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

• ClinicalTrials.gov Identifier: NCT01921296
• Recruitment Status: Terminated
• First Posted: August 13, 2013
• Results First Posted: November 19, 2014
• Last Update Posted: April 20, 2016
• Sponsor: Lynn Henry
• Collaborator: Damon Runyon Cancer Research Foundation
• Information provided by (Responsible Party): Lynn Henry, University of Michigan Rogel Cancer Center

Tracking Information

• First Submitted Date: August 8, 2013
• First Posted Date: August 13, 2013
• Results First Submitted Date: November 12, 2014
• Results First Posted Date: November 19, 2014
• Last Update Posted Date: April 20, 2016
• Study Start Date: August 2013
• Actual Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 19, 2016)

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. [ Time Frame: 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.

Original Primary Outcome Measures (submitted: August 8, 2013)

Change in sleep quality between baseline and week 8 with cyclobenzaprine therapy [ Time Frame: 8 weeks ]

Will measure sleep quality using the Pittsburgh Sleep Quality Index at baseline and after 8 weeks of therapy with cyclobenzaprine.

Current Secondary Outcome Measures (submitted: March 21, 2016)

• Change in Fatigue Between Baseline and Week 8 With Cyclobenzaprine Therapy [ Time Frame: 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 [ Time Frame: 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.

Original Secondary Outcome Measures (submitted: August 8, 2013)

• Change in fatigue between baseline and week 8 with cyclobenzaprine therapy [ Time Frame: 8 weeks ]
  Will measure fatigue using the PROMIS fatigue questionnaire at baseline and after 8 weeks of therapy with cyclobenzaprine.
• Change in pain between baseline and week 8 with cyclobenzaprine therapy [ Time Frame: 8 weeks ]
  Will measure pain using the Brief Pain Inventory at baseline and after 8 weeks of therapy with cyclobenzaprine.

Current Other Pre-specified Outcome Measures (submitted: February 19, 2016)

• Percentage of Subjects Who Continue to Take Aromatase Inhibitor Therapy [ Time Frame: 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 [ Time Frame: 24 weeks ]
  Persistence with cyclobenzaprine therapy for 24 weeks will be assessed using a medication diary. Safety will be assessed using CTCAE criteria

Original Other Pre-specified Outcome Measures (submitted: August 8, 2013)

• Proportion of subjects who continue to take aromatase inhibitor therapy [ Time Frame: 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
• Safety and tolerability of cyclobenzaprine therapy [ Time Frame: 24 weeks ]
  Persistence with cyclobenzaprine therapy for 24 weeks will be assessed using a medication diary. Safety will be assessed using CTCAE criteria

Descriptive Information

• Brief Title: Pilot Study of Cyclobenzaprine for Treatment of Sleep Disturbance in Aromatase Inhibitor-treated Breast Cancer Patients
• Official Title: 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Supportive Care

Condition

• Sleep Initiation and Maintenance Disorders
• Pain

Intervention

Drug: Cyclobenzaprine

5 milligrams orally 2 hours before bedtime

Other Name: Flexeril

Study Arms

Experimental: Cyclobenzaprine

Cyclobenzaprine (Flexeril) 5 milligrams orally 2 hours before bed, for a total of 24 weeks.

Intervention: Drug: Cyclobenzaprine

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: May 19, 2014): 2
• Original Estimated Enrollment (submitted: August 8, 2013): 36
• Actual Study Completion Date: April 2015
• Actual Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01921296
• Other Study ID Numbers: UMCC 2013.051
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Lynn Henry, University of Michigan Rogel Cancer Center
• Original Responsible Party: University of Michigan Rogel Cancer Center
• Current Study Sponsor: Lynn Henry
• Original Study Sponsor: University of Michigan Rogel Cancer Center
• Collaborators: Damon Runyon Cancer Research Foundation

Investigators

• Principal Investigator: Norah L Henry, MD, PhD; University of Michigan

• PRS Account: University of Michigan Rogel Cancer Center
• Verification Date: March 2016