Lidocaine + Clonidine for Intraoral Anesthesia in Patients With Diabetes Mellitus Type 2

Study Overview
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Brief Summary
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The purpose of this study is to determine whether 2% lidocaine (L) + clonidine (C) (15 mcg/ml) as a vasoconstrictor achieves efficient (equal or better parameters of intraoral local anesthesia in comparison to 2% lidocaine + epinephrine (E) (1:80 000)) and safe (stable cardiovascular parameters - systolic, diastolic, mean blood pressure and heart rate) intraoral local anesthesia in patients with Diabetes mellitus type 2.

Detailed Description
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Patients with diabetes mellitus type 2, represent a risk for performing regional anesthesia techniques due to microvascular (microangiopathy, neuropathy) and macrovascular (hypertension, coronary heart disease) complications. There is evidence that local anesthetic toxicity may be increased in diabetic setting due to underlying neuropathy; while interaction of diabetic blood vessels with vasoconstrictors may be of importance because of microangiopathic changes. Lately, regional anesthesia protocol in general surgery for patients with diabetes mellitus was released, proposing reduction of local anesthetic concentration and avoiding epinephrine as vasoconstrictor. Oral cavity tissues in diabetes mellitus also suffer from neuropathy (burning, paresthesia, teeth loss, temporomandibular dysfunction, xerostomia) and microangiopathy (periodontal disease, salivary gland dysfunction). Most widely used vasoconstrictor for intraoral local anesthesia, epinephrine, is an alpha- and beta- adrenergic agonist. Because of its beta-adrenergic effects, epinephrine could adversely affect cardiovascular function, especially in risk patients. There are data suggesting that intraoral local anesthesia obtained with 2% lidocaine with clonidine, selective alpha 2-adrenoceptor agonist as a vasoconstrictor, is characterized with significantly more stable cardiovascular parameters and similar parameters of local anesthesia with respect to lidocaine with epinephrine in healthy and hypertensive patients. With regard to aforementioned, the aim of this randomized double-blind controlled clinical trial is to evaluate and compare efficacy and safety of intraoral local anesthesia obtained with 2% lidocaine (L) + clonidine (15 mcg/ml) (C) or 2% L + epinephrine (1:80 000) (E), comparing healthy and diabetes mellitus type 2 patients. Prior to tooth extraction, random allocation to one of four groups (L+C maxillary infiltration, L+C mandibular block, L+E maxillary infiltration and L+E mandibular block) is performed for diabetic (30 per group) and healthy (30 per group) patients. Parameters of local anesthesia (onset, duration, intensity, width of anesthetic field for maxillary infiltration), cardiovascular parameters (systolic, diastolic, mean arterial pressure; heart rate and electrocardiographic changes), quality of postoperative analgesia (assessed by Visual Analogue Scale, Numerical Rating Scale and number of consumed analgesics) and postoperative complications (infection, bleeding, paresthesia, delayed wound healing) are evaluated and compared.

Official Title
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Efficacy and Safety of Intraoral Local Anesthesia by Lidocaine + Clonidine in Patients With Diabetes Mellitus Type 2

Conditions
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Diabetes Mellitus, Local Anesthesia

Intervention / Treatment
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* Drug: L+C maxillary anesthesia
* Drug: L+C mandibular anesthesia
* Drug: L+E maxillary anesthesia
* Drug: L+E mandibular anesthesia


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy participants: ASA I Diabetic type 2 participants: ASA III (HbA1c level < 9%) Required a single-root teeth indicated for non-complicated extraction Dental diagnosis of periodontal disease, tooth fracture, chronic periapical lesion and root infection Subjects give informed written consent Exclusion Criteria: Pregnancy and lactation Allergy to used drugs and food Hepatic and/or renal failure ASA IV patients Tobacco smokers History of alcoholism and/or drug abuse and addiction

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Diabetics: L+C maxillary anesthesia<br>Single dose intraoral local anesthesia with 2ml lidocaine (2%) + clonidine (15 mcg/ml) for maxillary infiltration anesthesia | Drug: L+C maxillary anesthesia<br>* Maxillary anesthesia obtained by 2% lidocaine + clonidine (15 mcg/ml)<br>|
| Experimental: Diabetics: L+C mandibular anesthesia<br>Single dose intraoral local anesthesia with 2ml lidocaine (2%) + clonidine (15 mcg/ml) for mandibular block anesthesia | Drug: L+C mandibular anesthesia<br>* Mandibular anesthesia obtained by 2% lidocaine + clonidine (15 mcg/ml)<br>|
| Active Comparator: Diabetics: L+E maxillary anesthesia<br>Single dose intraoral local anesthesia with 2ml lidocaine (2%)+ epinephrine (1:80.000) for maxillary infiltration anesthesia | Drug: L+E maxillary anesthesia<br>* Maxillary anesthesia obtained by 2% lidocaine + epinephrine (1:80 000)<br>|
| Active Comparator: Diabetics: L+E mandibular anesthesia<br>Single dose intraoral local anesthesia with 2ml lidocaine (2%) + epinephrine (1:80.000) for mandibular block anesthesia | Drug: L+E mandibular anesthesia<br>* Mandibular anesthesia obtained by 2% lidocaine + epinephrine (1:80 000)<br>|
| Experimental: Healthy: L+C maxillary anesthesia<br>Single dose intraoral local anesthesia with 2ml lidocaine (2%) + clonidine (15 mcg/ml) for maxillary infiltration anesthesia | Drug: L+C maxillary anesthesia<br>* Maxillary anesthesia obtained by 2% lidocaine + clonidine (15 mcg/ml)<br>|
| Experimental: Healthy: L+C mandibular anesthesia<br>Single dose intraoral local anesthesia with 2ml lidocaine (2%) + clonidine (15 mcg/ml) for mandibular block anesthesia | Drug: L+C mandibular anesthesia<br>* Mandibular anesthesia obtained by 2% lidocaine + clonidine (15 mcg/ml)<br>|
| Active Comparator: Healthy: L+E maxillary anesthesia<br>Single dose intraoral local anesthesia with 2ml lidocaine (2%)+ epinephrine (1:80.000) for maxillary infiltration anesthesia | Drug: L+E maxillary anesthesia<br>* Maxillary anesthesia obtained by 2% lidocaine + epinephrine (1:80 000)<br>|
| Active Comparator: Healthy: L+E mandibular anesthesia<br>Single dose intraoral local anesthesia with 2ml lidocaine (2%) + epinephrine (1:80.000) for mandibular block anesthesia | Drug: L+E mandibular anesthesia<br>* Mandibular anesthesia obtained by 2% lidocaine + epinephrine (1:80 000)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Intraoral Local Anesthesia | Time until cessation in soft tissue numbness | Up to 6 hours after local anesthesia injection | 
| Intensity of Intraoral Local Anesthesia | Number of participants who reported values > 0 after pin-prick testing, using Visual Analogue Scale (VAS) and Numerical Rating Scale (NRS). VAS is represented by line 100 mm long, with one end marked with 0 and words no pain , while the other end is marked with 100 and words the worst pain imanginable. VRS scale is represented by line 100 mm long, marked with numbers from 0 to 10, where 0 corresponds to no pain, and 10 corresponds to the worst pain imaginable. For both scales, higher scores represent worse outcomes. | Up to 10 minutes after local anesthesia injection | 
| Baseline Systolic Blood Pressure |  | Baseline, 0 minutes | 
| Systolic Blood Pressure at 10 Minutes | Systolic blood pressure values 5 minutes after local anesthesia injection | 10th minute | 
| Systolic Blood Pressure at 15 Minutes | Systolic blood pressure values 10 minutes after local anesthesia injection | 15th minute | 
| Systolic Blood Pressure at 20 Minutes | Systolic blood pressure values 15 minutes after local anesthesia injection | 20th minute | 
| Systolic Blood Pressure at 35 Minutes | Systolic blood pressure values 30 minutes after local anesthesia injection | 35th minute | 
| Baseline Diastolic Blood Pressure |  | baseline, 0 minutes | 
| Diastolic Blood Pressure at 10 Minutes | Diastolic blood pressure values 5 minutes after local anesthesia injection | 10th minute | 
| Diastolic Blood Pressure at 15 Minutes | Diastolic blood pressure values 10 minutes after local anesthesia injection | 15th minute | 
| Diastolic Blood Pressure at 20 Minutes | Diastolic blood pressure values 15 minutes after local anesthesia injection | 20th minute | 
| Diastolic Blood Pressure at 35 Minutes | Diastolic blood pressure values 30 minutes after local anesthesia injection | 35th minute | 
| Baseline Values of Heart Rate |  | baseline, 0 minutes | 
| Heart Rate at 10 Minutes | Heart rate 5 minutes after local anesthesia injection, 10 minutes after baseline measurement | 10th minute | 
| Heart Rate at 15 Minutes | Heart rate 10 minutes after local anesthesia injection, 15 minutes after baseline measurement | 15th minute | 
| Heart Rate at 20 Minutes | Heart rate 15 minutes after local anesthesia injection, 20 minutes after baseline measurement | 20th minute | 
| Ceart Rate at 35 Minutes | Heart rate 30 minutes after local anesthesia injection, 35 minutes after baseline measurement | 35th minute | 
| Baseline Electrocardiogram |  | baseline, 0 minutes | 
| Electrocardiogram at 10 Minutes | ECG 5 minutes after local anesthesia injection, 10 minutes after baseline measurement | 10th minute | 
| Electrocardiogram at 15 Minutes | ECG 10 minutes after local anesthesia injection, 15 minutes after baseline measurement | 15th minute | 
| Electrocardiogram at 20 Minutes | ECG 15 minutes after local anesthesia injection, 20 minutes after baseline measurement | 20th minute | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Onset of Intraoral Local Anesthesia | Evaluated by pin-prick after subjective feeling of soft tissue numbness appeared after local anesthesia injection | Up to 10 minutes, until subjective feeling of soft tissue numbnes | 
| Width of Anesthetic Field After Maxillary Infiltration Anesthesia | Soft tissue numbness area determined by pin-prick test after maxillary infiltration anesthesia. Not tested for mandibular ablock anesthesia. | Up to 10 minutes after injection of local anesthesia | 
| Postoperative Analgesia | Number of participants who experienced postoperative pain, VAS, NRS | up to 24 hours after tooth extraction | 
| Local Postoperative Complications | Postoperative paresthesia by clinical examination | 24 hours, 7 days |