Human Safety of Capsaicin Inhalation Challenge Testing for Young and Older Men
Condition: COPD
Study type: Interventional
Phase: Phase 1

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.
    

Detailed description: 
      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.
    

Intervention name(s): biological/vaccine
Intervention type(s): Biological
Intervention description(s): Inhalation studies will immediately be terminated after a significant adverse response to a particular capsaicin dose and no further testing will occur.
Other intervention name(s): >12% fall in FEV1, wheezing on chest auscultation or >4 on Symptom Questionnaire
Intervention model: Single Group Assignment
Masking: None (Open Label)
Keywords: Capsaicin; Cough; Cough reflex; Inhalation agents; Inhalation challenge; TRPV1 receptor