Validating a New Non-invasive Approach to Testing Lidocaine Effectiveness

Study Overview
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Brief Summary
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This work will assess the reliability of a simple painless test for the effectiveness of the commonly used local anesthetic lidocaine

Detailed Description
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In prior tests with a convenience sample, subjects who reported that they had no trouble getting numb at the dentist, also got numb with lidocaine gel on the surface of the tongue. That numbness prevented them from being able to taste any flavor until the numbness had worn off. Subjects who reported having trouble getting numb at the dentist, could still taste flavors after the application of lidocaine. This work will assess the reliability of a taste-based approach for creating a non-invasive way to test lidocaine effectiveness. The controlled trial will assess the ability of lidocaine oral gel to block taste (e.g., sweet) in 20 adults (ages 18-49) half with history of trouble getting numb at the dentist (Arm 2) and half with no trouble (Arm 1). To determine reproducibility, the taste-based test will be done 4 times on different days, twice with lidocaine and twice with a placebo, with randomization and double-blinding. These repeated results will be compared to a fifth assessment, against the gold standard of injection of lidocaine, assessed using a dental probe. On each of four separate visits, in randomized order, the subject will be tested with tastants to the tongue twice after application of a lidocaine gel to the tongue and twice with a placebo gel. After a wait of two-minutes, the three tastants will be tested. The subject is blinded to the taste and the identity of the gel, which have been compounded to look the same. On the fifth (last) visit, the subject will get an oral injection of lidocaine and the numbness assessed. The results across the five tests will then be analyzed. We are testing in separate studies NCT 03563573 and NCT 03676725 the prevalence of lidocaine ineffectiveness in those with Attention Deficit Hyperactivity Disorder (ADHD) and in the general population without ADHD. We believe the prevalence will be higher in ADHD. As a result, in this evaluation we have one Arm gets numb at the dentist where exclusion criteria includes ADHD and a second Arm has trouble getting numb at the dentist that does not have that exclusion.

Official Title
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Reliability Testing of a Non-invasive, Pain-free, Taste-based Assessment Approach to Lidocaine Effectiveness

Conditions
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ADHD, Controls

Intervention / Treatment
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* Drug: Lidocaine gel
* Drug: Placebo
* Drug: Injected lidocaine


Participation Criteria
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Eligibility Criteria
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Arm 1 Eligibility Inclusion Criteria: - Report get numb at dentist Exclusion Criteria: ADHD, ADD, and other inattention disorders Known adverse reactions to lidocaine; Epilepsy IQ <80 Severe head trauma Birth weight <2270 grams Severe autism Generalized anxiety disorders (but dental-specific anxiety will not be an exclusion because many of these individuals may be ones with anxiety because of painful dental experiences with lidocaine ineffectiveness) Mouth sores Ehlers Danlos syndrome Red hair Current pregnancy Treatment currently with potassium or potassium-elevating drugs such as renin-angiotensin-aldosterone blockers Angiotensin Converting Enzyme Inhibitors Alacepril (not available in US) Benazepril (Lotensin) Captopril (trade name Capoten) Cilazapril (Inhibace) Delapril (not available in US) Enalapril (Vasotec/Renitec) Fosinopril (Fositen/Monopril) Imidapril (Tanatril) Lisinopril (Listril/Lopril/Novatec/Prinivil/Zestril) Moexipril (Univasc) Perindopril (Coversyl/Aceon/Perindo) Quinapril (Accupril) Ramipril (Altace/Prilace/Ramace/Ramiwin/Triatec/Tritace) Spirapril (Renormax) Temocapril (not available in US) Teprotide (but not active by oral administration and not used in US) Trandolapril (Mavik/Odrik/Gopten) Zofenopril Angiotensin receptor blockers Azilsartan (Edarbi) Candesartan (Atacand) Eprosartan (Teveten) Fimasartan (Kanarb) Irbesartan (Avapro) Losartan (Cozaar) Olmesartan (Benicar/Olmetec) Telmisartan (Micardis) Valsartan (Diovan) Aldosterone antagonists Spironolactone (Aldactone) Eplerenone (Inspra) Renin inhibitors - Aliskiren (Tekturna, Rasilez) Other potassium elevating agents Antibiotics, including penicillin G and trimethoprim Azole antifungals Beta-blockers Herbal supplements, including milkweed, lily of the valley, Siberian ginseng, Hawthorn berries Heparin Nonsteroidal anti-inflammatory medications (NSAIDs) Oral contraceptives containing drospirenone Arm 2 Eligibility Inclusion Criteria: - Report trouble getting numb at dentist Exclusion Criteria: Known adverse reactions to lidocaine; Epilepsy IQ <80 Severe head trauma Birth weight <2270 grams Severe autism Generalized anxiety disorders (but dental-specific anxiety will not be an exclusion because many of these individuals may be ones with anxiety because of painful dental experiences with lidocaine ineffectiveness) Mouth sores Ehlers Danlos syndrome Red hair Current pregnancy Treatment currently with potassium or potassium-elevating drugs such as renin-angiotensin-aldosterone blockers Angiotensin Converting Enzyme Inhibitors Alacepril (not available in US) Benazepril (Lotensin) Captopril (trade name Capoten) Cilazapril (Inhibace) Delapril (not available in US) Enalapril (Vasotec/Renitec) Fosinopril (Fositen/Monopril) Imidapril (Tanatril) Lisinopril (Listril/Lopril/Novatec/Prinivil/Zestril) Moexipril (Univasc) Perindopril (Coversyl/Aceon/Perindo) Quinapril (Accupril) Ramipril (Altace/Prilace/Ramace/Ramiwin/Triatec/Tritace) Spirapril (Renormax) Temocapril (not available in US) Teprotide (but not active by oral administration and not used in US) Trandolapril (Mavik/Odrik/Gopten) Zofenopril Angiotensin receptor blockers Azilsartan (Edarbi) Candesartan (Atacand) Eprosartan (Teveten) Fimasartan (Kanarb) Irbesartan (Avapro) Losartan (Cozaar) Olmesartan (Benicar/Olmetec) Telmisartan (Micardis) Valsartan (Diovan) Aldosterone antagonists Spironolactone (Aldactone) Eplerenone (Inspra) Renin inhibitors - Aliskiren (Tekturna, Rasilez) Other potassium elevating agents Antibiotics, including penicillin G and trimethoprim Azole antifungals Beta-blockers Herbal supplements, including milkweed, lily of the valley, Siberian ginseng, Hawthorn berries Heparin Nonsteroidal anti-inflammatory medications (NSAIDs) Oral contraceptives containing drospirenone

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 49 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Health Services Research
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Half the subjects will have a self-reported history of lidocaine working for them (effective) and half will have a history of difficulty getting numb (ineffective).
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Reports getting numb at dentist<br>Subjects will be tested twice with lidocaine gel, twice with a Placebo and once with Injected Lidocaine to assess effectiveness of lidocaine. Each assessment will be on a different day. | Drug: Lidocaine gel<br>* Lidocaine gel 5%, PEG with FD&C Blue No.1 (Brilliant Blue FCF)<br>* Other names: Intervention;Drug: Placebo<br>* PEG with FD&C Blue No.1 (Brilliant Blue FCF)<br>* Other names: Control gel;Drug: Injected lidocaine<br>* Standard FDA-approved dental injectable lidocaine<br>* Other names: Current practice;|
| Active Comparator: Reports trouble getting numb at dentist<br>Subjects will be tested twice with lidocaine gel, twice with a Placebo and once with Injected Lidocaine to assess effectiveness of lidocaine. Each assessment will be on a different day. | Drug: Lidocaine gel<br>* Lidocaine gel 5%, PEG with FD&C Blue No.1 (Brilliant Blue FCF)<br>* Other names: Intervention;Drug: Placebo<br>* PEG with FD&C Blue No.1 (Brilliant Blue FCF)<br>* Other names: Control gel;Drug: Injected lidocaine<br>* Standard FDA-approved dental injectable lidocaine<br>* Other names: Current practice;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Taste sensation after lidocaine or placebo | The subject is blinded to the tastant and gel identities. The 3 tastants are tested in randomized order. After application of lidocaine gel or placebo to the tongue, and a wait of 2 minutes, the subject's tongue is rubbed with a swab that has been wet with the tastant on the subject's tongue. The subject is asked to identify the taste (e.g., sweet). Then, on a 5-point scale (0-4, ranging from none to very intense) they are asked to rate the intensity of the taste. The process is repeated for each of the three tastants. The consistency of the subject responses over the 4 sessions will be analyzed. | 4 visits each of 30 minutes within weeks of one another, average  1 month total | 
| Ability to feel pressure and discomfort after injection of lidocaine into the cheek | Inject lidocaine as would be done in a dental visit, assess numbness to pressure and discomfort using the Baker Wong FACES scale (0-10) scale of discomfort, ranging from none to intense pain. The effectiveness of lidocaine will be assessed, and then the results compared to Outcome 1. | 1 visit of 30 minutes after other 4 visits, average  1 month total | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lidocaine ineffectiveness, ADHD, ADD