Clinical trial NCT03223350
Conditions: Cyclical Vomiting
Sponsor: Henry Ford Health System
Start date: 2017-12-20; Completion date: 2019-08-05
Enrollment: 30 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a phase 2 randomized controlled trial testing the effect of topical capsaicin for the relieve of nausea and vomiting.

Detailed description:

Arms: arm 1: 0.1% capsaicin cream, one application arm 2: Topical cream with no active drug
Interventions: intervention 1: Capsaicin 0.1% Cream intervention 2: Placebos
Intervention descriptions: intervention 1: Topical application intervention 2: placebo cream

Protocol documents:
Prot_002.pdf: 
Topical Capsaicin Cream for Treatment of Suspected 
Cyclical Vomiting Syndromes   
 
NCT03223350 
 
Date: April 5, 2017 


Study Design and Setting  
        This randomized, double-blind, placebo-controlled pilot trial was performed at an urban academic 
trauma center hospital with 100,000 annual ED visits. The study was approved by the institutional 
review board and registered with the National Library of Medicine (NCT03223350). Research team 
members screened patients using the electronic medical record system. We obtained written informed 
consent from all participants. Patients were enrolled between December 2017 and July 2019. 
        All adult patients (age ≥ 18 years) presenting with a suspected exacerbation of CHS and had active 
vomiting or nausea in the ED were eligible. Exclusion criteria were: minors (< 18 years old), pregnancy, 
known allergy to capsaicin or hot peppers, those with resolution of nausea prior to randomization, 
outpatient use of prescription antiemetics within the past 24- hours, acute infectious or surgical 
abdominal conditions, and inability to provide informed consent. The original protocol excluded patients 
that received any antiemetic medication in the ED prior to enrollment. Half-way through the trial, we 
made a protocol change that removed this exclusion criteria and allowed enrollment of patients that 
received an antiemetic medication in the ED prior to randomization as long as nausea was still present. 
We made this protocol change due to the difficulty obtaining consent and enrolling symptomatic 
patients prior to receiving standard antiemetic therapy.  
  
Interventions, Randomization, and Blinding 
          Research team members assessed eligibility among all patients who presented with suspected 
CHS. Any potentially eligible female patients of childbearing age had to have a pregnancy test performed 
prior to enrollment. We randomized patients that provided informed consent to the experimental or 
control group using REDCap database (Research Electronic Data Capture, Vanderbilt University). 
Randomization used 1:1 allocation and stratified by gender. The treatment consisted of five grams of 
topical 0.1% capsaicin cream, and the placebo consisted of a moisturizing cream. The study team pre-
packaged the capsaicin and placebo creams in identical single-dispensing tubes and coded each with a 
study identification number. The capsaicin cream and the placebo were identical in appearance and had 
no scent. An ED nurse applied study medication cream once to the abdomen in a uniform manner. The 
treating physicians, research team members, and patients were blinded to study drug allocation. In 
addition to study medication, patients received conventional therapy, which was determined by the 
treating physician independent of study enrollment.  
 
Methods and Measurements 
         Research team members collected relevant patient demographic, clinical, and treatment data and 
entered data into a secure REDCap. We measured the intensity of the patient’s nausea upon 
randomization and at 30- and 60-minutes following application of study medication. For nausea 
assessment, we used a previously validated visual analog scale (VAS) that ranged from 0 to 10 cm (10 
being most severe).18,19 A research team member remained at the patient’s bedside for the first 60 
minutes to assess for any immediate adverse events. Additionally, the patient was assessed for any 
adverse events over the entire course of the patient’s ED stay and, later, through a phone call at 30 
days. 


 
Outcomes 
        The primary outcome was the patient’s reported nausea on the VAS at 30 minutes following study 
medication application. Secondary outcomes were the patient’s reported nausea and percent change 
from baseline at 60 minutes, disposition status (hospital admission or discharge), and the need for 
rescue anti-emetic medication. The 30- and 60-minutes outcome assessment times were based on 
clinical experience that capsaicin has a rapid effect (<30 minutes) but may have a delayed maximum 
effect. Hospital admission included placement on observation or inpatient units. 

SAP_003.pdf: 
Topical Capsaicin Cream for Treatment of Suspected 
Cyclical Vomiting Syndromes   
 
NCT03223350 
 
Date: May 1, 2019 


Statistical Analysis Plan 
           Assuming a clinically meaningful effect size of 3 cm difference in the nausea VAS 
(primary outcome) between capsaicin and placebo groups and standard deviation of 2.5 cm, we 
estimate that we would require 12 subjects in each of two groups to allow for 80% power and 
alpha 0.05. To account for imprecision in the effect size and the unknown factor of early 
treatment withdrawal due to skin irritation, we planned a total sample size of 30 participants. 
We evaluated baseline characteristics of the overall cohort using descriptive statistics 
and report discrete data as frequencies and percentages and continuous data as medians and 
interquartile ranges. For all outcomes, we used intention-to-treat analysis. For one patient in the 
capsaicin group, the nausea VAS at 30 and 60 minutes was missing; we used multiple 
imputation to assign these values. Analysis included Chi-square test or Fisher’s exact test for 
unadjusted comparisons of categorical outcomes between treatment groups. Analysis also 
included student’s t-test, or Mann-Whitney U test, as appropriate for unadjusted comparisons of 
continuous variables between treatment groups. A p-value <0.05 (two-tailed) was considered 
statistically significant for all tests. We performed all analyses using SAS 9.4 (Cary, NC) and 
report primary results with 95% confidence intervals (CI).