Breast Cancer, Fatigue, Insomnia
Conditions
Keywords
Insomnia, Fatigue, QOL, CBT, Breast cancer, Survivors, Chemotherapy
Brief summary
This is a four-arm, randomized, controlled, clinical trial examining the efficacy of of cognitive behavioral therapy (CBT)-I and armodafinil in reducing insomnia in 226 female breast cancer patients who report sleep disturbances following completion of chemotherapy.
Detailed description
Treatment Protocol: CBT-I and armodafinil are being studied in a four-arm, randomized, controlled, clinical trial of 226 cancer survivors with chronic insomnia who are at least one month post treatment. The seven-week intervention is designed to determine the efficacy and acceptability of these treatment strategies in reducing insomnia in cancer survivors. Assessments will be made by questionnaires before, during, and two weeks following the study intervention. All ancillary treatments, as appropriate for control of symptoms caused by the cancer or its treatment may be administered as clinically indicated. Withdrawal of Sleep Medications: All participants, prior to beginning the baseline data collection phase of the study, must have withdrawn from all sleep medications, including: prescription, over-the-counter, CAM and herbal remedies for at least one week prior to beginning the study. CBT-I (Arms 3 & 4): CBT-I will be provided on an individual basis to all patients in study Arms 3 & 4 by a licensed clinical psychologist trained in CBT-I by Dr. Perlis. Subjects in these two study arms will receive 7 weeks of CBT-I, using a structured research grade protocol developed at the UR-SNRL. This manualized intervention, which exists as a published text: Perlis et al., 2005, includes four essential components: Sleep Restriction Therapy, Stimulus Control Instruction, Sleep Hygiene Guidelines, and a session of cognitive therapy. Data Collection: Patients will complete the Insomnia Severity (ISI) at the time of consent and every Friday during weeks 3-11 of the study. A follow-up call by study personnel will be made to each participant not currently receiving CBT-I on each of these Fridays to promote compliance, prompt completion, assess potential side effects of study medication, and answer patient questions.
Interventions
DRUGarmodafinil
Armodafinil P.O. daily/47 days (3-days at 50mg, then 40 days at 100mg, then 4 days at 50mg)
DRUGPlacebo Comparator
Placebo for 47 days
BEHAVIORALCBT-I
Seven weekly sessions of cognitive behavioral therapy for insomnia (CBT-I)
Sponsors
National Cancer Institute (NCI)
University of Rochester
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Have a diagnosis of cancer. 2. Be able to understand written and spoken English 3. Be able to swallow medication 4. Have preferred sleep phase between 7:30 pm and 11:00 am 5. Be willing to discontinue any medications/OTCs/Herbals for sleep for the 11-week study period 6. Be presumed to be in a state of cancer remission; use of tamoxifen, an aromatase inhibitor, and/or Herceptin is permitted 7. Self-report problems with insomnia for at least three months and that the insomnia began or got worse with the onset of cancer or treatment 8. Have completed chemotherapy and or radiation not less than one month ago. Note: Both types of treatment must be completed at least one month ago if patient receives chemotherapy and radiation therapy and there is no outer limit to how long ago treatments were completed.) 9. Report insomnia on the SDS-CL at a frequency of at least 3 days a week
Exclusion criteria
1. Have ever taken modafinil or had CBT-I therapy. CBT-I therapy for the sake of this protocol will be defined as any cognitive behavioral-based treatment for insomnia that includes a sleep restriction component. 2. Have an unstable medical or psychiatric illness (Axis I-current or within the last 5 years) 3. Have a history of seizures or severe headaches, or uncontrolled cardiac disease or hypertension 4. Be presently taking an anticoagulant or a corticosteroid 5. Have taken amphetamines (e.g., methylphenidate, pemoline \[Cylert®\] or similar psycho stimulants) within the past 30 days 6. Be currently pregnant or nursing 7. Have a history of substance abuse, or meet criteria for current alcohol abuse or dependence as assessed by a CAGE test score \>=2 or an Alcohol Use Disorders Identification Test (AUDIT) score \>=13 8. Have surgery planned within the study period 9. Have have ever been diagnosed with sleep apnea or have sleep apnea as indicated by endorsing either question 11 (I wake up choking or gasping for air) or question 12 (My bed partner has noticed that I seem to stop breathing) on the Sleep Disorders Symptom Check at the Often or Frequently level.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Insomnia Severity Index From Baseline to Post-intervention | ANCOVA was employed with multiple imputation on the post-intervention score (average of the two post-intervention weeks), controlling for the score at the time of consent (pre). | The Insomnia Severity Index (ISI) is a commonly used, 7-item psychometrically validated measure used to rate insomnia with 0-7 = absence of insomnia, 8-14 = subthreshold insomnia symptoms, 15-21 = moderate insomnia, and 22-28 = severe insomnia. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Fatigue Will be Assessed by the Total Score of the Revised Brief Fatigue Inventory (BFI) . | ANCOVA was employed with multiple imputation on the post-intervention score (average of the two post-intervention weeks), controlling for the score at the time of consent (pre). | The revised Brief Fatigue Inventory (BFI) is a 9-item, patient-report instrument with established reliability and validity. The BFI allows for the rapid assessment of fatigue level in cancer patients and identifies those patients with severe fatigue. Three items ask patients to rate their fatigue now, and fatigue at its worst and usual for the last 24 hours. The 11-point scales are bounded by 0 = no fatigue and 10 = fatigue as bad as you can imagine. Using the same type of scales, the remaining questions ask patients to rate how their fatigue interferes with several functional domains, including general activity, walking, mood, work, and relations with others. These scales are bounded by 0 = does not interfere and 10 = interferes completely. A global fatigue score (ranging from 0-10) can be obtained by averaging all the items on the BFI. |
Countries
United States
Participant flow
Recruitment details
138 Patients were consented of which 114 were eligible.
Pre-assignment details
18 Withdrew prior to randomization (3 ceased responding to contacts, 4 changed mind , 3 began or restarted sleep medication, 4 did not complete baseline measures, 1 did not receive approval from physician to participate, 1 found the diaries too much trouble, 1 did not want to take study medication, and 1 had a family emergency).
Participants by arm
| Arm | Count |
|---|---|
| 1 - CBT-I + Placebo CBT-I and placebo
Placebo Comparator: Placebo for 47 days
CBT-I: Seven weekly sessions of cognitive behavioral therapy for insomnia (CBT-I) | 24 |
| 2 - CBT-I + Armodafinil CBT-I + Armodafinil
armodafinil: Armodafinil P.O. daily/47 days (3-days at 50mg, then 40 days at 100mg, then 4 days at 50mg)
CBT-I: Seven weekly sessions of cognitive behavioral therapy for insomnia (CBT-I) | 23 |
| 3 - Placebo Only Placebo only
Placebo Comparator: Placebo for 47 days | 25 |
| 4 - Armodafinil Only Armodafinil only
armodafinil: Armodafinil P.O. daily/47 days (3-days at 50mg, then 40 days at 100mg, then 4 days at 50mg) | 24 |
| Total | 96 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Did not start intervention | 3 | 1 | 3 | 1 |
| Overall Study | resumed sleep medication | 0 | 0 | 1 | 2 |
| Overall Study | side-effects | 1 | 1 | 0 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 3 | 2 | 2 |
Baseline characteristics
| Characteristic | 1 - CBT-I + Placebo | 2 - CBT-I + Armodafinil | 3 - Placebo Only | 4 - Armodafinil Only | Total |
|---|---|---|---|---|---|
| Age, Continuous | 59 years STANDARD_DEVIATION 9.9 | 56 years STANDARD_DEVIATION 10.2 | 52 years STANDARD_DEVIATION 11.5 | 57 years STANDARD_DEVIATION 7.4 | 56.1 years STANDARD_DEVIATION 10 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 23 Participants | 22 Participants | 24 Participants | 22 Participants | 91 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 1 Participants | 2 Participants | 5 Participants |
| Gender Female | 21 Participants | 22 Participants | 18 Participants | 23 Participants | 84 Participants |
| Gender Male | 3 Participants | 1 Participants | 7 Participants | 1 Participants | 12 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 2 Participants | 4 Participants | 1 Participants | 8 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) White | 23 Participants | 21 Participants | 19 Participants | 23 Participants | 86 Participants |
| Region of Enrollment United States | 24 participants | 23 participants | 25 participants | 24 participants | 96 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 24 | 3 / 23 | 0 / 25 | 0 / 24 |
| serious Total, serious adverse events | 0 / 24 | 0 / 23 | 0 / 25 | 0 / 24 |
Outcome results
Primary
Change in Insomnia Severity Index From Baseline to Post-intervention
The Insomnia Severity Index (ISI) is a commonly used, 7-item psychometrically validated measure used to rate insomnia with 0-7 = absence of insomnia, 8-14 = subthreshold insomnia symptoms, 15-21 = moderate insomnia, and 22-28 = severe insomnia.
Time frame: ANCOVA was employed with multiple imputation on the post-intervention score (average of the two post-intervention weeks), controlling for the score at the time of consent (pre).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 - (CBT-I) + Placebo | Change in Insomnia Severity Index From Baseline to Post-intervention | -4.93 units on a scale | Standard Error 1.85 |
| 2 - CBT-I + Armodafinil | Change in Insomnia Severity Index From Baseline to Post-intervention | -6.36 units on a scale | Standard Error 1.84 |
| 3- Placebo Only | Change in Insomnia Severity Index From Baseline to Post-intervention | 1.04 units on a scale | Standard Error 1.89 |
| 4 - Armodafinil Only | Change in Insomnia Severity Index From Baseline to Post-intervention | -1.43 units on a scale | Standard Error 1.78 |
Secondary
Fatigue Will be Assessed by the Total Score of the Revised Brief Fatigue Inventory (BFI) .
The revised Brief Fatigue Inventory (BFI) is a 9-item, patient-report instrument with established reliability and validity. The BFI allows for the rapid assessment of fatigue level in cancer patients and identifies those patients with severe fatigue. Three items ask patients to rate their fatigue now, and fatigue at its worst and usual for the last 24 hours. The 11-point scales are bounded by 0 = no fatigue and 10 = fatigue as bad as you can imagine. Using the same type of scales, the remaining questions ask patients to rate how their fatigue interferes with several functional domains, including general activity, walking, mood, work, and relations with others. These scales are bounded by 0 = does not interfere and 10 = interferes completely. A global fatigue score (ranging from 0-10) can be obtained by averaging all the items on the BFI.
Time frame: ANCOVA was employed with multiple imputation on the post-intervention score (average of the two post-intervention weeks), controlling for the score at the time of consent (pre).
Population: Note: One patient randomized to the placebo only condition failed to provide data and was not included in the analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 - (CBT-I) + Placebo | Fatigue Will be Assessed by the Total Score of the Revised Brief Fatigue Inventory (BFI) . | 2.041 units on a scale | Standard Error 0.411 |
| 2 - CBT-I + Armodafinil | Fatigue Will be Assessed by the Total Score of the Revised Brief Fatigue Inventory (BFI) . | 1.209 units on a scale | Standard Error 0.364 |
| 3- Placebo Only | Fatigue Will be Assessed by the Total Score of the Revised Brief Fatigue Inventory (BFI) . | 2.971 units on a scale | Standard Error 0.534 |
| 4 - Armodafinil Only | Fatigue Will be Assessed by the Total Score of the Revised Brief Fatigue Inventory (BFI) . | 3.167 units on a scale | Standard Error 0.456 |