Clinical Trial Comparing Effectiveness of Buffered Versus Unbuffered Local Anesthetic in Children Ages 10-12 Years

Study Overview
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Brief Summary
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Local anesthesia is an integral part of clinical pediatric dental practice, but it has challenges. It can be uncomfortable for children, and the risk of adverse events limits how much is used. Some evidence suggests benefits of buffering local anesthetics including equal effect with less pain on injection. These findings have not been replicated and validated among pediatric populations, creating a gap in the knowledge base. To address this knowledge gap and contribute to the evidence base on safety and efficacy of local anesthesia in pediatric dentistry, this investigation proposes to compare the anesthetic effects of buffered 1% lidocaine with those of unbuffered 2%, among children. The specific aims of this investigation are to determine differences between buffered 1% and unbuffered 2% lidocaine (both with 1:100,000 epinephrine) used for inferior alveolar nerve block (IAN) anesthesia, in the following domains: Pain experience on injection, time to onset following the administration, and time to recovery [subjective] Blood lidocaine levels 15 minutes following the administration and duration of pulpal anesthesia [objective] Null Hypotheses: No difference exists in anesthetic effectiveness for pulpal anesthesia after intraoral IAN block between buffered 1% Lidocaine with 1:100,000 epinephrine as compared to unbuffered 2% Lidocaine with 1:100,000 epinephrine. No differences exist in peak blood lidocaine levels, pain on injection, time to lip numbness, and duration of anesthesia between the two drug formulations. Randomized subjects will be injected orally for bottom jaw anesthesia, with 3cc of buffered 1% lidocaine (30mg) 1:100,000 epinephrine or 3cc unbuffered of 2% lidocaine (60mg) 1:100,000 epinephrine. The injectable volume of the buffered formulation will include 0.3cc of 8.4% sodium bicarbonate. One faculty member in the Department of Pediatric Dentistry at the University of North Carolina (UNC) School of Dentistry will administer the drugs in the Pediatric Dentistry clinic. The same clinician will administer injection to the same subjects at both visits. Clinicians and subjects will not know which drug formulation is given at which appointment. A clinician will measure the level of discomfort on injection, how long it takes for the lip to be numb, how long it takes for the first molar tooth in that area to be numb, how long it takes the local anesthetic to wear off, and how much of the anesthetic is in the blood.

Official Title
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Pilot Study: Comparison of Buffered 1% vs. Unbuffered 2% Lidocaine in Pediatric Subjects; Clinical Outcomes

Conditions
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Anesthesia, Local, Pain

Intervention / Treatment
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* Drug: 1% Buffered Lidocaine 1:100,000 Epinephrine
* Drug: 2% Unbuffered Lidocaine 1:100,000 Epinephrine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 10-12 years American Society of Anesthesiologists (ASA) Class I (Healthy) Body Weight: the Interquartile Range (IQR) 33-60Kg for subject ages Have ability to speak and read English Willingness to participate in two sessions No history of adverse reaction to dental anesthetic Have bilateral, disease/symptom-free mandibular first molars present Exclusion Criteria: Allergy to lidocaine class of anesthetic drugs Local anesthetic drug use in past week Current symptomatic teeth or oral mucosa ASA II or above (including asthma)

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 12 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: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Study subjects will serve as their own controls in this crossover AB/BA study design which is uniform within sequences (groups, i.e. AB/BA, of order of drug formulation administration), uniform within periods (equal time between administration of alternating drug formulations), and balanced (equal number of subjects within each study arm). The randomization will be performed to the type of drug given first, using a balanced randomization (half subjects buffered, half unbuffered) implemented with SAS software routines. During the first session, each subject will receive an IAN block with the first randomly assigned anesthetic formulation using the Halstead technique. At least a week later, substantially longer than the elimination half-life of the drug lidocaine (1.5-2hr), local anesthetic injections will be done using the alternate local anesthetic formulation.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Buffered Anesthetic, then Unbuffered Anesthetic<br>Subjects randomized to Buffered Anesthetic, then Unbuffered Anesthetic will first receive an injection with 1% Buffered Lidocaine 1:100,000 Epinephrine. After one week minimum washout period, subjects will then receive an injection with 2% Unbuffered Lidocaine 1:100,000 Epinephrine. | Drug: 1% Buffered Lidocaine 1:100,000 Epinephrine<br>* A single IAN block with 3cc 1% Buffered Lidocaine (30mg) 1:100,000 Epinephrine using the Halstead technique.<br>* Other names: Xylocaine;Drug: 2% Unbuffered Lidocaine 1:100,000 Epinephrine<br>* A single IAN block with 3cc 2% Unbuffered Lidocaine (60mg) 1:100,000 Epinephrine using the Halstead technique.<br>* Other names: Xylocaine;|
| Experimental: Unbuffered Anesthetic, then Buffered Anesthetic<br>Subjects randomized to Unbuffered Anesthetic, then Buffered Anesthetic will first receive an injection with 2% Unbuffered Lidocaine 1:100,000 Epinephrine. After one week minimum washout period, subjects will then receive an injection with 1% Buffered Lidocaine 1:100,000 Epinephrine. | Drug: 1% Buffered Lidocaine 1:100,000 Epinephrine<br>* A single IAN block with 3cc 1% Buffered Lidocaine (30mg) 1:100,000 Epinephrine using the Halstead technique.<br>* Other names: Xylocaine;Drug: 2% Unbuffered Lidocaine 1:100,000 Epinephrine<br>* A single IAN block with 3cc 2% Unbuffered Lidocaine (60mg) 1:100,000 Epinephrine using the Halstead technique.<br>* Other names: Xylocaine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Pain Scores Following Injection | Perceived pain on injection, self-reported verbally using a Likert scale from 1-10, with lower numbers corresponding to less pain (1 = no pain, 10 = worst pain imaginable). Lower scores reflect a lesser degree of pain. | Within 10 minutes of injection | 
| Mean Time to Lower Lip Numbness Following Injection | Time in minutes beginning immediately following injection to patient-reported lip numbness | Up to 30 minutes following injection | 
| Average Serum Lidocaine Concentration at 15 Minutes Post Injection | Blood Lidocaine Level (mcg/mL) as measured in 10cc venous blood, taken 15 minutes following injection. Blood assayed for serum lidocaine levels with a Sciex TripleTOF liquid chromatography- mass spectrometry (LC-MS) equipped with a C18 Hypersil (10mm x 2.1mm, 3.0μm). | One blood draw taken 15 minutes following injection | 
| Mean Time to Baseline Lip Sensation | Response in minutes from injection to when lip is no longer numb, as self reported by patient. | Within 24 hours following injection | 
| Number of Participants Who Respond to Cold Stimulus (Positive/Negative) Prior to Injection | Response to experiencing sensation to cold stimulus on permanent molar tooth prior to injection | 5 minutes prior to injection | 
| Number of Participants Who Respond to Cold Stimulus (Positive/Negative) 30 Minutes Following Injection | Response to experiencing sensation to cold stimulus on permanent molar tooth 30 minutes following injection | 30 minutes following injection | 
| Number of Participants Who Respond to Cold Stimulus (Positive/Negative) 60 Minutes Following Injection | Response to experiencing sensation to cold stimulus on permanent molar tooth 60 minutes following injection | 60 minutes following injection | 
| Number of Participants Who Respond to Cold Stimulus (Positive/Negative) 90 Minutes Following Injection | Response to experiencing sensation to cold stimulus on permanent molar tooth 90 minutes following injection | 90 minutes following injection | 
| Number of Participants Who Respond to Cold Stimulus (Positive/Negative) 120 Minutes Following Injection | Response to experiencing sensation to cold stimulus on permanent molar tooth 120 minutes following injection | 120 minutes following injection | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Healthy pediatric volunteers