Human Safety of Capsaicin Inhalation Challenge Testing for Young and Older Men

NCT01621685 | Completed Phase 1

• 1 other identifier: IND# 69,642
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

In 2004, the investigators initiated a human Capsaicin inhalation experiment under an Investigational New Drug (IND) protocol approved by the FDA (IND 69,642) and the subject safety procedures instituted and approved by the Institutional Review Board (IRB). As part of the study protocol, inhaled Capsaicin solutions were analyzed using high performance liquid chromatography (HPLC). The investigation employed safety procedures while conducting the human inhalation investigations. In addition, during our investigations we observed discrepancies between the predicted Capsaicin concentrations mixed by a registered pharmacist and the actual capsaicin concentrations determined by HPLC. The stability of Capsaicin solutions stored over a seven month period and refrigerated at 4degrees C and protected against ultraviolet light were examined.

Conditions

COPD

Keywords

Capsaicin; Cough; Cough reflex; Inhalation agents; Inhalation challenge; TRPV1 receptor

Outcome Measures

Primary Outcomes (1)

• >12% Fall In FEV1

  Single breaths of capsaicin were delivered in ascending order, with normal saline solution randomly interspersed to increase challenge blindness, until two (C2) and five (C5) or more coughs were reached. The different concentrations were delivered at 2 minute intervals. After each inhalation dose the following were performed: FEV1 measurement, administer of the symptom questionnaire and auscultation of the chest for wheezing.

  Baseline and >5 coughs 2-minutes after each inhaled capsaicin dose

Secondary Outcomes (1)

• Symptom Questionnaire

  Repeatedly over 1 week

Study Arms (1)

Spirometry, auscultation, questionnaire

EXPERIMENTAL

\>12% fall in FEV1, wheezing on auscultation, symptom questionnaire score \>4

Biological: biological/vaccine

Interventions

biological/vaccine BIOLOGICAL

Inhalation studies will immediately be terminated after a significant adverse response to a particular capsaicin dose and no further testing will occur.

Also known as: >12% fall in FEV1, wheezing on chest auscultation or >4 on Symptom Questionnaire

Spirometry, auscultation, questionnaire

Eligibility Criteria

• Age: 19 Years - 92 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men of ages 18 and 30 (Dates of birth 1973-1985) or 55-92 years old (Dates of birth 1911-1948).
• Must not currently be a cigarette smoker. If an ex-smoker then has not smoked for at least 10 years and consumption were no more than 10 pack years.
• Agrees to volunteers for the study and willing to sign the informed consent form.
• There were negative/normal screening tests for the following
• Responses to the questionnaire deny current and prior respiratory diseases (including asthma, emphysema, chronic bronchitis, sinusitis and interstitial lung d9sase) and no current respiratory complaints (e.g., cough, wheezing, shortness of breath, allergic rhinitis, and sinusitis). Subjects must not be taking any cardiac medications or admit to a physician-diagnosed cardiac condition.
• "Normal" spirometry measurements with FEV1 \& FVC greater than 75% predicted and FEV1/FVC more than 69%
• Impedance oscillometry were within normal limits
• "Negative" physical examination of the chest with absence of wheezing and crackles on auscultation of the chest.
• Exhaled nitric oxide concentration is less than 35 ppb for younger and less than 65 ppb for older groups

You may not qualify if:

• men of: ages \< 18, 31-54 and \>92 years old;
• current cigarette smokers or exsmokers who have smoked within the past 10 years and/or smoked more than 10 pack/years;
• refusal to volunteer for the study and not willing to sign the informed consent form;
• screening test not considered "normal" by physician/PI and showing one or more of the following:
• one or more positive response to the questionnaire(e.g., current or past respiratory diseases including asthma, emphysema, chronic bronchitis, sinusitis and interstitial lung disease; and/or; current respiratory complaints (e.g., cough, wheezing, shortness of breath, allergic rhinitis, and sinusitis) and/or; admitting to taking a cardiac medication and/or; or physician-diagnosed cardiac condition (e.g., coronary heart disease, angina, myocardial infarction, valvular heart disease, cardiomyopathy, etc.);
• Abnormal spirometry measurements (FEV1 \&/or FVC \<75% predicted and FEV1/FVC \<69%);
• "Positive" physical examination (performed by Physician/PI) with presence of wheezing and/or crackles on auscultation of the chest;
• Impulse oscillometry \>4 times normal limits;
• Exhaled nitric oxide of \>35ppb for younger group and \>65 ppb for older group. -

Sponsors & Collaborators

• University of South Florida: lead
• Centers for Disease Control and Prevention: collaborator

Study Sites (1)

College of Public Health

Tampa, Florida, 33612, United States

Location

Related Publications (1)

• Szallasi A, Blumberg P. Vanilloid (Capsaicin) Receptors and Mechanisms. Pharmacol Reviews 1999; 51:159-211 -Dicpinigaitis PV, Alva RV. Safety of capsaicin. Chest 2005; 128:196-202 -Dicpinigaitis PV. Cough reflex sensitivity in cigarette smokers. Chest 2003; 123:685-688 -Dicpinigaitis PV. Short- and long-term reproducibility of capsaicin cough challenge testing. Pulm Pharmacol Ther 2003; 16:61-65 -Broeders MEAC, Molema J, Hop WCJ, et al. Bronchial challenge, assessed with forced expiratory maneuvers and airway impedance. Respiratory Medicine 2005; 99:1046-1052 - Gordon R, Haight R, Brooks, SM.. Role of Age on Exhaled breath nitric oxide. Lung 2006 -Cortright DN, Szallas, A. Biochemical pharmacology of the vanilloid receptor TRPV1: An update. Eur. J. Biochem 1994; 271:1841-1819 -Kopec SE, DeBellis RJ, Irwin, RS. Chemical analysis of freshly prepared and stored capsaicin solutions: Implications for tussigenic challenges. Pulm Pharmacol Therapetics 2002; 15:529-534.

  RESULT

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Cough

Interventions

Biological Products; Vaccines; Accidental Falls

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Respiration Disorders; Signs and Symptoms, Respiratory; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Complex Mixtures; Accidents; Public Health; Environment and Public Health

Study Officials

• Stuart M. Brooks, MD

  University of South Florida

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: August 5, 2010
• First Posted: June 18, 2012
• Study Start: September 1, 2004
• Primary Completion: September 1, 2007
• Study Completion: September 1, 2007
• Last Updated: June 18, 2012

Record last verified: 2012-06

Locations

US (1)