Sleep Initiation and Maintenance Disorders, Pain
Conditions
Keywords
Breast cancer, Aromatase inhibitor
Brief summary
Many women with breast cancer who are treated with aromatase inhibitor medications develop difficulty sleeping and fatigue during treatment. Some examples of aromatase inhibitor medications include anastrozole (Arimidex), exemestane (Aromasin), and letrozole (Femara). Frequently, sleeping pills do not work very well to improve sleep. Cyclobenzaprine (Flexeril) is a medication that was originally developed to treat muscle spasms. It may also improve sleep in patients with chronic pain disorders, such as fibromyalgia. In this study we are testing to see if cyclobenzaprine at bedtime will help improve sleep in women treated with aromatase inhibitors.
Interventions
DRUGCyclobenzaprine
5 milligrams orally 2 hours before bedtime
Sponsors
Damon Runyon Cancer Research Foundation
Lynn Henry
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Female gender, age ≥ 18, postmenopausal. * Histologically proven stage 0-III invasive carcinoma of the breast * Initiating or have been receiving a standard dose of aromatase inhibitor therapy (letrozole 2.5mg once daily or exemestane 25mg once daily or anastrozole 1mg once daily) for up to a total of 48 months of AI therapy. * Trouble sleeping during the past week. (After signing the informed consent document, subjects must also have a global PSQI score of ≥5) * ECOG performance status 0-2 (see Appendix A).
Exclusion criteria
* Known hypersensitivity to cyclobenzaprine or any of the inactive ingredients * Diagnosis of sleep apnea that is currently interfering with sleep or requiring CPAP, restless leg syndrome that is currently interfering with sleep or requiring medication, or Epworth sleepiness scale \>10. * Subjects with a history of hypothyroidism must have been on a stable dose of thyroid replacement medicine for at least 3 months prior to enrollment * Treatment with steroids within 1 month * Treatment with monoamine oxidase inhibitors (MAO-I) within 14 days of enrollment. * Concurrent treatment with bupropion, MAO inhibitors, phenothiazines (including thioridazine), selegiline, tramadol, or medications known to prolong the QT interval (www.azcert.org/medical-pros/drug-lists/drug-lists.cfm) * Currently primary psychiatric diagnosis (schizophrenia, psychosis) or suicidal ideation, history of bipolar disorder, or seizure disorder * Known moderate or severe hepatic impairment * History of congestive heart failure or cardiac arrhythmia (other than atrial fibrillation); myocardial infarction within the past 6 months * Uncontrolled narrow-angle glaucoma * Pregnant or breast feeding * Serious or unstable medical condition that could likely lead to hospitalization during the course of the study or compromise study participation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients That Experience an Improvement in Sleep Quality as Assessed Using the Pittsburgh Sleep Quality Index (PSQI) With 8 Weeks of Cyclobenzaprine Therapy. | 8 weeks | Will measure sleep quality using the Pittsburgh Sleep Quality Index at baseline and after 8 weeks of therapy with cyclobenzaprine. A total score is calculated for the Pittsburgh Sleep Quality Index. The total score ranges from 0-21, with higher scores representing worse sleep quality. Any reduction in PSQI total score was considered an improvement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Fatigue Between Baseline and Week 8 With Cyclobenzaprine Therapy | baseline and 8 weeks | Will measure fatigue using the PROMIS fatigue questionnaire at baseline and after 8 weeks of therapy with cyclobenzaprine. The PROMIS Fatigue 7a score was calculated according to the information provided on the website. The raw score ranges from 7-35. The raw score is then converted to a T score according to the instruction on the website, with higher scores representing more fatigue. The T score rescales the raw score into a standardized score with a mean of 50 and a standard deviation of 10. The change in fatigue is calculated by subtracting the T score at baseline from the T score at 8 weeks. Positive values represent worsening of fatigue. |
| Change in Average Pain Between Baseline and Week 8 With Cyclobenzaprine Therapy | baseline and 8 weeks | Will measure average pain using the Brief Pain Inventory at baseline and after 8 weeks of therapy with cyclobenzaprine. On the Brief Pain Inventory, average pain is reported using a 0-10 scale, with higher numbers reflecting more pain. Change is calculated by subtracting pain at baseline is from pain at 8 weeks. A positive value represents an increase in pain. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects Who Continue to Take Aromatase Inhibitor Therapy | 24 weeks | We will assess the number of patients who continue to take the original aromatase inhibitor medication at the 24 week timepoint, as assessed using patient self-report and medical records |
| Percentage of Patients That Experience Adverse Events | 24 weeks | Persistence with cyclobenzaprine therapy for 24 weeks will be assessed using a medication diary. Safety will be assessed using CTCAE criteria |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cyclobenzaprine Cyclobenzaprine (Flexeril) 5 milligrams orally 2 hours before bed, for a total of 24 weeks. | 2 |
| Total | 2 |
Baseline characteristics
| Characteristic | Cyclobenzaprine |
|---|---|
| Age, Continuous | 77.5 years |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 2 / 2 |
| serious Total, serious adverse events | 0 / 2 |
Outcome results
Primary
Number of Patients That Experience an Improvement in Sleep Quality as Assessed Using the Pittsburgh Sleep Quality Index (PSQI) With 8 Weeks of Cyclobenzaprine Therapy.
Will measure sleep quality using the Pittsburgh Sleep Quality Index at baseline and after 8 weeks of therapy with cyclobenzaprine. A total score is calculated for the Pittsburgh Sleep Quality Index. The total score ranges from 0-21, with higher scores representing worse sleep quality. Any reduction in PSQI total score was considered an improvement.
Time frame: 8 weeks
Population: Only one of the two enrolled participants completed questionnaires after the baseline assessment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cyclobenzaprine | Number of Patients That Experience an Improvement in Sleep Quality as Assessed Using the Pittsburgh Sleep Quality Index (PSQI) With 8 Weeks of Cyclobenzaprine Therapy. | 1 participant |
Secondary
Change in Average Pain Between Baseline and Week 8 With Cyclobenzaprine Therapy
Will measure average pain using the Brief Pain Inventory at baseline and after 8 weeks of therapy with cyclobenzaprine. On the Brief Pain Inventory, average pain is reported using a 0-10 scale, with higher numbers reflecting more pain. Change is calculated by subtracting pain at baseline is from pain at 8 weeks. A positive value represents an increase in pain.
Time frame: baseline and 8 weeks
Population: Only one of the two enrolled participants completed questionnaires after the baseline assessment
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Cyclobenzaprine | Change in Average Pain Between Baseline and Week 8 With Cyclobenzaprine Therapy | -2 change in average pain |
Secondary
Change in Fatigue Between Baseline and Week 8 With Cyclobenzaprine Therapy
Will measure fatigue using the PROMIS fatigue questionnaire at baseline and after 8 weeks of therapy with cyclobenzaprine. The PROMIS Fatigue 7a score was calculated according to the information provided on the website. The raw score ranges from 7-35. The raw score is then converted to a T score according to the instruction on the website, with higher scores representing more fatigue. The T score rescales the raw score into a standardized score with a mean of 50 and a standard deviation of 10. The change in fatigue is calculated by subtracting the T score at baseline from the T score at 8 weeks. Positive values represent worsening of fatigue.
Time frame: baseline and 8 weeks
Population: Only one of the two enrolled participants completed questionnaires after the baseline assessment
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Cyclobenzaprine | Change in Fatigue Between Baseline and Week 8 With Cyclobenzaprine Therapy | 1.3 change in T score |
Other Pre-specified
Percentage of Patients That Experience Adverse Events
Persistence with cyclobenzaprine therapy for 24 weeks will be assessed using a medication diary. Safety will be assessed using CTCAE criteria
Time frame: 24 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cyclobenzaprine | Percentage of Patients That Experience Adverse Events | 100 percentage of participants |
Other Pre-specified
Percentage of Subjects Who Continue to Take Aromatase Inhibitor Therapy
We will assess the number of patients who continue to take the original aromatase inhibitor medication at the 24 week timepoint, as assessed using patient self-report and medical records
Time frame: 24 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cyclobenzaprine | Percentage of Subjects Who Continue to Take Aromatase Inhibitor Therapy | 100 percentage of participants |