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 |
|