Cognitive Behavioral Therapy +/- Armodafinil for Insomnia and Fatigue Following Chemotherapy

Study Overview
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Brief Summary
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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
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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of Sleep Medications: All participants, prior to beginning the baseline data collection phase of the study, must have withdrawn from all sleep medications, including: prescription, over-the-counter, CAM and herbal remedies for at least one week prior to beginning the study.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.

Official Title
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Cognitive Behavioral Therapy +/- Armodafinil for Insomnia and Fatigue Following Chemotherapy

Conditions
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Insomnia, Fatigue, Breast Cancer

Intervention / Treatment
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* Drug: armodafinil
* Drug: Placebo Comparator
* Behavioral: CBT-I


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have a diagnosis of cancer. Be able to understand written and spoken English Be able to swallow medication Have preferred sleep phase between 7:30 pm and 11:00 am Be willing to discontinue any medications/OTCs/Herbals for sleep for the 11-week study period Be presumed to be in a state of cancer remission; use of tamoxifen, an aromatase inhibitor, and/or Herceptin is permitted 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 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.) Report insomnia on the SDS-CL at a frequency of at least 3 days a week Exclusion Criteria: 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. Have an unstable medical or psychiatric illness (Axis I-current or within the last 5 years) Have a history of seizures or severe headaches, or uncontrolled cardiac disease or hypertension Be presently taking an anticoagulant or a corticosteroid Have taken amphetamines (e.g., methylphenidate, pemoline [Cylert®] or similar psycho stimulants) within the past 30 days Be currently pregnant or nursing 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 Have surgery planned within the study period 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.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1 - CBT-I + placebo<br>CBT-I and placebo | Drug: Placebo Comparator<br>* Placebo for 47 days<br>Behavioral: CBT-I<br>* Seven weekly sessions of cognitive behavioral therapy for insomnia (CBT-I)<br>|
| Experimental: 2 - CBT-I + Armodafinil<br>CBT-I + Armodafinil | Drug: armodafinil<br>* Armodafinil P.O. daily/47 days (3-days at 50mg, then 40 days at 100mg, then 4 days at 50mg)<br>Behavioral: CBT-I<br>* Seven weekly sessions of cognitive behavioral therapy for insomnia (CBT-I)<br>|
| Placebo Comparator: 3 - Placebo only<br>Placebo only | Drug: Placebo Comparator<br>* Placebo for 47 days<br>|
| Experimental: 4 - Armodafinil only<br>Armodafinil only | Drug: armodafinil<br>* Armodafinil P.O. daily/47 days (3-days at 50mg, then 40 days at 100mg, then 4 days at 50mg)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Insomnia, Fatigue, QOL, CBT, Breast cancer, Survivors, Chemotherapy