Lidocaine + Clonidine for Intraoral Anesthesia in Patients With Diabetes Mellitus Type 2 (LCIOADMT2)

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

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.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus; Local Anesthesia
• Intervention / Treatment: Drug: L+C maxillary anesthesia; Drug: L+C mandibular anesthesia; Drug: L+E maxillary anesthesia; Drug: L+E mandibular anesthesia

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 256
• Phase: Phase 3

Contacts and Locations

Study Locations

• Serbia
  • Belgrade, Serbia, 11000
    • School of dental medicine, University of Belgrade

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

8

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Belgrade
• Investigators: Principal Investigator: Dragica DM Stojic, DDS, PhD, School of dental medicine, University of Belgrade; Principal Investigator: Bozidar M Brkovic, DDS, PhD, School of dental medicine, University of Belgrade; Principal Investigator: Marija S Milic, DDS, School of dental medicine, University of Belgrade

Study record dates

Study Major Dates

• Study Start: June 1, 2013
• Primary Completion (Actual): January 1, 2016
• Study Completion (Actual): January 1, 2016

Study Registration Dates

• First Submitted: February 4, 2015
• First Submitted That Met QC Criteria: February 19, 2015
• First Posted (Estimate): February 26, 2015

Study Record Updates

• Last Update Posted (Actual): May 3, 2017
• Last Update Submitted That Met QC Criteria: March 22, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics
• Other Study ID Numbers: UBelgrade 534/2; 175021 (Other Grant/Funding Number: Ministry of Education, Science and Technological Development)