Capsaicin for Cerebral Perfusion Augmentation (CCPA)

Effect of Capsaicin on the Augmentation of Cerebral Perfusion. A Phase II Study.

To determine the effect of capsaicin upon serial transcranial Doppler (TCD) markers of cerebral blood flow (CBF). Methods Serial TCD testing in 30 participants with cerebrovascular risk factors. Capsaicin doses .66 and .99 μMol. Outcomes: peak systolic and end-diastolic velocities in the middle cerebral artery (MCA), mean velocity (MV), pulsatility index (PI), CBF index, arterial pressure, and perceived pungency (PP) in five minutes intervals up to 20 minutes.

Study Overview

• Status: Completed
• Conditions: Cerebral Circulatory Disorder
• Intervention / Treatment: Drug: Capsaicin

Detailed Description

Subjects The study is expected to enroll 30 participants who will be recruited from the Internal Medicine outpatient clinic. Those willing to participate will be asked to sign the informed consent form (ICF) and will received the assigned dose of capsaicin. Half of the participants in each dose group will receive stimulation on either left or right side of the palate, but TCD measurements will be bilateral. Chemical stimuli From an initial 0.1% capsaicin (Sigma-Aldrich, St. Louis, MO) stock solution in 95% ethanol; solutions with 66 and 99 μMol/ml solutions will be obtained by diluting the stock solution with distilled water. One milliliter of each dilution was pipetted on to 2 cm filter paper squares. Then, the filter papers will be let dry. Immediately before application, filter papers will be rehydrated with 1 milliliter of distilled water. The rehydrated filter paper will be applied and will remain stationary on the subject's hemi palate's posterior surface during TCD measurements. Participants will be instructed not to swallow and to avoid touching the paper filter with their tongue for the 20 minutes of the experiment.

TCD testing With a TCD device (Philips Sonos 7500®) will include: peak systolic velocity (PSV) and end-diastolic velocity (EDV) in the middle cerebral artery (MCA) through the temporal window of the stimulated side. After a basal recording post stimulation recordings will initiate immediately after stimulation, and will be followed by serial recordings every five minutes and up to 20 minutes. At each time point the systolic pressure (SP), diastolic pressure (DP), and perceived pungency (PP) on a visual analog scale will be recorded. TCD markers of cerebral blood flow From the initial measurements the Mean velocity (MV) = EDV + [(PSVEDV) / 3], pulsatility index (PI) = PSV - EDV / MV, mean arterial pressure (MAP) = ((2 * DP) + SP) / 3 and, the CBF index (CBFi), CBFi = (MAP * 10) / 1.47^PI, will be calculated.

Statistical analysis Shapiro Wilkins W-Test for normality. The results of the continuous variables will be described as median (max-min) or mean+/- SD according to distribuition. The categorical variables will be described as tables of absolute and relative frequencies, and the comparisons between the groups of subjects (according to the dose of capsaicin) will be carried out with chi-square tests. To compare the variables studied between the groups of subjects (according to the different doses of capsaicin), Mann-Whitney U-Test/independent samples Student´s T-Test will be used appropriately. For comparisons of the baseline state with the changes recorded over time, various Wilcoxon signed-rank tests will be performed.The relationship between pungency ratings and MV response will be evaluated by Spearman's rho test. The level of statistical significance will be set at 0.05.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• Mexico
  • Aguascalientes, Mexico, 20259
    • Centenario Hospital Miguel Hidalgo

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Signed Informed Consent Form
• Previous diagnosis and stable condition of one of the following:

Diabetes Mellitus Hypertension Dyslipidemia Chronic Obstructive Pulmonary Disease

Exclusion Criteria:

• History of alergy or hypersensibility to dietary capsaicin
• Previous diagnosis of stroke
• Chronic use of cholinergic/anticholinergic drugs
• Chronic use of sympathomimetic drugs
• Chronic use of serotonergic drugs
• Chronic use of dopaminergic drugs

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Capsaicin .66μMol/ml; Group receiving .66μMol/ml	Drug: Capsaicin; Patients will receive a fixed dose of capsaicin; Other Names: 8-Methyl-N-vanillyl-trans-6-nonenamide
Experimental: Capsaicin .99μMol/ml; Group receiving .99μMol/ml	Drug: Capsaicin; Patients will receive a fixed dose of capsaicin; Other Names: 8-Methyl-N-vanillyl-trans-6-nonenamide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean velocity	The Mean velocity in the Middle Cerebral Artery	20 minutes
Pulsatility Index	A calculated flow parameter in ultrasound, derived from the maximum, minimum, and mean Doppler frequency shifts during a defined cardiac cycle.	20 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean arterial pressure (MAP)	The average arterial pressure throughout one cardiac cycle, systole, and diastole.	20 minutes
Cerebral Blood Flow index	The result of the following formula: CBFi = (MAP * 10) / 1.47^Pulsatility Index.	20 minutes

Collaborators and Investigators

• Sponsor: Instituto Mexicano del Seguro Social
• Collaborators: Centenario Hospital Miguel Hidalgo
• Investigators: Principal Investigator: Juan M Marquez-Romero, MD, MSc, Unidad de Medicina de Alta Especialidad, Torre Medica CMQ

Study record dates

Study Major Dates

• Study Start (Actual): September 20, 2022
• Primary Completion (Actual): September 30, 2022
• Study Completion (Actual): February 28, 2023

Study Registration Dates

• First Submitted: September 13, 2022
• First Submitted That Met QC Criteria: September 13, 2022
• First Posted (Actual): September 16, 2022

Study Record Updates

• Last Update Posted (Actual): March 14, 2023
• Last Update Submitted That Met QC Criteria: March 11, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: capsaicin; cerebal perfusion
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Cerebrovascular Disorders; Physiological Effects of Drugs; Peripheral Nervous System Agents; Sensory System Agents; Dermatologic Agents; Antipruritics; Capsaicin
• Other Study ID Numbers: 2022-E-20

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data will be shared with any qualified investigator upon request to the PI after signing a data use agreement.
• IPD Sharing Time Frame: 6 months
• IPD Sharing Access Criteria: Any qualified investigator in the field
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No