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

• Sponsor: Lynn Henry (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01921296
• Collaborator: Damon Runyon Cancer Research Foundation (Other)
• Enrollment: 2
• Location: 1
• Arm: 1
• Duration (Months): 20
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Sleep Initiation and Maintenance Disorders; Pain	Drug: Cyclobenzaprine	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 2 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Supportive Care
• 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
• Study Start Date: Aug 1, 2013
• Actual Primary Completion Date: May 1, 2014
• Actual Study Completion Date: Apr 1, 2015

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. 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 Outcome Measures

1. 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

2. 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109-0944

Sponsors and Collaborators

• Lynn Henry
• Damon Runyon Cancer Research Foundation

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Lynn Henry, Assistant Professor of Internal Med, University of Michigan Rogel Cancer Center
• ClinicalTrials.gov Identifier: NCT01921296
• Other Study ID Numbers: UMCC 2013.051
• First Posted: Aug 13, 2013
• Last Update Posted: Apr 20, 2016
• Last Verified: Mar 1, 2016

• Keywords provided by Lynn Henry, Assistant Professor of Internal Med, University of Michigan Rogel Cancer Center: Breast cancer; Aromatase inhibitor
• Additional relevant MeSH terms: Dyssomnias; Parasomnias; Sleep Initiation and Maintenance Disorders; Cyclobenzaprine

Study Results

Participant Flow

Arm/Group Title	Cyclobenzaprine
Arm/Group Description	Cyclobenzaprine (Flexeril) 5 milligrams orally 2 hours before bed, for a total of 24 weeks.
Period Title: Overall Study
STARTED	2
COMPLETED	2
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Cyclobenzaprine
Arm/Group Description	Cyclobenzaprine (Flexeril) 5 milligrams orally 2 hours before bed, for a total of 24 weeks.
Overall Participants	2
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	77.5
Sex: Female, Male (Count of Participants)
Female	2 100%
Male	0 0%

Outcome Measures

1. Primary Outcome

Title	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.
Description	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

Outcome Measure Data

Analysis Population Description

Only one of the two enrolled participants completed questionnaires after the baseline assessment

Arm/Group Title	Cyclobenzaprine
Arm/Group Description	Cyclobenzaprine (Flexeril) 5 milligrams orally 2 hours before bed, for a total of 24 weeks.
Measure Participants	1
Number [participant]	1

2. Secondary Outcome

Title	Change in Fatigue Between Baseline and Week 8 With Cyclobenzaprine Therapy
Description	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

Outcome Measure Data

Analysis Population Description

Only one of the two enrolled participants completed questionnaires after the baseline assessment

Arm/Group Title	Cyclobenzaprine
Arm/Group Description	Cyclobenzaprine (Flexeril) 5 milligrams orally 2 hours before bed, for a total of 24 weeks.
Measure Participants	1
Mean (Full Range) [change in T score]	1.3

3. Secondary Outcome

Title	Change in Average Pain Between Baseline and Week 8 With Cyclobenzaprine Therapy
Description	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

Outcome Measure Data

Analysis Population Description

Only one of the two enrolled participants completed questionnaires after the baseline assessment

Arm/Group Title	Cyclobenzaprine
Arm/Group Description	Cyclobenzaprine (Flexeril) 5 milligrams orally 2 hours before bed, for a total of 24 weeks.
Measure Participants	1
Mean (Full Range) [change in average pain]	-2

4. Other Pre-specified Outcome

Title	Percentage of Subjects Who Continue to Take Aromatase Inhibitor Therapy
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cyclobenzaprine
Arm/Group Description	Cyclobenzaprine (Flexeril) 5 milligrams orally 2 hours before bed, for a total of 24 weeks.
Measure Participants	2
Number [percentage of participants]	100 5000%

5. Other Pre-specified Outcome

Title	Percentage of Patients That Experience Adverse Events
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cyclobenzaprine
Arm/Group Description	Cyclobenzaprine (Flexeril) 5 milligrams orally 2 hours before bed, for a total of 24 weeks.
Measure Participants	2
Number [percentage of participants]	100 5000%

Adverse Events

Arm/Group Title	Cyclobenzaprine
Arm/Group Description	Cyclobenzaprine (Flexeril) 5 milligrams orally 2 hours before bed, for a total of 24 weeks.
All Cause Mortality
	Cyclobenzaprine
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Cyclobenzaprine
	Affected / at Risk (%)	# Events
Total	0/2 (0%)
Other (Not Including Serious) Adverse Events
	Cyclobenzaprine
	Affected / at Risk (%)	# Events
Total	2/2 (100%)
Metabolism and nutrition disorders
Hypercalcemia	1/2 (50%)	1
Nervous system disorders
Nervous System Disorder - Other	1/2 (50%)	1
Psychiatric disorders
Insomnia	2/2 (100%)	2

Limitations/Caveats

The study was closed early for futility. The primary endpoint was not analyzed.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.