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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Trigeminal Neuralgia

Intervention / Treatment
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* Drug: Lidocaine
* Drug: Guanfacine


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lidocaine then Lidocaine + Guanfacine<br>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<br>* 6 mL of 1% lidocaine<br>* Other names: Xylocaine;Drug: Guanfacine<br>* 250 mcg<br>|
| Experimental: Lidocaine + Guanfacine then Lidocaine<br>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<br>* 6 mL of 1% lidocaine<br>* Other names: Xylocaine;Drug: Guanfacine<br>* 250 mcg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to return to baseline pain after injection. | Time in (hours or days) until pain returns to baseline number. Pain will be measured on a visual analog scale 0-10 (0 = no pain, 10 = worst pain) | up to 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain intensity after treatment to be measured throughout follow-up | Pain will be measured on a visual analog scale 0-10 (0 = no pain, 10 = worst pain) | up to 2 weeks | 
| Quality of life after treatment | Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health version 1.2 [health-related quality of life] includes 10 questions and measures assess an individual's physical, mental, and social health. The adult PROMIS Global Health measure produces two scores: Physical Health and Mental Health. All items, except for the rating of pain, use a 1-5 rating, with higher ratings corresponding with better outcomes. The pain item will be recoded from a 1-10 scale to convert to a 1-5 scale, with higher ratings corresponding to better outcomes. The remaining two items (general health and social roles) are not used to calculate summary scores; these two questions use a 1-5 rating, with higher ratings corresponding with better outcomes. The raw scores for Physical Health and Mental Health will comprise a sum of the numerical responses for the four questions in each group. T scores will be calculated, with higher T scores corresponding with better outcomes. | up to 2 weeks | 
| Frequency of acute trigeminal nerve pain attacks during follow-up | Frequency of pain attacks | up to 2 weeks | 
| Time to first rescue medication during follow-up | Rescue medication (including opioid and non-opioid analgesics) use will be monitored once daily. | up to 2 weeks | 
| Total amount of rescue medications during follow-up | Rescue medication (including opioid and non-opioid analgesics) use will be monitored once daily. | up to 2 weeks |