Validating a New Non-invasive Approach to Testing Lidocaine Effectiveness

PhenoSolve

Status and phase: Completed; Early Phase 1

Conditions: ADHD; Controls

Treatments: Drug: Lidocaine gel; Drug: Placebo; Drug: Injected lidocaine

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03680885

2018-271

Details and patient eligibility

About

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

Full description

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.

Enrollment: 20 patients

Sex: All

Ages: 18 to 49 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Health Services Research

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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20 participants in 2 patient groups

Reports getting numb at dentist

Active Comparator group

Description:

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.

Treatment:

Drug: Lidocaine gel

Drug: Injected lidocaine

Drug: Placebo

Reports trouble getting numb at dentist

Active Comparator group

Description:

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.

Treatment:

Drug: Lidocaine gel

Drug: Injected lidocaine

Drug: Placebo