Insomnia Due to Medical Condition, Chronic Pain
Conditions
Keywords
Insomnia, Chronic Pain, Gabapentin, Tizanidine, Placebo
Brief summary
This is a double-blind, placebo-controlled, randomized, crossover trial aimed at assessing the effect of gabapentin and tizanidine, two pain medications, on insomnia in chronic pain patients.
Detailed description
Chronic pain and insomnia are highly prevalent conditions affecting 10-25% and 6-10% of the general population, respectively. Importantly, these two conditions frequently co-occur, with 50-80% of chronic pain patients reporting sleep disturbances. Identifying medication that alleviates pain and insomnia simultaneously may help reduce risks associated with polypharmacy, including drug-drug interactions. In this double-blind, placebo-controlled, randomized, crossover trial, gabapentin and tizanidine, two drugs which are respectively commonly used to treat neuropathic and musculoskeletal pain, will be compared to each other and to placebo in their ability to alleviate insomnia in chronic pain patients. In each week, patients will receive 3-night (Friday-Sunday) trials each of placebo, gabapentin or tizanidine in a randomized, double-blind order and will monitor their insomnia using the Athens Insomnia Scale (AIS) questionnaire (adapted to fit the time frame of this trial). The primary outcome consists of the difference in mean AIS scores between the 3 treatments at the primary time point, which is Monday of each week (after 3 nights of drug intake). Patients will also monitor their sleepiness, pain relief and overall improvement as secondary variants using the Stanford Sleepiness Scale (SSS), Visual Analog Scale (VAS), and Patient's Global Impression of Change (PGIC) questionnaires respectively. Scores on the Monday preceding the first treatment will serve as baseline and the period between treatments (i.e. Monday-Thursday nights) will serve as a 4-day washout period between treatments. Our hypothesis is that gabapentin and tizanidine will both be more effective than placebo in alleviating insomnia in chronic pain patients but will not be different from one another.
Interventions
DRUGGabapentin
Friday night: 1 capsule of 300 mg, Saturday night: 2 capsule of 300 mg (total 600 mg), Sunday night: choice of 1 or 2 capsule of 300 mg (total of 300 or 600 mg)
DRUGPlacebo
Friday night: 1 capsule, Saturday night: 2 capsule, Sunday night: choice of 1 or 2 capsules
DRUGTizanidine
Friday night: 1 capsule of 2 mg, Saturday night: 2 capsule of 2 mg (total 4 mg), Sunday night: choice of 1 or 2 capsules of 2 mg (total of 2 or 4 mg)
Sponsors
National Center for Advancing Translational Sciences (NCATS)
University of California, San Diego
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Each participant will have an identification number and randomization of drug sequence allocation will be performed a priori using a random number generator by the study pharmacist. The 3 treatments will be identically encapsulated by the study pharmacist. The study pharmacist will place the drug capsules in identical sealed plastic bags labeled Treatment 1 through Treatment 3.
Intervention model description
Randomized, Double-bind, Placebo-controlled, Crossover Trial
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* BMI ≤ 35 * Any ethnicity * Must be able to communicate in English * Must have access to email and be able to respond to REDCap questionnaires in English * Has a chronic pain condition (≥ 3 months of pain) * Reports sleep disturbance and scores ≥ 6 on AIS questionnaire * Ability to provide informed consent
Exclusion criteria
* Pregnancy * Breastfeeding * Has diagnosis of chronic kidney disease * Has known QT prolongation \>500 msec on prior EKG * Inability to complete daily questionnaires * Allergy to, or intolerance of, any of tizanidine or gabapentin * Shift workers * Anticipated travel across multiple time zones (jetlag) during the duration of the trial * Circadian misalignment * Prior syncope experience and/or fear of blood/needles (if a blood draw is required)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sleep quality | Monday after 3 nights of drug intake | Comparison of group means for Athens Insomnia Scale scores between the 3 treatment groups placebo, gabapentin and tizanidine. Total Athens Insomnia Scale score ranges from 0 to 24. The higher the score, the more severe the insomnia symptoms experienced by the patient. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pain Intensity | Monday after 3 nights of drug intake | Comparison of group means for Visual Analog Scale scores between the 3 treatment groups placebo, gabapentin and tizanidine. Visual Analog Scale score ranges from 0 to 10. The higher the score, the worse the pain experienced by the patient. |
| Alertness | Monday after 3 nights of drug intake | Comparison of group means for Stanford Sleepiness Scale scores between the 3 treatment groups placebo, gabapentin and tizanidine. Stanford Sleepiness Scale score ranges from 1 to 7. The higher the score, the more sleepy and less alert the patient. |
| Overall improvement | Monday after 3 nights of drug intake | Comparison of group means for Patient Global Impression of Change scores between the 3 treatment groups placebo, gabapentin and tizanidine. Patient Global Impression of Change score ranges from 1 to 7. The higher the score, the more improvement reported by the patient. |
| Categorical assessment of insomnia improvement | Monday after 3 nights of drug intake | Percentage of patients with a 30% improvement from baseline in individual Athens Insomnia Scale scores for each of the 3 treatments placebo, gabapentin and tizanidine. Total Athens Insomnia Scale score ranges from 0 to 24. The higher the scores, the more severe the insomnia symptoms experienced by the patient. |
Countries
United States
Outcome results
None listed