; Fluticasone; Budesonide

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Scopolamine Derivatives; Tropanes; Azabicyclo Compounds; Aza Compounds; Organic Chemicals; Alkaloids; Heterocyclic Compounds; Bridged Bicyclo Compounds, Heterocyclic; Heterocyclic Compounds, Bridged-Ring; Albuterol; Ethanolamines; Amino Alcohols; Alcohols; Amines; Phenethylamines; Ethylamines; Androstadienes; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pregnenediones; Pregnenes; Pregnanes

Results Point of Contact

• Title: Dr. Elliot Israel
• Organization: Brigham and Women's Hospital

eisrael@partners.org

6177328201

Study Officials

• Elliot Israel, MD

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of the Asthma Research Center

Study Record Dates

• First Submitted: June 25, 2008
• First Posted: June 27, 2008
• Study Start: June 1, 2008
• Primary Completion: June 1, 2010
• Study Completion: September 1, 2011
• Last Updated: May 31, 2017
• Results First Posted: May 1, 2017

Record last verified: 2017-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)