Human Safety of Capsaicin Inhalation Challenge Testing for Young and Older Men
Human Safety of Capsaicin Inhalation Challenge Testing for Young and Older Men
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.
After a research subject's death during an inhalation study using medications/drugs not
 approved for this route, the FDA prohibited human use of non-approved chemicals including
 capsaicin administered via inhalation.

 Capsaicin inhalation challenge tests (CICT) were performed on forty men of different ages
 utilizing pharmaceutical grade Capsaicin. Solutions were mixed by a registered pharmacist and
 Capsaicin doses, administered to subjects, were analyzed by high performance liquid
 chromatography (HPLC). Capsaicin solutions were stored in a refrigerator at 4 degrees C and
 shielded from ultraviolet light for 7 months. There was serial monitoring by spirometry and
 impulse oscillometry, electrocardiography, blood pressure, pulse and oxygen saturation
 measurements.

 There were no adverse reactions at any dose, including the highest capsaicin concentration.
 Serial spirometry and impulse oscillometry, electrocardiography, blood pressure, pulse and
 oxygen saturation measurements did not change. The actual amount of pharmaceutical-grade
 capsaicin measured was 85.5% of the concentrations estimated by the registered pharmacist at
 time of mixing. The difference was more for the lowest 0.49 uMol dose (28.1) compared to a
 2.2% lesser concentration for the 1000 uMol solution. Capsaicin concentrations fell after 3
 months of storage.

 Dilute capsaicin aerosol inhalation is relatively innocuous and CICT is safe. The actual
 amount of pharmaceutical-grade capsaicin inhaled by subjects is less than the estimate at
 mixing. Capsaicin loses potency after 3-months of protected storage. Inhalation studies
 involving non-approved drugs or chemicals/medications can be safely conducted when they
 follow the appropriate safety procedures such as described in this investigation.
Inclusion Criteria:

 1. Men of ages 18 and 30 (Dates of birth 1973-1985) or 55-92 years old (Dates of birth
 1911-1948).

 2. 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.

 3. Agrees to volunteers for the study and willing to sign the informed consent form.

 4. There were negative/normal screening tests for the following

 1. 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.

 2. "Normal" spirometry measurements with FEV1 & FVC greater than 75% predicted and
 FEV1/FVC more than 69%

 3. Impedance oscillometry were within normal limits

 4. "Negative" physical examination of the chest with absence of wheezing and
 crackles on auscultation of the chest.

 5. Exhaled nitric oxide concentration is less than 35 ppb for younger and less than
 65 ppb for older groups

 Exclusion Criteria:

 1. men of: ages < 18, 31-54 and >92 years old;

 2. current cigarette smokers or exsmokers who have smoked within the past 10 years and/or
 smoked more than 10 pack/years;

 3. refusal to volunteer for the study and not willing to sign the informed consent form;

 4. screening test not considered "normal" by physician/PI and showing one or more of the
 following:

 1. 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.);

 2. Abnormal spirometry measurements (FEV1 &/or FVC <75% predicted and FEV1/FVC
 <69%);

 3. "Positive" physical examination (performed by Physician/PI) with presence of
 wheezing and/or crackles on auscultation of the chest;

 4. Impulse oscillometry >4 times normal limits;

 5. Exhaled nitric oxide of >35ppb for younger group and >65 ppb for older group. -