Trigeminal Neuralgia
Conditions
Brief summary
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.
Interventions
DRUGLidocaine
6 mL of 1% lidocaine
DRUGGuanfacine
250 mcg
Sponsors
Vanderbilt University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Return to Baseline Pain After Injection. | up to 2 weeks | Time (hours) until pain returns to baseline number. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Quality of Life, Physical Health | 14 days | 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. |
| Quality of Life, Mental Health | 14 days | 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. |
| Pain Intensity in Follow-Up | 8 hours | 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. |
| Rescue Medication Use | 8 hours | Number of participants using rescue medication during the 8-hour follow-up period |
| Time to First Rescue Medication | 14 days | Time, in hours, to use of first rescue medication in the follow-up period following the injection. |
| Frequency of Nerve Pain Attacks | 14 days | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
Lidocaine: 6 mL of 1% lidocaine
Guanfacine: 250 mcg | 18 |
| 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.
Lidocaine: 6 mL of 1% lidocaine
Guanfacine: 250 mcg | 19 |
| Total | 37 |
Baseline characteristics
| Characteristic | Lidocaine Then Lidocaine + Guanfacine | Total | Lidocaine + Guanfacine Then Lidocaine |
|---|---|---|---|
| Age, Continuous | 51.5 years | 60.0 years | 60.1 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 16 Participants | 35 Participants | 19 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 17 Participants | 35 Participants | 18 Participants |
| Region of Enrollment United States | 18 participants | 37 participants | 19 participants |
| Sex: Female, Male Female | 16 Participants | 32 Participants | 16 Participants |
| Sex: Female, Male Male | 2 Participants | 5 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 36 | 0 / 28 |
| other Total, other adverse events | 2 / 36 | 1 / 28 |
| serious Total, serious adverse events | 0 / 36 | 0 / 28 |
Outcome results
Primary
Time to Return to Baseline Pain After Injection.
Time (hours) until pain returns to baseline number.
Time frame: up to 2 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lidocaine Alone | Time to Return to Baseline Pain After Injection. | 8 hours |
| Lidocaine + Guanfacine | Time to Return to Baseline Pain After Injection. | 5 hours |
p-value: 0.374Regression, Cox
Secondary
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.
Time frame: 14 days
Population: The overall number of participants analyzed corresponds with how many participants were injected; however, not every participant responded at every timepoint. Therefore, only recorded responses at each timeline were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lidocaine Alone | Frequency of Nerve Pain Attacks | Day 7 | 3.64 units on a scale | Standard Deviation 1.11 |
| Lidocaine Alone | Frequency of Nerve Pain Attacks | Day 14 | 3.61 units on a scale | Standard Deviation 1.15 |
| Lidocaine + Guanfacine | Frequency of Nerve Pain Attacks | Day 7 | 3.70 units on a scale | Standard Deviation 1.17 |
| Lidocaine + Guanfacine | Frequency of Nerve Pain Attacks | Day 14 | 3.81 units on a scale | Standard Deviation 0.83 |
p-value: 0.907Proportional Odds Regression
Secondary
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.
Time frame: 8 hours
Population: The overall number of participants analyzed corresponds with how many participants were injected; however, not every participant responded at every timepoint. Therefore, only recorded responses at each timeline were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lidocaine Alone | Pain Intensity in Follow-Up | 3 hours | 2.84 score on a scale | Standard Deviation 2.38 |
| Lidocaine Alone | Pain Intensity in Follow-Up | 1 hour | 2.24 score on a scale | Standard Deviation 2.2 |
| Lidocaine Alone | Pain Intensity in Follow-Up | 3.5 hours | 3.03 score on a scale | Standard Deviation 2.37 |
| Lidocaine Alone | Pain Intensity in Follow-Up | 5 hours | 3.65 score on a scale | Standard Deviation 2.12 |
| Lidocaine Alone | Pain Intensity in Follow-Up | 0 hours | 6.75 score on a scale | Standard Deviation 1.56 |
| Lidocaine Alone | Pain Intensity in Follow-Up | 5.5 hours | 3.69 score on a scale | Standard Deviation 2.14 |
| Lidocaine Alone | Pain Intensity in Follow-Up | 1.5 hours | 2.83 score on a scale | Standard Deviation 2.6 |
| Lidocaine Alone | Pain Intensity in Follow-Up | 6 hours | 3.31 score on a scale | Standard Deviation 2.24 |
| Lidocaine Alone | Pain Intensity in Follow-Up | 4.5 hours | 2.79 score on a scale | Standard Deviation 2.18 |
| Lidocaine Alone | Pain Intensity in Follow-Up | 6.5 hours | 3.42 score on a scale | Standard Deviation 2.17 |
| Lidocaine Alone | Pain Intensity in Follow-Up | 2 hours | 2.47 score on a scale | Standard Deviation 2.26 |
| Lidocaine Alone | Pain Intensity in Follow-Up | 7 hours | 3.76 score on a scale | Standard Deviation 2.4 |
| Lidocaine Alone | Pain Intensity in Follow-Up | 0.5 hours | 1.91 score on a scale | Standard Deviation 2.31 |
| Lidocaine Alone | Pain Intensity in Follow-Up | 7.5 hours | 3.52 score on a scale | Standard Deviation 2.65 |
| Lidocaine Alone | Pain Intensity in Follow-Up | 2.5 hours | 2.7 score on a scale | Standard Deviation 2.53 |
| Lidocaine Alone | Pain Intensity in Follow-Up | 8 hours | 3.56 score on a scale | Standard Deviation 2.53 |
| Lidocaine Alone | Pain Intensity in Follow-Up | 4 hours | 2.74 score on a scale | Standard Deviation 2.18 |
| Lidocaine + Guanfacine | Pain Intensity in Follow-Up | 8 hours | 2.68 score on a scale | Standard Deviation 2.25 |
| Lidocaine + Guanfacine | Pain Intensity in Follow-Up | 4 hours | 2.04 score on a scale | Standard Deviation 2.49 |
| Lidocaine + Guanfacine | Pain Intensity in Follow-Up | 4.5 hours | 2.29 score on a scale | Standard Deviation 2.41 |
| Lidocaine + Guanfacine | Pain Intensity in Follow-Up | 0 hours | 6.63 score on a scale | Standard Deviation 1.43 |
| Lidocaine + Guanfacine | Pain Intensity in Follow-Up | 0.5 hours | 1.88 score on a scale | Standard Deviation 2.72 |
| Lidocaine + Guanfacine | Pain Intensity in Follow-Up | 1 hour | 1.54 score on a scale | Standard Deviation 2.25 |
| Lidocaine + Guanfacine | Pain Intensity in Follow-Up | 1.5 hours | 1.42 score on a scale | Standard Deviation 1.98 |
| Lidocaine + Guanfacine | Pain Intensity in Follow-Up | 2 hours | 1.81 score on a scale | Standard Deviation 2.11 |
| Lidocaine + Guanfacine | Pain Intensity in Follow-Up | 2.5 hours | 2.21 score on a scale | Standard Deviation 2.45 |
| Lidocaine + Guanfacine | Pain Intensity in Follow-Up | 3 hours | 2.4 score on a scale | Standard Deviation 2.61 |
| Lidocaine + Guanfacine | Pain Intensity in Follow-Up | 5 hours | 2.58 score on a scale | Standard Deviation 2.44 |
| Lidocaine + Guanfacine | Pain Intensity in Follow-Up | 5.5 hours | 3.0 score on a scale | Standard Deviation 2.81 |
| Lidocaine + Guanfacine | Pain Intensity in Follow-Up | 6 hours | 2.67 score on a scale | Standard Deviation 2.45 |
| Lidocaine + Guanfacine | Pain Intensity in Follow-Up | 6.5 hours | 2.81 score on a scale | Standard Deviation 2.23 |
| Lidocaine + Guanfacine | Pain Intensity in Follow-Up | 7 hours | 2.79 score on a scale | Standard Deviation 2.17 |
| Lidocaine + Guanfacine | Pain Intensity in Follow-Up | 7.5 hours | 2.85 score on a scale | Standard Deviation 2.19 |
| Lidocaine + Guanfacine | Pain Intensity in Follow-Up | 3.5 hours | 2.38 score on a scale | Standard Deviation 2.45 |
p-value: <0.001Regression, Logistic
Secondary
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.
Time frame: 14 days
Population: The overall number of participants analyzed corresponds with how many participants were injected; however, not every participant responded at every timepoint. Therefore, only recorded responses at each timeline were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lidocaine Alone | Quality of Life, Mental Health | Day 0 | 44.98 T-score | Standard Deviation 10.47 |
| Lidocaine Alone | Quality of Life, Mental Health | Day 7 | 44.34 T-score | Standard Deviation 8.42 |
| Lidocaine Alone | Quality of Life, Mental Health | Day 14 | 43.78 T-score | Standard Deviation 7.91 |
| Lidocaine + Guanfacine | Quality of Life, Mental Health | Day 0 | 44.4 T-score | Standard Deviation 8.93 |
| Lidocaine + Guanfacine | Quality of Life, Mental Health | Day 7 | 46.07 T-score | Standard Deviation 8.42 |
| Lidocaine + Guanfacine | Quality of Life, Mental Health | Day 14 | 45.72 T-score | Standard Deviation 9.91 |
p-value: 0.099Regression, Linear
Secondary
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.
Time frame: 14 days
Population: The overall number of participants analyzed corresponds with how many participants were injected; however, not every participant responded at every timepoint. Therefore, only recorded responses at each timeline were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lidocaine Alone | Quality of Life, Physical Health | Day 0 | 40.35 T-score | Standard Deviation 6.66 |
| Lidocaine Alone | Quality of Life, Physical Health | Day 7 | 42.88 T-score | Standard Deviation 6.47 |
| Lidocaine Alone | Quality of Life, Physical Health | Day 14 | 42.83 T-score | Standard Deviation 7.89 |
| Lidocaine + Guanfacine | Quality of Life, Physical Health | Day 0 | 39.86 T-score | Standard Deviation 6.07 |
| Lidocaine + Guanfacine | Quality of Life, Physical Health | Day 7 | 43.2 T-score | Standard Deviation 6.3 |
| Lidocaine + Guanfacine | Quality of Life, Physical Health | Day 14 | 41.67 T-score | Standard Deviation 7.16 |
p-value: 0.775Regression, Linear
Secondary
Rescue Medication Use
Number of participants using rescue medication during the 8-hour follow-up period
Time frame: 8 hours
Population: The overall number of participants analyzed corresponds with how many participants were injected; however, not every participant responded at every timepoint. Therefore, only recorded responses at each timeline were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Lidocaine Alone | Rescue Medication Use | 4 hours | 1 Participants |
| Lidocaine Alone | Rescue Medication Use | 0.5 hours | 2 Participants |
| Lidocaine Alone | Rescue Medication Use | 5.5 hours | 2 Participants |
| Lidocaine Alone | Rescue Medication Use | 1 hour | 0 Participants |
| Lidocaine Alone | Rescue Medication Use | 7 hours | 3 Participants |
| Lidocaine Alone | Rescue Medication Use | 1.5 hours | 3 Participants |
| Lidocaine Alone | Rescue Medication Use | 4.5 hours | 3 Participants |
| Lidocaine Alone | Rescue Medication Use | 2 hours | 3 Participants |
| Lidocaine Alone | Rescue Medication Use | 7.5 hours | 5 Participants |
| Lidocaine Alone | Rescue Medication Use | 2.5 hours | 1 Participants |
| Lidocaine Alone | Rescue Medication Use | 6 hours | 2 Participants |
| Lidocaine Alone | Rescue Medication Use | 3 hours | 4 Participants |
| Lidocaine Alone | Rescue Medication Use | 8 hours | 7 Participants |
| Lidocaine Alone | Rescue Medication Use | 3.5 hours | 1 Participants |
| Lidocaine Alone | Rescue Medication Use | 0 hours | 16 Participants |
| Lidocaine Alone | Rescue Medication Use | 6.5 hours | 1 Participants |
| Lidocaine Alone | Rescue Medication Use | 5 hours | 3 Participants |
| Lidocaine + Guanfacine | Rescue Medication Use | 8 hours | 1 Participants |
| Lidocaine + Guanfacine | Rescue Medication Use | 4.5 hours | 2 Participants |
| Lidocaine + Guanfacine | Rescue Medication Use | 4 hours | 1 Participants |
| Lidocaine + Guanfacine | Rescue Medication Use | 5 hours | 2 Participants |
| Lidocaine + Guanfacine | Rescue Medication Use | 5.5 hours | 1 Participants |
| Lidocaine + Guanfacine | Rescue Medication Use | 6 hours | 1 Participants |
| Lidocaine + Guanfacine | Rescue Medication Use | 6.5 hours | 3 Participants |
| Lidocaine + Guanfacine | Rescue Medication Use | 7 hours | 2 Participants |
| Lidocaine + Guanfacine | Rescue Medication Use | 7.5 hours | 2 Participants |
| Lidocaine + Guanfacine | Rescue Medication Use | 0 hours | 12 Participants |
| Lidocaine + Guanfacine | Rescue Medication Use | 0.5 hours | 0 Participants |
| Lidocaine + Guanfacine | Rescue Medication Use | 1 hour | 1 Participants |
| Lidocaine + Guanfacine | Rescue Medication Use | 1.5 hours | 1 Participants |
| Lidocaine + Guanfacine | Rescue Medication Use | 2 hours | 0 Participants |
| Lidocaine + Guanfacine | Rescue Medication Use | 2.5 hours | 2 Participants |
| Lidocaine + Guanfacine | Rescue Medication Use | 3 hours | 3 Participants |
| Lidocaine + Guanfacine | Rescue Medication Use | 3.5 hours | 1 Participants |
p-value: 0.373Regression, Logistic
Secondary
Time to First Rescue Medication
Time, in hours, to use of first rescue medication in the follow-up period following the injection.
Time frame: 14 days
Population: Not all participants reported using rescue medication, so this analysis only includes participants that reported rescue medication use.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lidocaine Alone | Time to First Rescue Medication | 10.28 hours | Standard Deviation 23.54 |
| Lidocaine + Guanfacine | Time to First Rescue Medication | 23.76 hours | Standard Deviation 60.89 |