The Effect of Halophyte-based Cream on Pain and Itch

Pain, Acute Clinical Trial

Official title:

Effects of Halophyte-based Cream Skin Application in a Human Experimental Model of Pain and Itch

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04635254
• Other study ID #: N-20200072
• Status: Completed
• Phase: N/A
• Start date: November 12, 2020
• Est. completion date: December 1, 2021

Study information

• Verified date: January 2022
• Source: Aalborg University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

In this study the investigators wish to investigate whether halophyte-based cream applied to the skin can reduce itch applied by means of small needles from the plant mucuna pruriens (also called cowhage) or by histamine (an itch-evoking substance formed in the human body). Further, the investigators wishes to investigate whether long-term application of halophyte-based cream has a pain-relieving effect on heat/cold and pinprick stimulations.

Description:

Salt-tolerant plants (also called halophytes) can grow in saline soil or directly in salt water (e.g. along coasts). For centuries, these plants have been used in folk medicine, and among other things they are believed to have pain-relieving and anti-inflammatory effect. Even though experiments have already investigated halophytes as a pain relieving substance, the mechanisms in relation to pain and/or itch are still unknown. Therefore, the investigators wish to investigate whether halophyte-based cream applied to the skin can reduce itch applied by means of small needles from the plant mucuna pruriens (also called cowhage) or by histamine (an itch-evoking substance formed in the human body). Further, the investigators wishes to investigate whether long-term application of halophyte-based cream has a pain-relieving effect on heat/cold and pinprick stimulations.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: December 1, 2021
• Est. primary completion date: November 1, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

• Healthy men and women
• 18-60 years
• Speak and understand English

Exclusion Criteria:

• Pregnancy or lactation
• Drug addiction defined as any use of cannabis, opioids or other drugs
• Previous or current neurologic, musculoskeletal or mental illnesses that may affect the results (e.g. neuropathy, muscular pain in the upper extremities, etc.)
• Lack of ability to cooperate
• Current use of medications that may affect the trial such as antihistamine medications or pain killers
• Skin diseases
• Consumption of alcohol or painkillers 24 hours before the study days and between these
• Acute or chronic pain
• Participation in other trials within 1 week of study entry (4 weeks in the case of pharmaceutical trials)

Related Conditions & MeSH terms

• Acute Pain
• Itch
• Pain, Acute

Intervention

Other:
• Halophites-based cream 24 hours
The concentration of active aqueous extract will be in the range of 2% to 30% (v/v) by cold emulsification. A 2 gram amount of Halophytes-based cream will be applied under occlusion (TegaDerm tape) in a 4x4 cm squared area.
• Halophites-based cream 48 hours
The concentration of active aqueous extract will be in the range of 2% to 30% (v/v) by cold emulsification. A 2 gram amount of Halophytes-based cream will be applied under occlusion (TegaDerm tape) in a 4x4 cm squared area.
• Vehicle cream 24 hours
A 2 gram amount of vehicle cream will be applied under occlusion (TegaDerm tape) in a 4x4 cm squared area.
• Vehicle cream 48 hours
A 2 gram amount of vehicle cream will be applied under occlusion (TegaDerm tape) in a 4x4 cm squared area.
• Histamine 1%
To deliver histamine, standard allergy skin prick test (SPT) lancets are applied. The lancets have a 1 mm shouldered tip adapt to introduce a small amount of test substance extremely locally and approximately at the dermo-epidermal junction.
• Cowhage
The insertion of cowhage spicule(s) rapidly and consistently produces itch with no or very little flare reaction. This insertion is conducted by forceps using a stereo-microscope, and 30-35 spicules are gently rubbed into a 1 cm diameter skin area.

Locations

Country	Name	City	State
Denmark	Aalborg University	Aalborg

Sponsors (1)

Lead Sponsor	Collaborator
Aalborg University

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Superficial blood perfusion	Superficial blood perfusion is measured by a Speckle contrast imager (FLPI, Moor Instruments, England).	Day 0
Primary	Superficial blood perfusion	Superficial blood perfusion is measured by a Speckle contrast imager (FLPI, Moor Instruments, England).	24 hours after cream application
Primary	Superficial blood perfusion	Superficial blood perfusion is measured by a Speckle contrast imager (FLPI, Moor Instruments, England).	48 hours after cream application
Primary	Itch intensity	The subject will rate the itch sensation on a 100 millimeter Visual Analog Scale from 0 to 100., where 0"indicates no itch and "100" worst itch imaginable	Day 0
Primary	Itch intensity	The subject will rate the itch sensation on a 100 millimeter Visual Analog Scale from 0 to 100., where 0"indicates no itch and "100" worst itch imaginable	24 hours after cream application
Primary	Itch intensity	The subject will rate the itch sensation on a 100 millimeter Visual Analog Scale from 0 to 100., where 0"indicates no itch and "100" worst itch imaginable	48 hours after cream application
Primary	Pain intensity	The subject will rate the pain sensation on a 100 millimeter Visual Analog Scale from 0 to 100., where 0"indicates no pain and "100" worst pain imaginable	Day 0
Primary	Pain intensity	The subject will rate the pain sensation on a 100 millimeter Visual Analog Scale from 0 to 100., where 0"indicates no pain and "100" worst pain imaginable	24 hours after cream application
Primary	Pain intensity	The subject will rate the pain sensation on a 100 millimeter Visual Analog Scale from 0 to 100., where 0"indicates no pain and "100" worst pain imaginable	48 hours after cream application
Primary	Measuring Alloknesis	Alloknesis is measured by using mildly pruritic, non-painful von Frey nylon filaments of a predetermined intensity (generally 5-30 miliNewton of force).	Day 0
Primary	Measuring Alloknesis	Alloknesis is measured by using mildly pruritic, non-painful von Frey nylon filaments of a predetermined intensity (generally 5-30 miliNewton of force).	24 hours after cream application
Primary	Measuring Alloknesis	Alloknesis is measured by using mildly pruritic, non-painful von Frey nylon filaments of a predetermined intensity (generally 5-30 miliNewton of force).	48 hours after cream application
Primary	Trans-epidermal Water Loss (TEWL)	TEWL is a non-invasive and pain free measuring technique in which a 2x2 cm hollow probe with two small humidity gauges and two thermometers is placed lightly on the skin for 10-25 seconds. These collectively establish a precise humidity gradient in a 2 cm vicinity of the skin, representative for the point-loss of water though the epidermis.	Day 0
Primary	Trans-epidermal Water Loss (TEWL)	TEWL is a non-invasive and pain free measuring technique in which a 2x2 cm hollow probe with two small humidity gauges and two thermometers is placed lightly on the skin for 10-25 seconds. These collectively establish a precise humidity gradient in a 2 cm vicinity of the skin, representative for the point-loss of water though the epidermis.	24 hours after cream application
Primary	Trans-epidermal Water Loss (TEWL)	TEWL is a non-invasive and pain free measuring technique in which a 2x2 cm hollow probe with two small humidity gauges and two thermometers is placed lightly on the skin for 10-25 seconds. These collectively establish a precise humidity gradient in a 2 cm vicinity of the skin, representative for the point-loss of water though the epidermis.	48 hours after cream application
Secondary	Measurement of Warm Detection Thresholds (WDT)	The tests for thermal sensation will all be performed using a PATHWAY ATS (Medoc Ltd, Israel) thermal sensory testing device. A thermode stimulator of 3x3 cm will be placed on the treated/placebo areas and kept in place by means of Velcro tape. During the first 8 seconds, the temperature raises 1°C per second from a starting temperature of 32°C until the subject perceives a temperature change (warm sensation) and presses a button that will terminate the measurement and return the temperature to baseline at a rate of 5°C /s. A cut-off temperature of 52°C will be used.	Day 0
Secondary	Measurement of Warm Detection Thresholds (WDT)	The tests for thermal sensation will all be performed using a PATHWAY ATS (Medoc Ltd, Israel) thermal sensory testing device. A thermode stimulator of 3x3 cm will be placed on the treated/placebo areas and kept in place by means of Velcro tape. During the first 8 seconds, the temperature raises 1°C per second from a starting temperature of 32°C until the subject perceives a temperature change (warm sensation) and presses a button that will terminate the measurement and return the temperature to baseline at a rate of 5°C /s. A cut-off temperature of 52°C will be used.	24 hours after cream application
Secondary	Measurement of Warm Detection Thresholds (WDT)	The tests for thermal sensation will all be performed using a PATHWAY ATS (Medoc Ltd, Israel) thermal sensory testing device. A thermode stimulator of 3x3 cm will be placed on the treated/placebo areas and kept in place by means of Velcro tape. During the first 8 seconds, the temperature raises 1°C per second from a starting temperature of 32°C until the subject perceives a temperature change (warm sensation) and presses a button that will terminate the measurement and return the temperature to baseline at a rate of 5°C /s. A cut-off temperature of 52°C will be used.	48 hours after cream application
Secondary	Measurement of Cold Detection Thresholds (CDT)	The tests for thermal sensation will all be performed using a PATHWAY ATS (Medoc Ltd, Israel) thermal sensory testing device. A thermode stimulator of 3x3 cm will be placed on the treated/placebo areas and kept in place by means of Velcro tape. During the first 8 seconds, the temperature decreases 1°C per second from a starting temperature of 32°C until the subject perceives a temperature change (cold sensation) and presses a button that will terminate the measurement and return the temperature to baseline at a rate of 5°C /s. A cut-off temperature of 0°C will be used.	Day 0
Secondary	Measurement of Cold Detection Thresholds (CDT)	The tests for thermal sensation will all be performed using a PATHWAY ATS (Medoc Ltd, Israel) thermal sensory testing device. A thermode stimulator of 3x3 cm will be placed on the treated/placebo areas and kept in place by means of Velcro tape. During the first 8 seconds, the temperature decreases 1°C per second from a starting temperature of 32°C until the subject perceives a temperature change (cold sensation) and presses a button that will terminate the measurement and return the temperature to baseline at a rate of 5°C /s. A cut-off temperature of 0°C will be used.	24 hours after cream application
Secondary	Measurement of Cold Detection Thresholds (CDT)	The tests for thermal sensation will all be performed using a PATHWAY ATS (Medoc Ltd, Israel) thermal sensory testing device. A thermode stimulator of 3x3 cm will be placed on the treated/placebo areas and kept in place by means of Velcro tape. During the first 8 seconds, the temperature decreases 1°C per second from a starting temperature of 32°C until the subject perceives a temperature change (cold sensation) and presses a button that will terminate the measurement and return the temperature to baseline at a rate of 5°C /s. A cut-off temperature of 0°C will be used.	48 hours after cream application
Secondary	Measurement of Heat Pain Thresholds (HPT)	The tests for thermal sensation will all be performed using the same PATHWAY ATS thermal sensory testing device as above. The stimulations are again applied on the treated/placebo areas. During the first 8 seconds, the temperature raises 1°C per second from a starting temperature of 32°C until the subject detects a painful sensation and presses a button that will terminate the measurement and return the temperature to baseline at a rate of 5°C /s. A cut-off temperature of 52°C will be used.	Day 0
Secondary	Measurement of Heat Pain Thresholds (HPT)	The tests for thermal sensation will all be performed using the same PATHWAY ATS thermal sensory testing device as above. The stimulations are again applied on the treated/placebo areas. During the first 8 seconds, the temperature raises 1°C per second from a starting temperature of 32°C until the subject detects a painful sensation and presses a button that will terminate the measurement and return the temperature to baseline at a rate of 5°C /s. A cut-off temperature of 52°C will be used.	24 hours after cream application
Secondary	Measurement of Heat Pain Thresholds (HPT)	The tests for thermal sensation will all be performed using the same PATHWAY ATS thermal sensory testing device as above. The stimulations are again applied on the treated/placebo areas. During the first 8 seconds, the temperature raises 1°C per second from a starting temperature of 32°C until the subject detects a painful sensation and presses a button that will terminate the measurement and return the temperature to baseline at a rate of 5°C /s. A cut-off temperature of 52°C will be used.	48 hours after cream application
Secondary	Measurement of Cold Pain Thresholds (CPT)	The tests for thermal sensation will all be performed using a PATHWAY ATS (Medoc Ltd, Israel) thermal sensory testing device. A thermode stimulator of 3x3 cm will be placed on the treated/placebo areas and kept in place by means of Velcro tape. During the first 8 seconds, the temperature decreases 1°C per second from a starting temperature of 32°C until the subject detects a painful sensation and presses a button that will terminate the measurement and return the temperature to baseline at a rate of 5°C /s. A cut-off temperature of 0°C will be used.	Day 0
Secondary	Measurement of Cold Pain Thresholds (CPT)	The tests for thermal sensation will all be performed using a PATHWAY ATS (Medoc Ltd, Israel) thermal sensory testing device. A thermode stimulator of 3x3 cm will be placed on the treated/placebo areas and kept in place by means of Velcro tape. During the first 8 seconds, the temperature decreases 1°C per second from a starting temperature of 32°C until the subject detects a painful sensation and presses a button that will terminate the measurement and return the temperature to baseline at a rate of 5°C /s. A cut-off temperature of 0°C will be used.	24 hours after cream application
Secondary	Measurement of Cold Pain Thresholds (CPT)	The tests for thermal sensation will all be performed using a PATHWAY ATS (Medoc Ltd, Israel) thermal sensory testing device. A thermode stimulator of 3x3 cm will be placed on the treated/placebo areas and kept in place by means of Velcro tape. During the first 8 seconds, the temperature decreases 1°C per second from a starting temperature of 32°C until the subject detects a painful sensation and presses a button that will terminate the measurement and return the temperature to baseline at a rate of 5°C /s. A cut-off temperature of 0°C will be used.	48 hours after cream application
Secondary	Measurement of Pain to Supra-threshold Heat Stimuli:	Again, the tests will be performed by using the PATHWAY ATS thermal sensory testing device. The subjects will have to rate the pain to three suprathreshold heat pain stimuli (starting and ending at 34°C with an increase and decrease of 5°C and 4 s plateau at 50°C) applied on the treated/placebo areas .	Day 0
Secondary	Measurement of Pain to Supra-threshold Heat Stimuli:	Again, the tests will be performed by using the PATHWAY ATS thermal sensory testing device. The subjects will have to rate the pain to three suprathreshold heat pain stimuli (starting and ending at 34°C with an increase and decrease of 5°C and 4 s plateau at 50°C) applied on the treated/placebo areas .	24 hours after cream application
Secondary	Measurement of Pain to Supra-threshold Heat Stimuli:	Again, the tests will be performed by using the PATHWAY ATS thermal sensory testing device. The subjects will have to rate the pain to three suprathreshold heat pain stimuli (starting and ending at 34°C with an increase and decrease of 5°C and 4 s plateau at 50°C) applied on the treated/placebo areas .	48 hours after cream application
Secondary	Measurement of Mechanical Pain Thresholds (MPT)	This test is performed using a pin-prick set (Aalborg University, Aalborg). The set consists of 8 needles each having a diameter of 0.6 mm and different force applications: 0.8, 1.6, 3.2, 6.4, 12.8, 25.6, 50.1 and 60.0 g. Starting with the lightest, each stimulator is applied at a rate of 2 s on, 2 s off in an ascending order until the first perception of sharpness is reached. The final threshold is the geometric mean of five series of ascending and descending stimuli.	Day 0
Secondary	Measurement of Mechanical Pain Thresholds (MPT)	This test is performed using a pin-prick set (Aalborg University, Aalborg). The set consists of 8 needles each having a diameter of 0.6 mm and different force applications: 0.8, 1.6, 3.2, 6.4, 12.8, 25.6, 50.1 and 60.0 g. Starting with the lightest, each stimulator is applied at a rate of 2 s on, 2 s off in an ascending order until the first perception of sharpness is reached. The final threshold is the geometric mean of five series of ascending and descending stimuli.	24 hours after cream application
Secondary	Measurement of Mechanical Pain Thresholds (MPT)	This test is performed using a pin-prick set (Aalborg University, Aalborg). The set consists of 8 needles each having a diameter of 0.6 mm and different force applications: 0.8, 1.6, 3.2, 6.4, 12.8, 25.6, 50.1 and 60.0 g. Starting with the lightest, each stimulator is applied at a rate of 2 s on, 2 s off in an ascending order until the first perception of sharpness is reached. The final threshold is the geometric mean of five series of ascending and descending stimuli.	48 hours after cream application
Secondary	Measurement of Mechanical Pain Sensitivity (MPS)	This test is performed using the same pin-prick set as for the MPT test. Starting with the lightest, each stimulator is applied at a rate of 2 s on, 2 s off in an ascending order, and the subject will be asked to give a pain rating for each stimulus on a scale from 0-10 (where 0 indicates ''no pain'', and 10 indicates the ''worst imaginable pain''). This procedure will be repeated twice.	Day 0
Secondary	Measurement of Mechanical Pain Sensitivity (MPS)	This test is performed using the same pin-prick set as for the MPT test. Starting with the lightest, each stimulator is applied at a rate of 2 s on, 2 s off in an ascending order, and the subject will be asked to give a pain rating for each stimulus on a scale from 0-10 (where 0 indicates ''no pain'', and 10 indicates the ''worst imaginable pain''). This procedure will be repeated twice.	24 hours after cream application
Secondary	Measurement of Mechanical Pain Sensitivity (MPS)	This test is performed using the same pin-prick set as for the MPT test. Starting with the lightest, each stimulator is applied at a rate of 2 s on, 2 s off in an ascending order, and the subject will be asked to give a pain rating for each stimulus on a scale from 0-10 (where 0 indicates ''no pain'', and 10 indicates the ''worst imaginable pain''). This procedure will be repeated twice.	48 hours after cream application