Erythromelalgia
Conditions
Brief summary
This research study is designed to investigate brain response using fMRI scan, and behavioral responses, to treatment with the drug carbamazepine (CBZ) in patients with the painful sodium channelopathy inherited Erythromelalgia (IEM). This study is designed to identify the central nervous system (CNS) regions that are activated during ongoing or evoked pain attacks, and the altered CNS response to CBZ treatment. This will advance our understanding of how IEM affects the brain. We also hope to validate a pharmacogenic approach to the study of IEM by use of an FDA approved drug. We hope, but cannot be sure, that subjects will directly benefit from this study.
Interventions
DRUGCarbamazepine
Day 1: Take 200 mg twice a day. Day 2: Take 200 mg twice a day. Day 3: Take 200 mg twice a day. Day 4: Take 200 mg twice a day. Day 5: Take 400 mg twice a day. Day 6: Take 400 mg twice a day. Day 7: Take 400 mg twice a day. Day 8: Take 400 mg twice a day. Day 9: Take 600 mg twice a day. Day 10: Take 600 mg twice a day. Day 11: Take 600 mg twice a day. Day 12: Take 600 mg twice a day. Day 13: Take 800 mg capsules twice a day. Day 14: Take 800 mg twice a day. Day 15: 800 mg twice a day. Day 16: Take 800 mg twice a day. Taper Down (After Visit 4 and 7) If maximal dose of 800 mg/day has been achieved, tapering down will take 9 days Taper down for 600 mg/day will take 6 days, and for 400 mg/day will take 3 days.
DRUGPlacebo
Sponsors
VA Connecticut Healthcare System
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* diagnosis/symptoms of EM * specific NaV1.7 sodium channel mutations (including S241T)
Exclusion criteria
* patients with no identified NaV1.7 mutation
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Carbamazepine Affects Pain in Patients With S241T NaV1.7 IEM Mutation | 15 days |
Secondary
| Measure | Time frame |
|---|---|
| Carbamazepine Affects Mean Duration of Pain Episode | 15 days |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Carbamazepine Then Placebo Administered in gradual doses from 100 mg twice a day increasing to no more than 400 mg twice a day if symptoms do not reduce. After 2 weeks of steady dose drug will be tapered down every 3 days.
Carbamazepine: Day 1: Take 200 mg twice a day. Day 2: Take 200 mg twice a day.
Day 3: Take 200 mg twice a day. Day 4: Take 200 mg twice a day. Day 5: Take 400 mg twice a day. Day 6: Take 400 mg twice a day. Day 7: Take 400 mg twice a day. Day 8: Take 400 mg twice a day. Day 9: Take 600 mg twice a day. Day 10: Take 600 mg twice a day. Day 11: Take 600 mg twice a day. Day 12: Take 600 mg twice a day. Day 13: Take 800 mg capsules twice a day. Day 14: Take 800 mg twice a day. Day 15: 800 mg twice a day. Day 16: Take 800 mg twice a day.
Taper Down (After Visit 4 and 7) If maximal dose of 800 mg/day has been achieved, tapering down will take 9 days Taper down for 600 mg/day will take 6 days, and for 400 mg/day will take 3 days. | 1 |
| Placebo the Carbamazepine Administered in gradual doses from 100 mg twice a day increasing to no more than 400 mg twice a day if symptoms do not reduce to match dosing with carbamazepine. After 2 weeks of steady dose drug will be tapered down every 3 days.
Placebo: Day 1: Take 200 mg twice a day. Day 2: Take 200 mg twice a day. Day 3: Take 200 mg twice a day. Day 4: Take 200 mg twice a day. Day 5: Take 400 mg twice a day. Day 6: Take 400 mg twice a day. Day 7: Take 400 mg twice a day. Day 8: Take 400 mg twice a day. Day 9: Take 600 mg twice a day. Day 10: Take 600 mg twice a day. Day 11: Take 600 mg twice a day. Day 12: Take 600 mg twice a day. Day 13: Take 800 mg capsules twice a day. Day 14: Take 800 mg twice a day. Day 15: 800 mg twice a day. Day 16: Take 800 mg twice a day.
Taper Down (After Visit 4 and 7) If maximal dose of 800 mg/day has been achieved, tapering down will take 9 days Taper down for 600 mg/day will take 6 days, and for 400 mg/day will take 3 days. | 1 |
| Total | 2 |
Baseline characteristics
| Characteristic | Carbamazepine Then Placebo | Placebo the Carbamazepine | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 1 Participants | 2 Participants |
| Erythromelalgia mutations S241T | 1 participants | 1 participants | 2 participants |
| Region of Enrollment United States | 1 participants | 1 participants | 2 participants |
| Sex: Female, Male Female | 0 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Male | 1 Participants | 0 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 2 | 0 / 2 |
| serious Total, serious adverse events | 0 / 2 | 0 / 2 |
Outcome results
Primary
Carbamazepine Affects Pain in Patients With S241T NaV1.7 IEM Mutation
Time frame: 15 days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Carbamazepine Then Placebo | Carbamazepine Affects Pain in Patients With S241T NaV1.7 IEM Mutation | Time in Pain Carbamazepine | 3015 minutes |
| Carbamazepine Then Placebo | Carbamazepine Affects Pain in Patients With S241T NaV1.7 IEM Mutation | Time in Pain Placebo | 6360 minutes |
| Placebo Then Carbamazepine | Carbamazepine Affects Pain in Patients With S241T NaV1.7 IEM Mutation | Time in Pain Carbamazepine | 136 minutes |
| Placebo Then Carbamazepine | Carbamazepine Affects Pain in Patients With S241T NaV1.7 IEM Mutation | Time in Pain Placebo | 915 minutes |
Secondary
Carbamazepine Affects Mean Duration of Pain Episode
Time frame: 15 days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Carbamazepine Then Placebo | Carbamazepine Affects Mean Duration of Pain Episode | Mean episode duration with Carbamazepine | 274.1 minutes |
| Carbamazepine Then Placebo | Carbamazepine Affects Mean Duration of Pain Episode | Mean episode duration with placebo | 615 minutes |
| Placebo Then Carbamazepine | Carbamazepine Affects Mean Duration of Pain Episode | Mean episode duration with Carbamazepine | 45.3 minutes |
| Placebo Then Carbamazepine | Carbamazepine Affects Mean Duration of Pain Episode | Mean episode duration with placebo | 91.5 minutes |