A Phase 2 interventional study of Ketamine Hydrochloride and Amitriptyline Hydrochloride in Pruritus, sponsored by Gil Yosipovitch. Terminated at 1 site in United States. Open to participants aged 18 Years to 50 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2019-07-02.
Sponsored by Gil Yosipovitch · Phase 2, Interventional, and Treatment
The purpose of this study is to examine the antipruritic efficacy of topical ketamine, amitriptyline, lidocaine, and a tri-combination of ketamine, amitriptyline and lidocaine (hereafter referred to as "KeAmLi") using non-histaminergic itch provocations in healthy volunteers. The primary outcome is itch reduction (AUC) between the vehicle and active treatment (KeAmLi-combo). Secondary outcomes include modality-specific analgesic properties of the topically applied ketamine, amitriptyline, lidocaine, and KeAmLi-combo to controlled quantitative thermal and mechanical stimuli, which can improve our understanding of the mechanism of action of these substances in the context of topical therapy.
This is a double-blind, vehicle-controlled study to evaluate the antipruritic efficacy of topical ketamine, amitriptyline, lidocaine, and a tri-combination of ketamine, amitriptyline and lidocaine (hereafter referred to as "KeAmLi") using non-histaminergic itch provocations in healthy volunteers. Each participant will be pre-treated with the vehicle and 4 active topical creams, over two study visits (3 treatments on the 1st visit and 2 treatment on the 2nd visit). Each treatment will be applied to the randomized forearm test area for 30 minute, and then sensory testing will be performed. Sensory testing includes thermal and mechanical stimuli, and itch induction using the plant cowhage. These tests will reveal mechanistic information and potential cellular and molecular targets for improved antipruritic and analgesic therapies.
354 studies on the registry are indexed under Pruritus; 74 are open to participants now.
This study's enrollment of 13 is below the median of 60 across 294 interventional studies indexed under Pruritus.
Browse Pruritus studies →This is the only study on the registry with Gil Yosipovitch as lead sponsor.
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Exclusion Criteria:
Topical KeAmLi-combo (ketamine 10%, amitriptyline 5%, and lidocaine 5%) will be applied to one four 4 x 4 cm predefined skin areas on the ventral forearms during one of two study visits. The pre-treatment will occur under topical occlusion for 30 minutes to allow the ointment to be adsorbed. Following this, residual ointment will be removed and sensory testing, strictly within the pretreated area, will commence.
Combination Product: Ketamine hydrochloride, Amitriptyline hydrochloride, and Lidocaine hydrochloride
Topical ketamine 10% will be applied to one four 4 x 4 cm predefined skin areas on the ventral forearms during one of two study visits. The pre-treatment will occur under topical occlusion for 30 minutes to allow the ointment to be adsorbed. Following this, residual ointment will be removed and sensory testing, strictly within the pretreated area, will commence.
Drug: Ketamine Hydrochloride
Topical amitriptyline 5% will be applied to one four 4 x 4 cm predefined skin areas on the ventral forearms during one of two study visits. The pre-treatment will occur under topical occlusion for 30 minutes to allow the ointment to be adsorbed. Following this, residual ointment will be removed and sensory testing, strictly within the pretreated area, will commence.
Drug: Amitriptyline Hydrochloride
Topical lidocaine 5% will be applied to one four 4 x 4 cm predefined skin areas on the ventral forearms during one of two study visits. The pre-treatment will occur under topical occlusion for 30 minutes to allow the ointment to be adsorbed. Following this, residual ointment will be removed and sensory testing, strictly within the pretreated area, will commence.
Drug: Lidocaine Hydrochloride
Topical vehicle (PCCA Lipoderm) will be applied to one four 4 x 4 cm predefined skin areas on the ventral forearms during one of two study visits. The pre-treatment will occur under topical occlusion for 30 minutes to allow the ointment to be adsorbed. Following this, residual ointment will be removed and sensory testing, strictly within the pretreated area, will commence.
Drug: Lipoderm Cream
2g of topical 10% Ketamine will be applied for 30 minutes on one 4x4cm area on the volar forearm in one of two study visits.
Also known as: Topical ketamine
2g of topical 5% Amitriptyline will be applied for 30 minutes on one 4x4cm area on the volar forearm in one of two study visits.
Also known as: Topical amitriptyline
2g of topical 5% Lidocaine will be applied for 30 minutes on one 4x4cm area on the volar forearm in one of two study visits.
Also known as: Topical lidocaine
2g of topical KeAmLi-combo (ketamine 10%, amitriptyline 5%, and lidocaine 5%) will be applied for 30 minutes on one 4x4cm area on the volar forearm in one of two study visits.
Also known as: Topical KeAmLi combo
2g of topical vehicle (Lipoderm) will be applied for 30 minutes on one 4x4cm area on the volar forearm in one of two study visits.
Also known as: Topical vehicle
Peak Itch Intensity Between the Vehicle and Active Treatments (Individual and KeAmLi-combo).
Peak itch intensity between the vehicle and 4 other active treatments (individual ketamine, amitriptyline, or lidocaine, and KeAmLi-combo). Itch intensity was measured on a 100mm scale visual analog scale for 10 minutes. 0 was weighted with "no itch" and 100 was weighted with "most itch imaginable".
Time frame: 10 minutes
Thermal Threshold Detection (Warmth and Heat Pain)
Two standardized quantitative sensory tests are performed to measure warmth detection threshold (assesses the threshold of which warmth sensation is first detected) and heat pain threshold (assesses the threshold at which heat pain sensation is first detected). Measured in change in celsius.
Time frame: 3 minutes
Mechanical Thresholds (Mechanical Detection and Pain).
Assess mechanical detection and pain thresholds using von Frey filaments stimulators (measured in force mN) to calculate the final threshold as the geometric mean of five series of ascending and descending stimuli.
Time frame: 5 minutes
| Milestone | Topical KeAmLi Combo/Ketamine/Amitriptyline/Lidocaine/Vehicle |
|---|---|
| Started | 13 |
| Completed | 13 |
| Not completed | 0 |
Peak itch intensity between the vehicle and 4 other active treatments (individual ketamine, amitriptyline, or lidocaine, and KeAmLi-combo). Itch intensity was measured on a 100mm scale visual analog scale for 10 minutes. 0 was weighted with "no itch" and 100 was weighted with "most itch imaginable".
| Intensity score | Topical KeAmLi Combo | Topical Ketamine | Topical Amitriptyline | Topical Lidocaine | Topical Vehicle |
|---|---|---|---|---|---|
| Peak Itch Intensity Between the Vehicle and Active Treatments (Individual and KeAmLi-combo). | 62.7 ± 29.00397851 | 63.1 ± 30.11218341 | 69.2 ± 29.52725816 | 65.8 ± 33.80866222 | 61.9 ± 33.95207784 |
Two standardized quantitative sensory tests are performed to measure warmth detection threshold (assesses the threshold of which warmth sensation is first detected) and heat pain threshold (assesses the threshold at which heat pain sensation is first detected). Measured in change in celsius.
| Degrees celsius | Topical KeAmLi Combo | Topical Ketamine | Topical Amitriptyline | Topical Lidocaine | Topical Vehicle |
|---|---|---|---|---|---|
| Warm Detection Threshold | 33.6 ± 0.303939003 | 34.0 ± 1.10853976 | 33.9 ± 0.649150223 | 33.7 ± 0.389004867 | 33.8 ± 0.577436619 |
| Heat Pain Threshold | 39.8 ± 2.401845207 | 40.0 ± 2.2098072 | 40.0 ± 2.80388162 | 39.4 ± 2.305045253 | 39.7 ± 2.227588606 |
Assess mechanical detection and pain thresholds using von Frey filaments stimulators (measured in force mN) to calculate the final threshold as the geometric mean of five series of ascending and descending stimuli.
| mN | Topical KeAmLi Combo | Topical Ketamine | Topical Amitriptyline | Topical Lidocaine | Topical Vehicle |
|---|---|---|---|---|---|
| Mechanical Detection Threshold | 3.519376956 ± 0.122225324 | 3.464204768 ± 0.16205246 | 3.573423965 ± 0.141531726 | 3.546037659 ± 0.157416303 | 3.525692637 ± 0.169487169 |
| Mechanical Pain Threshold | 152.3293608 ± 90.32609423 | 135.9 ± 121.5234567 | 152.4768146 ± 114.1149716 | 126.9 ± 106.9414678 | 148.7138273 ± 104.3418768 |
Collected over Data was collect for 1 week from the time of treatment.. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Topical KeAmLi Combo | 0/13 (0%) | 0/13 (0%) | 0/13 (0%) |
| Topical Ketamine | 0/13 (0%) | 0/13 (0%) | 0/13 (0%) |
| Topical Amitriptyline | 0/13 (0%) | 0/13 (0%) | 0/13 (0%) |
| Topical Lidocaine | 0/13 (0%) | 0/13 (0%) | 0/13 (0%) |
| Topical Vehicle | 0/13 (0%) | 0/13 (0%) | 0/13 (0%) |
All subjects received 5 topical cream treatments
| Age, Categorical(Participants) | Topical KeAmLi Combo/Ketamine/Amitriptyline/Lidocaine/Vehicle |
|---|---|
| <=18 years | 0 |
| Between 18 and 65 years | 13 |
| >=65 years | 0 |
| Sex: Female, Male(Participants) | Topical KeAmLi Combo/Ketamine/Amitriptyline/Lidocaine/Vehicle |
|---|---|
| Female | 9 |
| Male | 4 |
| Ethnicity (NIH/OMB)(Participants) | Topical KeAmLi Combo/Ketamine/Amitriptyline/Lidocaine/Vehicle |
|---|---|
| Hispanic or Latino | 5 |
| Not Hispanic or Latino | 8 |
| Unknown or Not Reported | 0 |
| Race (NIH/OMB)(Participants) | Topical KeAmLi Combo/Ketamine/Amitriptyline/Lidocaine/Vehicle |
|---|---|
| American Indian or Alaska Native | 0 |
| Asian | 3 |
| Native Hawaiian or Other Pacific Islander | 0 |
| Black or African American | 1 |
| White | 9 |
| More than one race | 0 |
| Unknown or Not Reported | 0 |
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