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PruritusPhase 2NCT03096444

Antipruritic Effect of Topical Ketamine, Amitriptyline, and Lidocaine

A Phase 2 study testing Ketamine Hydrochloride, Amitriptyline Hydrochloride and Lidocaine Hydrochloride in people with Pruritus, run by Gil Yosipovitch at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 to 50 yearsHealthy volunteers can take part
Conditions the study is for
Pruritus
What is being tested?
Ketamine Hydrochloride, Amitriptyline Hydrochloride and Lidocaine Hydrochloride
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
13 participants
Where
1 siteUnited States
Study dates
23 May 2017to 21 Jul 2017
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 50 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • Healthy subjects (absence of disease) between 18 and 50 years of age.
  • Must be in general good health with no disease or physical conditions that would impair evaluation of itch and pain perception.
  • No history of chronic itch or pain.
  • Must abstain from the use of any systemic or topical anti-histamine, steroid, or pain relief medications 48 hours prior to the study visits.
  • Must abstain from the use of moisturizers on the arms the day of study visit.

Who cannot join

  • Individuals under 18 or over 50 years of age.
  • Inability to complete the required measures.
  • The presence of an itchy skin disease or a painful condition.
  • Diagnosis of diseased that would affect itch or pain perception (e.g. neuropathies).
  • Currently enrolled in any investigational study in which the subject is receiving any type of drug, biological, or non-drug therapy.
  • Use of oral, topical analgesics, or other medications known to interfere with itch or pain perception 48 hours prior to the study visits (e.g. antihistamines, anesthetics, anti-inflammatories, opioids, neuroleptics, etc.).
Show all 10Show fewer
  • Use of emollients on the volar aspects of the forearms arms on the day of the study visit.
  • Use of anti-depressants, anti-psychotics, and illicit drugs.
  • Known history of neuropathy, uremia, uncontrolled thyroid disease, and diabetes mellitus.
  • Known history of anaphylactic shock, or allergy to cowhage and/or known adverse reactions to lidocaine (or other local anesthetics of the amide type), ketamine or amitriptyline.

Trial locations and contacts

1 site in 1 country.

United States1 site
  • University of Miami

    Miami, Florida, 33136

Other trials in United States

About this study

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.

Read the detailed description

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.

Conditions
Pruritus
Being tested
Ketamine Hydrochloride, Amitriptyline Hydrochloride, Lidocaine Hydrochloride, Ketamine hydrochloride, Amitriptyline hydrochloride, and Lidocaine hydrochloride, Lipoderm Cream
Medical subject headings
Pruritus

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Ketamine HydrochlorideDrug

    Also called Topical ketamine

    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.

  • Amitriptyline HydrochlorideDrug

    Also called Topical amitriptyline

    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.

  • Lidocaine HydrochlorideDrug

    Also called Topical lidocaine

    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.

  • Ketamine hydrochloride, Amitriptyline hydrochloride, and Lidocaine hydrochlorideCombination product

    Also called Topical KeAmLi combo

    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.

  • Lipoderm CreamDrug

    Also called Topical vehicle

    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.

Study groups in NCT03096444
Study groupRoleWhat they receive
Topical KeAmLi comboExperimentalTopical 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.
Receives: Combination Product: Ketamine hydrochloride, Amitriptyline hydrochloride, and Lidocaine hydrochloride
Topical ketamineExperimentalTopical 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.
Receives: Drug: Ketamine Hydrochloride
Topical amitriptylineExperimentalTopical 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.
Receives: Drug: Amitriptyline Hydrochloride
Topical lidocaineExperimentalTopical 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.
Receives: Drug: Lidocaine Hydrochloride
Topical vehiclePlacebo comparatorTopical 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.
Receives: Drug: Lipoderm Cream

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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".

    Measured: 10 minutes

Secondary outcomes (2)
  1. 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.

    Measured: 3 minutes

  2. 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.

    Measured: 5 minutes

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Mar 2017
  2. Study start23 May 2017
  3. Primary completion19 Jul 2017
  4. Study completion21 Jul 2017

Why it stopped: Efficacy was not seen after interim analysis

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Model description
The antipruritic effect of 4 topical treatments and 1 vehicle treatment will be explored in each subject. Study visit 1 will consist of testing 3 topical formulations, and study visit 2 will test the remaining 2 topical formulations in each subject.
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
13 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03096444
Sponsor's protocol ID
20170087
Status last verified
Apr 2019
First submitted
16 Mar 2017
Last updated
2 Jul 2019
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Weisshaar E, Gieler U, Kupfer J, Furue M, Saeki H, Yosipovitch G; International Forum on the Study of Itch. Questionnaires to assess chronic itch: a consensus paper of the special interest group of the International Forum on the Study of Itch. Acta Derm Venereol. 2012 Sep;92(5):493-6. doi: 10.2340/00015555-1402.

    PubMed 22688895
  • Matterne U, Apfelbacher CJ, Vogelgsang L, Loerbroks A, Weisshaar E. Incidence and determinants of chronic pruritus: a population-based cohort study. Acta Derm Venereol. 2013 Sep 4;93(5):532-7. doi: 10.2340/00015555-1572.

    PubMed 23450324
  • Matterne U, Apfelbacher CJ, Loerbroks A, Schwarzer T, Buttner M, Ofenloch R, Diepgen TL, Weisshaar E. Prevalence, correlates and characteristics of chronic pruritus: a population-based cross-sectional study. Acta Derm Venereol. 2011 Oct;91(6):674-9. doi: 10.2340/00015555-1159.

    PubMed 21879245
  • Leknes SG, Bantick S, Willis CM, Wilkinson JD, Wise RG, Tracey I. Itch and motivation to scratch: an investigation of the central and peripheral correlates of allergen- and histamine-induced itch in humans. J Neurophysiol. 2007 Jan;97(1):415-22. doi: 10.1152/jn.00070.2006. Epub 2006 Aug 16.

    PubMed 16914620
  • Wahlgren CF. Itch and atopic dermatitis: an overview. J Dermatol. 1999 Nov;26(11):770-9. doi: 10.1111/j.1346-8138.1999.tb02090.x.

    PubMed 10635621
  • Brenaut E, Garlantezec R, Talour K, Misery L. Itch characteristics in five dermatoses: non-atopic eczema, atopic dermatitis, urticaria, psoriasis and scabies. Acta Derm Venereol. 2013 Sep 4;93(5):573-4. doi: 10.2340/00015555-1599. No abstract available.

    PubMed 23722181
  • Carroll CL, Balkrishnan R, Feldman SR, Fleischer AB Jr, Manuel JC. The burden of atopic dermatitis: impact on the patient, family, and society. Pediatr Dermatol. 2005 May-Jun;22(3):192-9. doi: 10.1111/j.1525-1470.2005.22303.x.

    PubMed 15916563
  • Patel T, Yosipovitch G. Therapy of pruritus. Expert Opin Pharmacother. 2010 Jul;11(10):1673-82. doi: 10.1517/14656566.2010.484420.

    PubMed 20426711
  • Kopsky DJ, Keppel Hesselink JM, Bhaskar A, Hariton G, Romanenko V, Casale R. Analgesic effects of topical ketamine. Minerva Anestesiol. 2015 Apr;81(4):440-9. Epub 2014 May 22.

    PubMed 24847738
  • Coggeshall RE, Carlton SM. Ultrastructural analysis of NMDA, AMPA, and kainate receptors on unmyelinated and myelinated axons in the periphery. J Comp Neurol. 1998 Feb 2;391(1):78-86. doi: 10.1002/(sici)1096-9861(19980202)391:13.3.co;2-8.

    PubMed 9527543
  • Carlton SM, Coggeshall RE. Inflammation-induced changes in peripheral glutamate receptor populations. Brain Res. 1999 Feb 27;820(1-2):63-70. doi: 10.1016/s0006-8993(98)01328-6.

    PubMed 10023031
  • Davidson EM, Coggeshall RE, Carlton SM. Peripheral NMDA and non-NMDA glutamate receptors contribute to nociceptive behaviors in the rat formalin test. Neuroreport. 1997 Mar 3;8(4):941-6. doi: 10.1097/00001756-199703030-00025.

    PubMed 9141069
  • Mehta AK, Halder S, Khanna N, Tandon OP, Singh UR, Sharma KK. Role of NMDA and opioid receptors in neuropathic pain induced by chronic constriction injury of sciatic nerve in rats. J Basic Clin Physiol Pharmacol. 2012;23(2):49-55. doi: 10.1515/jbcpp-2012-0003.

    PubMed 23091273
  • Zhou S, Bonasera L, Carlton SM. Peripheral administration of NMDA, AMPA or KA results in pain behaviors in rats. Neuroreport. 1996 Mar 22;7(4):895-900. doi: 10.1097/00001756-199603220-00012.

    PubMed 8724668
  • Tandon OP, Mehta AK, Halder S, Khanna N, Sharma KK. Peripheral interaction of opioid and NMDA receptors in inflammatory pain in rats. Indian J Physiol Pharmacol. 2010 Jan-Mar;54(1):21-31.

    PubMed 21046916

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ketamine Hydrochloride, Amitriptyline Hydrochloride and Lidocaine Hydrochloride in people with Pruritus, run by Gil Yosipovitch at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 2 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 2 Jul 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Peak Itch Intensity Between the Vehicle and Active Treatments (Individual and KeAmLi-combo). (time frame: 10 minutes). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03096444, which also lists 50 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2019.

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