Neuropathic Pain
Conditions
Keywords
Pain, Neuropathic pain, Pain scores
Brief summary
This proposal is to conduct a double-blinded, randomized, placebo-controlled, crossover clinical study to examine the hypothesis that ramelteon would reduce pain score and improve functional status in subjects with neuropathic pain.
Detailed description
Neuropathic pain is a chronic pain condition resulting from injury to the peripheral and/or central nervous system. Despite extensive research over the last several decades, neuropathic pain remains poorly managed due to the lack of effective pharmacological tools. To date, little has been known regarding the effect of melatonin and its analogues on clinical neuropathic pain. We propose to conduct a randomized, placebo-controlled, double-blinded, and crossover clinical trial to examine the effect of ramelteon \[a melatonin (MT) 1/ MT2 receptor agonist\] on neuropathic pain. We hypothesize that ramelteon would reduce pain score and improve functional status in subjects with neuropathic pain.
Interventions
DRUGRamelteon
ramelteon (8 mg)
DRUGPlacebo
In a crossover design, a subject will be first assigned to the ramelteon or placebo arm and then switched over to the opposite arm.
Sponsors
Takeda Pharmaceuticals North America, Inc.
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Subject will be between ages 18 to 65 years. 2. Subject has not been on ramelteon for at least one month. 3. Subject agrees to make no change in his/her current pain medications during the entire study period (5 weeks). This requirement will ensure that valid comparisons of primary and secondary measures can be made before and after the study. 4. Subject has a VAS pain score of 5 or above at the beginning of the study. 5. Subject has had a neuropathic pain condition as listed above for at least three months. This requirement is to avoid clinical uncertainty from an unstable pain condition and to minimize the study variation. 6. Female subjects of childbearing potential must have a negative urine pregnancy test at the initial visit.
Exclusion criteria
1. Subject has moderate to severe liver impairment. 2. Subject has Liver Function Tests (LFT's) \>1.5X normal. 3. Subject has a history of renal impairment. 4. Subject has moderate or severe cardiac or pulmonary disease including a base line oxygen saturation of less than 95% on room air or any requirement for supplemental oxygen. 5. Subject has a history of glaucoma. 6. Subject has obstructive sleep apnea. 7. Subject is taking medications for sleep disorders including insomnia. 8. Subject has a major psychiatric disorder (major depression requiring a recent hospitalization within three months prior to the study; bipolar disorder; schizophrenia; psychotic disorders; substance abuse). 9. Subject has a history of dementia or delirium. 10. Subject has a history of falls. 11. Subject is pregnant or lactating. 12. Subject is using an illicit drug detected by a screening test. 13. Subject is currently taking Fluvoxamine. 14. Subject has been taking Ketoconazole in the past two weeks. 15. Subject has known hypersensitivity to ramelteon. 16. Subject has pending litigation related to his/her neuropathic pain condition. 17. Subject has Concurrent participation in other research drug trials or other study participation within 30 days of enrollment in this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Difference in Visual Analog Scale (VAS) for Pain (0-10) Between Treatments | VAS score at baseline and after the treatment period | Subjects were asked to rate their pain the VAS with 0 being no pain and 10 being the worst pain they can imagine. The VAS scores were compared between the baseline and after a period of treatment. A negative number indicates an improvement in pain from baseline score. |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited in person at the MGH Center for Pain or by advertisement throughout MGH and the local community.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Phase I; Ramelteon Phase II In a crossover design, a subject was first assigned to the placebo and then switched over to the ramelteon.
Ramelteon : ramelteon (8 mg) | 11 |
| Ramelton Phase I; Placebo Phase II In a crossover design, a subject was first assigned to the ramelteon and then switched over to the placebo.
Ramelteon : ramelteon (8 mg) | 12 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Phase I (14 Days) | Adverse Event | 0 | 1 |
| Phase I (14 Days) | Physician Decision | 1 | 2 |
| Phase I (14 Days) | Withdrawal by Subject | 1 | 1 |
| Phase II (14 Days) | Physician Decision | 0 | 1 |
| Washout (7 Days) | Physician Decision | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo Phase I; Ramelteon Phase II | Ramelton Phase I; Placebo Phase II | 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 | 11 Participants | 12 Participants | 23 Participants |
| Region of Enrollment United States | 11 Participants | 12 Participants | 23 Participants |
| Sex: Female, Male Female | 7 Participants | 5 Participants | 12 Participants |
| Sex: Female, Male Male | 4 Participants | 7 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 23 | 0 / 23 |
| serious Total, serious adverse events | 1 / 23 | 0 / 23 |
Outcome results
Primary
Difference in Visual Analog Scale (VAS) for Pain (0-10) Between Treatments
Subjects were asked to rate their pain the VAS with 0 being no pain and 10 being the worst pain they can imagine. The VAS scores were compared between the baseline and after a period of treatment. A negative number indicates an improvement in pain from baseline score.
Time frame: VAS score at baseline and after the treatment period
Population: Only 15 subjects completed both treatment phases so we only included these subjects in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ramelteon | Difference in Visual Analog Scale (VAS) for Pain (0-10) Between Treatments | -1.0 units on a scale | Standard Deviation 1.4 |
| Placebo | Difference in Visual Analog Scale (VAS) for Pain (0-10) Between Treatments | -1.1 units on a scale | Standard Deviation 1.5 |
p-value: >0.05t-test, 2 sided