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

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

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.

Study Overview

• Status: Terminated
• Conditions: Pain; Sleep Initiation and Maintenance Disorders
• Intervention / Treatment: Drug: Cyclobenzaprine

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109-0944
      • University of Michigan Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cyclobenzaprine; Cyclobenzaprine (Flexeril) 5 milligrams orally 2 hours before bed, for a total of 24 weeks.	Drug: Cyclobenzaprine; 5 milligrams orally 2 hours before bedtime; Other Names: Flexeril

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	24 weeks
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	24 weeks

Collaborators and Investigators

• Sponsor: Lynn Henry
• Collaborators: Damon Runyon Cancer Research Foundation
• Investigators: Principal Investigator: Norah L Henry, MD, PhD, University of Michigan

Study record dates

Study Major Dates

• Study Start: August 1, 2013
• Primary Completion (Actual): May 1, 2014
• Study Completion (Actual): April 1, 2015

Study Registration Dates

• First Submitted: August 8, 2013
• First Submitted That Met QC Criteria: August 8, 2013
• First Posted (Estimate): August 13, 2013

Study Record Updates

• Last Update Posted (Estimate): April 20, 2016
• Last Update Submitted That Met QC Criteria: March 21, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Keywords: Breast cancer; Aromatase inhibitor
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Sleep Disorders, Intrinsic; Sleep Wake Disorders; Sleep Initiation and Maintenance Disorders; Dyssomnias; Parasomnias; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Tranquilizing Agents; Psychotropic Drugs; Antidepressive Agents; Antidepressive Agents, Tricyclic; Neuromuscular Agents; Muscle Relaxants, Central; Cyclobenzaprine
• Other Study ID Numbers: UMCC 2013.051