Ventilatory Heterogeneity in Participants With Asthma (MK-0476-513)

NCT01621386 | Completed Phase 1

• 2 other identifiers: Pro00038169MK-0476-513
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

This study will explore the utility of magnetic resonance imaging (MRI) to assess ventilatory defects that occur due to asthma, determine the sensitivity and specificity of MRI in response to drug treatment, and whether MRI can serve as a biomarker of treatment effects due to asthma therapy.

Conditions

Asthma

Outcome Measures

Primary Outcomes (5)

• Change from baseline in VH assessed by oxygen-enhanced 1H MRI (Oe 1H MRI) after two weeks of montelukast or prednisone treatment

  Baseline and after two weeks of drug treatment

• Change from baseline in VH assessed by 19F-perfluoropropane MRI (19F MRI) after two weeks of montelukast or prednisone treatment

  Baseline and after two weeks of drug treatment

• Change from baseline in VH assessed by Lung Clearance Index (LCI) after two weeks of montelukast or prednisone treatment

  Baseline and after two weeks of drug treatment

• Change from baseline in VH assessed by Conducting Airway Heterogeneity (Scond) after two weeks of montelukast or prednisone treatment

  Baseline and after two weeks of drug treatment

• Change from baseline in VH assessed by Forced Expiratory Volume in 1 second (FEV1) after two weeks of montelukast or prednisone treatment

  Baseline and after two weeks of drug treatment

Secondary Outcomes (3)

• Comparison of VH assessed by Oe 1H MRI, 19F MRI, LCI, Scond and FEV1 at baseline

  Baseline

• Short-term test-retest repeatability of VH by Oe 1H MRI and 19F MRI

  Visit 2 and Visit 3

• Mid-term test-retest repeatability of VH by Oe 1H MRI and 19F MRI

  Visit 3 and Visit 4/Visit 5

Study Arms (1)

All Participants

EXPERIMENTAL

Participants (male or female) that are between 18-65 years of age with a clinical diagnosis of asthma will take montelukast for 2 weeks (treatment period 1) and then take prednisone for 2 weeks (treatment period 2)

Drug: Montelukast; Drug: Prednisone

Interventions

Montelukast DRUG

Administered orally as a single daily 10 mg dose for 2 weeks

Also known as: Singulair

All Participants

Prednisone DRUG

Administered orally as a single daily 20 mg dose for 2 weeks

All Participants

Eligibility Criteria

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

You may qualify if:

• Patient is a male or female 18 to 65 years of age with clinical diagnosis of asthma for at least 1 year at the prestudy (screening) visit.
• For female patients of reproductive potential, a blood pregnancy test will be performed, and it must be negative before the patient can continue in this study. If sexually active, the patient must agree to use appropriate contraceptive measures for the duration of the study and for 2 weeks after Visit 5. Medically acceptable contraceptives include: (1) surgical sterilization (such as a tubal ligation or hysterectomy), (2) approved hormonal contraceptives (such as birth control pills, patches, implants or injections), (3) barrier methods (such as a condom or diaphragm) used with a spermicide, or (4) an intrauterine device (IUD). Contraceptive measures such as Plan B™, sold for emergency use after unprotected sex, are not acceptable methods for routine use.
• Patient understands the study procedures and agrees to participate in the study by giving written informed consent (Consent must be given before any study procedures are performed)
• Patient is willing to comply with the study restrictions and adhere to the visit/protocol schedules.
• Patient is judged to be in good health (except for asthma) based on medical history, physical examination, vital sign measurements, and laboratory safety tests performed at the prestudy (screening) visit and/or prior to administration of the initial dose of study drug and has no evidence of cardiac, endocrine, or metabolic disease.
• Patient has a Body Mass Index (BMI) ≤ 39 kg/m2 at the prestudy screening (Visit 1). BMI is calculated by taking the patient's weight in kg and dividing by the patient's height in meters, squared. Patient's body must fit within the scanner sufficiently well to allow satisfactory imaging in the opinion of the investigator.
• Patient is a current non-smoker or if patient has a history of smoking, has not smoked for at least 6 months and has a smoking history of no more than 5 pack-years (i.e., 1 pack per day for 5 years). Patients who have discontinued smoking or the use of nicotine / nicotine containing products for at least approximately 3 months may be enrolled in the study at the discretion of the investigator.
• Patient has been defined by the study site team as having allergic asthma.
• Patient is able to perform reproducible pulmonary function testing (i.e., the 2 best acceptable spirograms have FEV1 values that do not vary by more than 5% of the largest value or more than 100 mL, whichever is greater).
• Patient has no clinically significant abnormality on electrocardiogram (ECG) performed at the prestudy (screening) visit and/or prior to administration of the initial dose of study drug.
• Patient has no contraindication to MRI exam.
• Known diagnosis of asthma for at least one year as defined by NHLBI NAEPP guidelines. (http://www.nhlbi.nih.gov/guidelines/asthma/execsumm.pdf).
• FEV1 \> 80% predicted
• Either reversibility of airflow obstruction after 4 puffs inhaled albuterol of 12% in either the FEV1 or FVC, or hyperresponsiveness by methacholine with PC20 FEV1 \< 16 mg/ml.
• Asthma Control Questionnaire score \< 1.25 consistent with good control

You may not qualify if:

• Patient is mentally or legally incapacitated, has significant emotional problems at the time of Screening (Visit 1) or expected during the conduct of the study or has a history of a clinically significant psychiatric disorder over the last 5 years. Subjects who have had situational depression may be enrolled in the study at the discretion of the investigator.
• Patient has taken an investigational product within 4 weeks prior to the prestudy (screening) visit. The 4 week window will be derived from the date of the last dose of study drug in the previous study to the prestudy/screening visit of the current study.
• Patient has a history of any illness that, in the opinion of the study investigator, might confound the results of the study or poses an additional risk to the subject by their participation in the study including, but not limited to, diabetes mellitus, hypertension, osteoporosis, as well as poorly controlled concomitant conditions that include obstructive sleep apnea (OSA), gastroesophageal reflux disease (GERD), and chronic sinusitis/rhinitis.
• Students or employees who are under direct supervision by any of the investigators in this protocol are not eligible to participate.
• Patient has significant or unexplained abnormalities on the physical examination and/or laboratory safety tests at Visit 1.
• Patient has a blood pressure of \>150 mm Hg systolic or \>95 mm Hg diastolic on \>2 measurements done \>5 minutes apart at Visit 1 or Visit 2.
• Patient has ECG abnormalities consistent with previous myocardial infarction, hypertrophic cardiomyopathy, ischemic heart disease or conduction system disease.
• Patient has evidence of illness that would require treatment with an excluded medication, could be immediately life threatening (e.g., arrhythmias, congenital heart disease), would pose a restriction on participation or successful completion of the study, or would pose an additional risk to administering montelukast to the patient.
• History of intubation due to asthma within the last five (5) years.
• FEV1 \< 45% predicted
• Hospitalization within previous 6 months
• Patient has had major surgery, donated or lost 1 unit of blood (approximately 500 mL) within 8 weeks prior to the prestudy (screening) visit.
• m. Patient has a history of significant multiple and/or severe allergies to medications used (or potentially used) in this study (including albuterol, montelukast, prednisone, acetaminophen, lidocaine, fentanyl, atropine, and midazolam as well as latex), or has had an anaphylactic reaction or significant intolerability to a marketed or investigational prescription or non-prescription drug or to food.
• Patient has a history of stroke, chronic seizures, or major neurological disorder.
• Patient has a history of neoplastic disease.

Sponsors & Collaborators

• Hal C Charles: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27705, United States

Location

MeSH Terms

Conditions

Asthma

Interventions

montelukast; Prednisone

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Cecil Charles, PhD

  Duke University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: June 14, 2012
• First Posted: June 18, 2012
• Study Start: January 1, 2013
• Primary Completion: September 1, 2015
• Study Completion: March 1, 2016
• Last Updated: April 20, 2017

Record last verified: 2017-04

Locations

US (1)