Efficacy of Guanfacine and Lidocaine Combination in Trigeminal Nerve Block for Pain Management in Trigeminal Neuropathy

A Randomized, Double-Blind, 2-Way Crossover Trial to Assess the Efficacy of Guanfacine and Lidocaine Combination Versus Lidocaine Alone in Trigeminal Nerve Block for Pain Management in Painful Trigeminal Neuropathy Patients

A phenome-wide association study (PheWAS) identified an association between a loss of function variant in the human alpha 2B adrenergic receptor gene and trigeminal nerve disorders. Guanfacine is the oldest alpha-2 adrenergic agonist in clinical use and is approved for hypertension and attention deficit hyperactivity disorder. We hypothesize that guanfacine will be an effective adjunct to lidocaine for the treatment of neuropathic pain by enhancing and prolonging pain relief due to its activation of alpha-2 adrenergic receptors. The objectives of the study will be to evaluate the efficacy and safety of guanfacine in combination with lidocaine for trigeminal nerve block procedures for pain management in trigeminal neuralgia patients. This study will evaluate the efficacy of guanfacine in reducing acute pain and extending duration of pain relief when delivered in combination with lidocaine as a trigeminal nerve block, measured by Visual Analog Scale (VAS) data collected at specific time points after each injection.

Study Overview

• Status: Completed
• Conditions: Trigeminal Neuralgia
• Intervention / Treatment: Drug: Lidocaine; Drug: Guanfacine

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Vanderbilt University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Ability to understand and read English
• History of painful trigeminal neuropathy with persistent background facial pain severity > 5/10 on VAS
• Experience pain with a score of greater than 5 on a 0-10 scale (VAS) in the previous 24 hours before procedural treatment and at the time of procedural treatment.
• Eligible for trigeminal nerve block procedure and have not had a trigeminal nerve block procedure for pain management prior to the enrollment in the current study.
• Able to provide informed consent.

Exclusion Criteria:

• Presence of a significant structural lesion (e.g., tumor) as the cause of pain as shown in at least one neuroimaging study.
• Current diagnosis of fibromyalgia, temporomandibular disorders (TMD), odontogenic pain or other orofacial pain deemed unrelated to the trigeminal nerve as the origin.
• Allergy or any other hypersensitivity reactions to guanfacine or lidocaine or local anesthetic of the amide type, or to both iodinated contrast and gadolinium contrast.
• Females who are pregnant or breastfeeding and/or plan to become pregnant or to breastfeed during study participation.
• Participation in another investigational drug study within 30 days before randomization.
• Inability to understand the requirements of the study, inability to abide by the study restrictions, inability to fill out the questionnaires, or inability to return for the required treatments.
• Any clinically significant medical or surgical condition that in the investigator's opinion could interfere with the administration of study drug, interpretation of study results, or compromise the safety or well-being of the subject (i.e. infection, unable to stop anticoagulants).
• No reliable access to telephone service to allow for contact with study personnel.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lidocaine then Lidocaine + Guanfacine; Trigeminal nerve block will be performed with injection of 6 mL of 1% lidocaine (Day 1). Patient will return between Day 15-28 and trigeminal nerve block will be performed with injection of 6 mL of 1% lidocaine + 250 mcg guanfacine.	Drug: Lidocaine; 6 mL of 1% lidocaine; Other Names: Xylocaine; Drug: Guanfacine; 250 mcg
Experimental: Lidocaine + Guanfacine then Lidocaine; Trigeminal nerve block will be performed with injection of 6 mL of 1% lidocaine + 250 mcg guanfacine (Day 1). Patient will return between Day 15-28 and trigeminal nerve block will be performed with injection of 6 mL of 1% lidocaine.	Drug: Lidocaine; 6 mL of 1% lidocaine; Other Names: Xylocaine; Drug: Guanfacine; 250 mcg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Return to Baseline Pain After Injection.	Time (hours) until pain returns to baseline number.	up to 2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain Intensity in Follow-Up	Pain Intensity after treatment measured throughout the 8-hour follow-up period on a visual analog scale (VAS) from 0 to 10, where 0 is the least pain and 10 is the most pain.	8 hours
Quality of Life, Physical Health	Participant Quality of Life as measured by the PROMIS Global Health -10 SF during the 14-day follow-up. The scores reported are T-scores. The T-score rescales the raw sum score into a standardized score with a mean of 50 and a standard deviation (SD) of 10. Therefore a person with a T-score of 40 is one SD below the mean and a person with a T-score of 60 is one SD above the mean. For the Physical Health subscale, raw scores are converted into t-scores ranging from 16.2 to 67.7 and higher t-scores are indicative of better overall physical health.	14 days
Quality of Life, Mental Health	Participant Quality of Life as measured by the PROMIS Global Health -10 SF during the 14-day follow-up. The scores reported are T-scores. The T-score rescales the raw sum score into a standardized score with a mean of 50 and a standard deviation (SD) of 10. Therefore a person with a T-score of 40 is one SD below the mean and a person with a T-score of 60 is one SD above the mean. In this Mental Health subscale, raw scores are converted into t-scores ranging from 21.2 to 67.6, where higher t-scores are indicative of better overall physical health.	14 days
Frequency of Nerve Pain Attacks	Frequency of nerve pain attacks during the 14-day follow-up period. Pain frequency was recorded numerically as 0 - None (no pain), 1 - Weekly, 2 - Daily, 3 - Hourly, and 4 - Constant pain. Data was not collected at baseline, only at Day 7 and Day 14.	14 days
Rescue Medication Use	Number of participants using rescue medication during the 8-hour follow-up period	8 hours
Time to First Rescue Medication	Time, in hours, to use of first rescue medication in the follow-up period following the injection.	14 days

Collaborators and Investigators

• Sponsor: Vanderbilt University Medical Center
• Investigators: Principal Investigator: Tigran Kesayan, MD, Vanderbilt University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): November 4, 2019
• Primary Completion (Actual): October 4, 2023
• Study Completion (Actual): January 31, 2024

Study Registration Dates

• First Submitted: March 1, 2019
• First Submitted That Met QC Criteria: March 5, 2019
• First Posted (Actual): March 7, 2019

Study Record Updates

• Last Update Posted (Actual): March 30, 2025
• Last Update Submitted That Met QC Criteria: March 28, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Mouth Diseases; Stomatognathic Diseases; Nervous System Diseases; Neuromuscular Diseases; Peripheral Nervous System Diseases; Cranial Nerve Diseases; Facial Neuralgia; Facial Nerve Diseases; Neuralgia; Trigeminal Neuralgia; Trigeminal Nerve Diseases; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Anesthetics, Local; Anesthetics; Central Nervous System Depressants; Sensory System Agents; Neurotransmitter Agents; Anti-Arrhythmia Agents; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Membrane Transport Modulators; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Adrenergic Agents; Antihypertensive Agents; Lidocaine; Guanfacine
• Other Study ID Numbers: TN

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No