Motor Tasks + Lidocaine for Dyslexia

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Alberta

Must not be taking: Antiarrhythmics, Anesthetics

Disqualifiers: Severe kidney disease, severe liver disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

60 Participants Needed

Trial Summary

What is the purpose of this trial?

Recent claims report that reading ability is partially dependent on speech production. While the evidence for this claim is compelling, it is not known to what extent, the speech production system contributes to successful reading performance in adult populations with dyslexia. One direct way to determine the influence of speech production feedback on reading performance is to measure reading performance in adults with dyslexia with an added motor component (i.e., sucking on a lollipop, holding a bite bar or numbing their oral mucosa with lidocaine). To adults with and without dyslexia 18 years of age and older (60 in total; 30 in each group), three experimental tasks will be administered under four conditions (no motor task, lollipop, bite bar and lidocaine). The first task asks whether the letter string being presented is a word or a nonword. Secondly, a motor sequencing task will be administered where adults will be asked to label pictures. For all tasks, the accuracy and speed of responses will be measured by a computer while participants wear a fNIRS cap.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are taking certain heart medications (class I or III antiarrhythmic drugs) or another anesthetic containing lidocaine.

Is lidocaine generally safe for use in humans?

Lidocaine is generally safe for adults, but there are risks of toxicity, especially in children, where it can cause serious side effects like seizures. In pregnant rats, high doses showed no harmful effects on the fetus. ^{1 2 3 4 5}

How does the drug lidocaine differ from other treatments for dyslexia?

This treatment is unique because it combines motor tasks with lidocaine, a local anesthetic known for blocking nerve signals, which is not a standard approach for dyslexia. While lidocaine is typically used for pain relief, its potential effects on learning and memory dysfunction, as well as its neuroprotective properties, are being explored in this trial, making it a novel approach for addressing dyslexia. ^{6 7 8 9 10}

Eligibility Criteria

This trial is for adults over 18, both with and without dyslexia, who are proficient in English and weigh at least 110 lbs. It's not suitable for those with a history of reactions to anesthetics, severe kidney or liver disease, certain heart medications, damaged oral mucosa, allergies to lidocaine ingredients like parabens or artificial colors/flavors, other lidocaine treatments, or if pregnant.

Inclusion Criteria

All participants will be healthy and need to be proficient in English as the assessment materials are only available in English.

I weigh at least 110 lbs (50 kg).

Exclusion Criteria

Participant being pregnant or suspecting that she might be pregnant

I am currently using another medication that contains lidocaine or a similar substance.

I have severe kidney disease.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Experimental Tasks

Participants complete three experimental tasks under four conditions (no motor task, lollipop, bite bar, and lidocaine) to measure reading performance and response times.

1 day

1 visit (in-person)

Follow-up

Participants are monitored for any immediate effects post-experiment and data is collected for analysis.

1 day

Treatment Details

Interventions

• Lidocaine

Trial Overview The study tests how motor tasks (like sucking on a lollipop) and numbing the mouth with Lidocaine affect reading unfamiliar words in adults with dyslexia compared to those without. Participants will perform word recognition and picture labeling tasks under different conditions while their brain activity is monitored.

Participant Groups

Group I: Condition Experimental Treatment 1 Intervention

Typical Reader or Individual with Dyslexia

Who Is Running the Clinical Trial?

University of Alberta

Lead Sponsor

Trials

957

Recruited

437,000+

Findings from Research

Viscous lidocaine can pose a high risk of overdose in pediatric patients due to their altered pharmacokinetics, making doses safe for adults potentially toxic for children.

Benzocaine is recommended as a safer alternative for treating painful mouth lesions in children, as it has a lower incidence of side effects, but if lidocaine must be used, clear and specific dosing instructions should be provided to parents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lidocaine overdose: another preventable case? Gonzalez del Rey, J., Wason, S., Druckenbrod, RW.[2019]

A case study of a 5-month-old infant revealed that seizures can occur due to toxicity from oral viscous lidocaine, highlighting a serious risk associated with its use in young children.

Despite previous reports of lidocaine toxicity, many healthcare providers remain unaware of its potential adverse effects, emphasizing the need for increased awareness and caution when prescribing topical lidocaine for pediatric patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicity--seizures in an infant caused by (or related to) oral viscous lidocaine use. Smith, M., Wolfram, W., Rose, R.[2019]

A study analyzing data from 1995 to 2007 found that articaine 4 percent was significantly associated with neurosensory disturbances (NSDs), especially during mandibular block procedures, indicating a potential safety concern with this anesthetic.

The research suggests that neurotoxicity from the anesthetic itself, rather than the technique of needle penetration, is the primary cause of NSDs, leading to a recommendation for clinicians to consider lower concentration alternatives when performing block anesthesia in the trigeminal area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trigeminal nerve injury associated with injection of local anesthetics: needle lesion or neurotoxicity? Hillerup, S., Jensen, RH., Ersbøll, BK.[2019]

Topical administration of lidocaine can lead to serious toxicity, as demonstrated in a case where a patient experienced neurological issues (convulsions) and cardiological problems (ventricular fibrillation) during a thyroplasty procedure.

Despite the severe reactions, the patient's condition improved satisfactorily, highlighting the importance of monitoring for potential side effects even with local anesthetics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Toxicity of topical administration of lidocaine]. Gómez Martín-Zarco, JM., Lumbreras Fernández de Córdoba, J., Ortiz García, P.[2019]

In a study using Sprague Dawley rats, high doses of lidocaine given during specific periods of pregnancy did not show any toxicological or teratogenic effects on the fetuses.

Histological and physical examinations of the fetuses revealed normal development, indicating that lidocaine administration during pregnancy is unlikely to harm fetal health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicological assessment of lidocaine in the pregnant rat. Ramazzotto, LJ., Curro, FA., Paterson, JA., et al.[2017]

Lidocaine has demonstrated protective effects against brain damage in both animal models of ischemia and in vitro studies of low oxygen conditions, suggesting its potential as a neuroprotective agent.

Clinical investigations are exploring lidocaine's ability to prevent postoperative cognitive dysfunction, indicating its possible application in enhancing recovery after surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuroprotective effect of lidocaine: is there clinical potential? Leng, T., Gao, X., Dilger, JP., et al.[2020]

Chronic stress leads to learning and memory dysfunction and damage to pyramidal cells in the CA3 region of the hippocampus, as shown in a study with 32 mice over 21 days.

Lidocaine treatment significantly improved learning and memory performance in stressed mice, reducing the time taken to find a platform in a water maze and increasing the number of healthy pyramidal cells compared to the chronic stress group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effects of lidocaine on learning and memory dysfunction as well neuropathologic change induced by chronic stress: experiment with mice]. Hu, XY., Wang, DX.[2013]

Lidocaine effectively blocks motor axon conduction at the wrist, with complete recovery of muscle force and nerve conduction within 3 hours after administration, indicating its rapid anesthetic action.

However, even after conduction returns to normal, lidocaine causes prolonged impairment in motor axon excitability, suggesting that its effects may involve reversible structural changes to the nerve membrane, not just the blocking of voltage-gated sodium channels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transient impairment of the axolemma following regional anaesthesia by lidocaine in humans. Moldovan, M., Lange, KH., Aachmann-Andersen, NJ., et al.[2021]

Lidocaine, when used for spinal anesthesia, has been associated with a higher risk of neurotoxicity compared to other local anesthetics like bupivacaine and tetracaine, with a risk of persistent lumbosacral neuropathy occurring in about 1 in 1300 procedures for single injections and up to 1 in 200 for continuous spinal anesthesia.

Lidocaine is also linked to transient neurologic symptoms, which can cause significant pain in the buttocks or legs after anesthesia, affecting up to one third of patients, although this pain usually resolves within a week.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential neurotoxicity of spinal anesthesia with lidocaine. Johnson, ME.[2022]

N-ethyl lidocaine (QX-314) demonstrated neuroprotective effects in the striatum during ischemic conditions, showing partial recovery of brain function after oxygen and glucose deprivation in laboratory tests.

Unlike lidocaine, which significantly depressed neuronal activity, QX-314 preserved excitatory field potentials and neuronal firing, suggesting it may be a safer option for protecting brain cells during ischemic events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

N-ethyl lidocaine (QX-314) protects striatal neurons against ischemia: an in vitro electrophysiological study. Armogida, M., Giustizieri, M., Zona, C., et al.[2014]

References

1. United States pubmed.ncbi.nlm.nih.gov

Lidocaine overdose: another preventable case? [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Toxicity--seizures in an infant caused by (or related to) oral viscous lidocaine use. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Trigeminal nerve injury associated with injection of local anesthetics: needle lesion or neurotoxicity? [2019]

4. Spain pubmed.ncbi.nlm.nih.gov

[Toxicity of topical administration of lidocaine]. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Toxicological assessment of lidocaine in the pregnant rat. [2017]

6. United States pubmed.ncbi.nlm.nih.gov

Neuroprotective effect of lidocaine: is there clinical potential? [2020]

7. China pubmed.ncbi.nlm.nih.gov

[Effects of lidocaine on learning and memory dysfunction as well neuropathologic change induced by chronic stress: experiment with mice]. [2013]

8. England pubmed.ncbi.nlm.nih.gov

Transient impairment of the axolemma following regional anaesthesia by lidocaine in humans. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Potential neurotoxicity of spinal anesthesia with lidocaine. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

N-ethyl lidocaine (QX-314) protects striatal neurons against ischemia: an in vitro electrophysiological study. [2014]