The Effect of Halophyte-based Cream on Pain and Itch

Overview

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.

Full Title of Study: “Effects of Halophyte-based Cream Skin Application in a Human Experimental Model of Pain and Itch”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Basic Science
    • Masking: Single (Participant)
  • Study Primary Completion Date: November 1, 2021

Detailed 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.

Interventions

  • 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 4×4 cm squared area.
  • Other: 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 4×4 cm squared area.
  • Other: Vehicle cream 24 hours
    • A 2 gram amount of vehicle cream will be applied under occlusion (TegaDerm tape) in a 4×4 cm squared area.
  • Other: Vehicle cream 48 hours
    • A 2 gram amount of vehicle cream will be applied under occlusion (TegaDerm tape) in a 4×4 cm squared area.
  • Other: 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.
  • Other: 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.

Arms, Groups and Cohorts

  • Active Comparator: Halophites-based cream 24 hours
    • A 2 gram amount of Halophites-based cream will be applied under occlusion (TegaDerm tape) in a 4×4 cm squared area.
  • Active Comparator: Halophites-based cream 48 hours
    • A 2 gram amount of Halophites-based cream will be applied under occlusion (TegaDerm tape) in a 4×4 cm squared area.

Clinical Trial Outcome Measures

Primary Measures

  • Superficial blood perfusion
    • Time Frame: Day 0
    • Superficial blood perfusion is measured by a Speckle contrast imager (FLPI, Moor Instruments, England).
  • Superficial blood perfusion
    • Time Frame: 24 hours after cream application
    • Superficial blood perfusion is measured by a Speckle contrast imager (FLPI, Moor Instruments, England).
  • Superficial blood perfusion
    • Time Frame: 48 hours after cream application
    • Superficial blood perfusion is measured by a Speckle contrast imager (FLPI, Moor Instruments, England).
  • Itch intensity
    • Time Frame: Day 0
    • 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
  • Itch intensity
    • Time Frame: 24 hours after cream application
    • 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
  • Itch intensity
    • Time Frame: 48 hours after cream application
    • 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
  • Pain intensity
    • Time Frame: Day 0
    • 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
  • Pain intensity
    • Time Frame: 24 hours after cream application
    • 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
  • Pain intensity
    • Time Frame: 48 hours after cream application
    • 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
  • Measuring Alloknesis
    • Time Frame: Day 0
    • Alloknesis is measured by using mildly pruritic, non-painful von Frey nylon filaments of a predetermined intensity (generally 5-30 miliNewton of force).
  • Measuring Alloknesis
    • Time Frame: 24 hours after cream application
    • Alloknesis is measured by using mildly pruritic, non-painful von Frey nylon filaments of a predetermined intensity (generally 5-30 miliNewton of force).
  • Measuring Alloknesis
    • Time Frame: 48 hours after cream application
    • Alloknesis is measured by using mildly pruritic, non-painful von Frey nylon filaments of a predetermined intensity (generally 5-30 miliNewton of force).
  • Trans-epidermal Water Loss (TEWL)
    • Time Frame: Day 0
    • TEWL is a non-invasive and pain free measuring technique in which a 2×2 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.
  • Trans-epidermal Water Loss (TEWL)
    • Time Frame: 24 hours after cream application
    • TEWL is a non-invasive and pain free measuring technique in which a 2×2 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.
  • Trans-epidermal Water Loss (TEWL)
    • Time Frame: 48 hours after cream application
    • TEWL is a non-invasive and pain free measuring technique in which a 2×2 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.

Secondary Measures

  • Measurement of Warm Detection Thresholds (WDT)
    • Time Frame: Day 0
    • The tests for thermal sensation will all be performed using a PATHWAY ATS (Medoc Ltd, Israel) thermal sensory testing device. A thermode stimulator of 3×3 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.
  • Measurement of Warm Detection Thresholds (WDT)
    • Time Frame: 24 hours after cream application
    • The tests for thermal sensation will all be performed using a PATHWAY ATS (Medoc Ltd, Israel) thermal sensory testing device. A thermode stimulator of 3×3 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.
  • Measurement of Warm Detection Thresholds (WDT)
    • Time Frame: 48 hours after cream application
    • The tests for thermal sensation will all be performed using a PATHWAY ATS (Medoc Ltd, Israel) thermal sensory testing device. A thermode stimulator of 3×3 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.
  • Measurement of Cold Detection Thresholds (CDT)
    • Time Frame: Day 0
    • The tests for thermal sensation will all be performed using a PATHWAY ATS (Medoc Ltd, Israel) thermal sensory testing device. A thermode stimulator of 3×3 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.
  • Measurement of Cold Detection Thresholds (CDT)
    • Time Frame: 24 hours after cream application
    • The tests for thermal sensation will all be performed using a PATHWAY ATS (Medoc Ltd, Israel) thermal sensory testing device. A thermode stimulator of 3×3 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.
  • Measurement of Cold Detection Thresholds (CDT)
    • Time Frame: 48 hours after cream application
    • The tests for thermal sensation will all be performed using a PATHWAY ATS (Medoc Ltd, Israel) thermal sensory testing device. A thermode stimulator of 3×3 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.
  • Measurement of Heat Pain Thresholds (HPT)
    • Time Frame: Day 0
    • 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.
  • Measurement of Heat Pain Thresholds (HPT)
    • Time Frame: 24 hours after cream application
    • 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.
  • Measurement of Heat Pain Thresholds (HPT)
    • Time Frame: 48 hours after cream application
    • 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.
  • Measurement of Cold Pain Thresholds (CPT)
    • Time Frame: Day 0
    • The tests for thermal sensation will all be performed using a PATHWAY ATS (Medoc Ltd, Israel) thermal sensory testing device. A thermode stimulator of 3×3 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.
  • Measurement of Cold Pain Thresholds (CPT)
    • Time Frame: 24 hours after cream application
    • The tests for thermal sensation will all be performed using a PATHWAY ATS (Medoc Ltd, Israel) thermal sensory testing device. A thermode stimulator of 3×3 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.
  • Measurement of Cold Pain Thresholds (CPT)
    • Time Frame: 48 hours after cream application
    • The tests for thermal sensation will all be performed using a PATHWAY ATS (Medoc Ltd, Israel) thermal sensory testing device. A thermode stimulator of 3×3 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.
  • Measurement of Pain to Supra-threshold Heat Stimuli:
    • Time Frame: Day 0
    • 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 .
  • Measurement of Pain to Supra-threshold Heat Stimuli:
    • Time Frame: 24 hours after cream application
    • 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 .
  • Measurement of Pain to Supra-threshold Heat Stimuli:
    • Time Frame: 48 hours after cream application
    • 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 .
  • Measurement of Mechanical Pain Thresholds (MPT)
    • Time Frame: Day 0
    • 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.
  • Measurement of Mechanical Pain Thresholds (MPT)
    • Time Frame: 24 hours after cream application
    • 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.
  • Measurement of Mechanical Pain Thresholds (MPT)
    • Time Frame: 48 hours after cream application
    • 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.
  • Measurement of Mechanical Pain Sensitivity (MPS)
    • Time Frame: Day 0
    • 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.
  • Measurement of Mechanical Pain Sensitivity (MPS)
    • Time Frame: 24 hours after cream application
    • 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.
  • Measurement of Mechanical Pain Sensitivity (MPS)
    • Time Frame: 48 hours after cream application
    • 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.

Participating in This Clinical Trial

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)

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 60 Years

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

  • Lead Sponsor
    • Aalborg University
  • Provider of Information About this Clinical Study
    • Principal Investigator: Rocco Giordano, Principal Investigator – Aalborg University

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