Pilot Study of Cyclobenzaprine for Treatment of Sleep Disturbance in Aromatase Inhibitor-treated Breast Cancer Patients

Study Overview
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Brief Summary
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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.

Official Title
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UMCC 2013.051: Prospective Pilot Study Evaluating the Use of Cyclobenzaprine for Treatment of Sleep Disturbance, Fatigue, and Musculoskeletal Symptoms in Aromatase Inhibitor-treated Breast Cancer Patients

Conditions
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Sleep Initiation and Maintenance Disorders, Pain

Intervention / Treatment
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* Drug: Cyclobenzaprine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cyclobenzaprine<br>Cyclobenzaprine (Flexeril) 5 milligrams orally 2 hours before bed, for a total of 24 weeks. | Drug: Cyclobenzaprine<br>* 5 milligrams orally 2 hours before bedtime<br>* Other names: Flexeril;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | baseline and 8 weeks | 
| 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. | baseline and 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breast cancer, Aromatase inhibitor