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.
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
|Official Title:||The Role of Age on the Human Cough Reflex|
- >12% Fall In FEV1 [ Time Frame: Baseline and >5 coughs 2-minutes after each inhaled capsaicin dose ] [ Designated as safety issue: Yes ]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.
- Symptom Questionnaire [ Time Frame: Repeatedly over 1 week ] [ Designated as safety issue: Yes ]Over a 1-week period, repeated telephone calls recorded responses to 6 questions. Subjects were asked post-inhalation symptoms of: (1) heavy or difficulty in breathing; (2) phlegm production: (3) runny or irritated nose; (4) throat irritation or burning: (5) feeling of a weight or tightness of the chest; and, (6) feeling of chest burning. Any subject reporting continued symptoms of category #4 (i.e., very severe) for two or more items, compared to the baseline was asked to return for more detailed evaluation.
|Study Start Date:||September 2004|
|Study Completion Date:||September 2007|
|Primary Completion Date:||September 2007 (Final data collection date for primary outcome measure)|
Experimental: Spirometry, auscultation, questionnaire
>12% fall in FEV1, wheezing on auscultation, symptom questionnaire score >4
Inhalation studies will immediately be terminated after a significant adverse response to a particular capsaicin dose and no further testing will occur.
Other Name: >12% fall in FEV1, wheezing on chest auscultation or >4 on Symptom Questionnaire
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.
|United States, Florida|
|College of Public Health|
|Tampa, Florida, United States, 33612|
|Principal Investigator:||Stuart M. Brooks, MD||University of South Florida|