Trigeminal Neuralgia
Conditions
Brief summary
IncobotulinumtoxinA (Xeomin®) is a neurotoxin which inhibits the release of certain chemicals at the nerve terminals. It blocks cholinergic transmission at the neuromuscular junction by inhibiting the release of acetylcholine from motor neurons. In addition it blocks the release of Substance P (SP) and Calcitonin Gene Related Peptide (CGRP) from C fibers involved in pain perception. This study is designed to see if Xeomin® is superior to placebo in the treatment of medically refractory trigeminal neuralgia (TN). Subjects will be asked to maintain an attack diary throughout the study. They will also be asked to attend 4 office visits; Visit 1- Screening Visit, Visit 2- Injection Visit, Visit 3- Follow-Up Visit and Visit 4- Final Visit. At the end of the study the active (Xeomin®) and placebo groups will be compared to see if one group had better relief than the other.
Detailed description
This is a randomized, double-blind, placebo-controlled, add-on therapy study. Up to 70 eligible subjects with medically refractory TN will be screened to enroll forty subjects; twenty will be randomized to the active medication group IncobotulinumtoxinA (Xeomin) and twenty to the placebo group (0.9% Normal Saline Solution). Using a daily diary, all subjects will document their overall pain level and attack frequency and intensity for four weeks. After the four week baseline period, subjects will undergo initial injections (IncobotulinumtoxinA \[Xeomin\] or placebo). Subjects will remain on a consistent dose of their previously prescribed medications throughout the study. The primary outcome will be the difference in decrease in mean number of attacks of at least 4/10 intensity between the active and placebo groups. Secondary outcome measures will be frequency and average intensity of daily pain attacks. Subject Global Assessment, Beck Depression Inventory II (BDI-II), Short Form-36 (SF-36) Health Surveys, and visual analog scale (VAS), will also be assessed.
Interventions
BIOLOGICALIncobotulinumtoxina
Incobotulinumtoxina (Xeomin) is botulinum toxin type A and is administered via intramuscular injection.
OTHERPlacebo Comparator
Normal saline is sterile sodium chloride without and preservatives.
Sponsors
Merz North America, Inc.
Thomas Jefferson University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Inclusion Criteria * Age 18 - 75 yrs * Male or non-pregnant/non-lactating female * Subjects must have a mean attack frequency of at least 3 episodes/day of 4/10 pain * Use of adequate birth-control measures as determined by investigator for females of child-bearing potential * Diagnosis of Classical trigeminal neuralgia (TN) using International Classification of Headache Disorders (ICHD-2) criteria (see Appendix A in Protocol) * Subjects have given written informed consent prior to entering study * Subjects on a stable dose of concomitant preventive medications for treatment of TN for at least 4 weeks prior to study entry and throughout the 12 week observation period * Subjects who require rescue analgesic medication during the study will be allowed to use their current (pre-study) opioid and/or non opioid analgesics as clinically indicated (e.g., non-steroidal anti-inflammatory drugs (NSAIDs), acetaminophen, cyclooxygenase-2 (COX-2) inhibitors, topical analgesics). * Subjects will be prohibited from initiating any therapy with a new preventive medication throughout the remainder of the study. * Subject must be willing and able to abstain from initiating an alternative therapy (e.g., acupuncture, massage or physical therapy) for pain relief during the study. (NOTE: subjects who are currently using alternative therapy for pain relief can be enrolled if they are willing and able to maintain such therapy stable throughout the study.) \-
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Mean Number of Headache Attacks Reported in Active and Placebo Group | 84 days | Mean daily number of attacks during baseline period (30 days) will be compared to mean daily number of attacks for baseline and 84 days as recorded in patient diary. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Mean Pain Intensity of Active and Placebo Group | 84 days | Mean of the daily pain intensity as measured on a 0-10 pain scale where 0 = no pain and 10 is the worst pain reported on paper diary from baseline and 84 days |
Countries
United States
Participant flow
Recruitment details
The original target enrollment was 70 subjects
Pre-assignment details
Actual enrollment was 6. Recruitment efforts were limited to patients in our practice who could come in for visits and few responded to recruitment efforts. The appointment openings/schedule for visits was very limited.
Participants by arm
| Arm | Count |
|---|---|
| IncobotulinumtoxinA Xeomin 25-100 units injected to chosen area one time. | 3 |
| Placebo Comparator Placebo Comparator is 1-2 ml normal saline solution injected to chosen area one time. | 3 |
| Total | 6 |
Baseline characteristics
| Characteristic | IncobotulinumtoxinA | Total | Placebo Comparator |
|---|---|---|---|
| Age, Continuous | 54.3 years | 52.0 years | 49.6 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 6 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 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 | 1 Participants | 0 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 | 2 Participants | 5 Participants | 3 Participants |
| Region of Enrollment United States | 3 Participants | 6 Participants | 3 Participants |
| Sex: Female, Male Female | 2 Participants | 4 Participants | 2 Participants |
| Sex: Female, Male Male | 1 Participants | 2 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 3 |
| other Total, other adverse events | 2 / 3 | 3 / 3 |
| serious Total, serious adverse events | 0 / 3 | 0 / 3 |
Outcome results
Primary
Change in Mean Number of Headache Attacks Reported in Active and Placebo Group
Mean daily number of attacks during baseline period (30 days) will be compared to mean daily number of attacks for baseline and 84 days as recorded in patient diary.
Time frame: 84 days
Population: Patients treated with Xeomin and patients treated with placebo
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active | Change in Mean Number of Headache Attacks Reported in Active and Placebo Group | 1.96 attacks per day | Standard Deviation 2.9 |
| Placebo Group | Change in Mean Number of Headache Attacks Reported in Active and Placebo Group | -200.133 attacks per day | Standard Deviation 286.9 |
Secondary
Change in Mean Pain Intensity of Active and Placebo Group
Mean of the daily pain intensity as measured on a 0-10 pain scale where 0 = no pain and 10 is the worst pain reported on paper diary from baseline and 84 days
Time frame: 84 days
Population: Descriptive statistics only
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active | Change in Mean Pain Intensity of Active and Placebo Group | -2.66 units on a scale | Standard Deviation 0.98 |
| Placebo Group | Change in Mean Pain Intensity of Active and Placebo Group | .73 units on a scale | Standard Deviation 0.54 |