Combination Therapy for Treatment of Sleep Disturbance in Patients With Advanced Cancer

Study Overview
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Brief Summary
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To learn if Cognitive Behavior Therapy (called CBT), combined with either Bright Light Therapy (called BLT), methylphenidate, and/or melatonin, can help improve sleep and other related symptoms such as fatigue, anxiety, and depression in cancer patients. This is an investigational study. In this study, BLT, Methylphenidate and Melatonin will be compared to their placebos.

Detailed Description
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Objectives: Primary: To compare the effects of the combination therapy arm with the placebo arm on sleep quality as assessed by the Pittsburgh Sleep Quality Index (PSQI) at the end of 6 weeks (primary end point). We hypothesize that there will be a greater maintenance of sleep quality in the combination arm than in the placebo arm after 6 weeks. Secondary: To compare the effects of the combination therapy arm with the placebo arm on sleep quality (PSQI) at 3- and 6-months post-intervention. We hypothesize that there will be a greater maintenance of sleep quality in the combination arm than in the placebo arm at 3- and 6-months post intervention. Secondary: To compare the effects of the remaining active therapy arms with the placebo and combination arms on sleep quality (PSQI) at all post-intervention assessments. We hypothesize that there will be a greater maintenance of sleep quality in the active arms than in the placebo arm at all post-intervention assessments. Additionally, there will be greater maintenance of sleep quality in the combination arm than in the remaining active arms. Secondary: To compare the effects of the active therapy arm and the placebo arm for sleep-wake cycle disturbance (Actigraphy - sleep onset latency, wake after sleep onset, total sleep time, sleep efficiency, and mean daytime activity). We hypothesize that there w/ill be greater maintenance of sleep-wake cycle (synchronization) in the combination therapy arm. Secondary: To determine whether the addition of MP to BLT+MT synergistically maintains sleep quality as measured by change from baseline PSQI. We hypothesize that MP and BLT+MT will synergistically maintain sleep quality. Exploratory: To explore the effects of the active therapy arm on psychological symptoms (Hospital Anxiety and Depression Scale), fatigue (Functional Assessment of Chronic Illness Therapy - Fatigue), sleep and related symptoms (PROMIS-Sleep), inflammation (C-reactive protein), and quality of life (Functional Assessment of Cancer Therapy - General) and how they vary over time. We hypothesize that there will be more promotion of sleep related symptoms and quality of life in the combination therapy arm than in the placebo, BLT, and Methylphenidate arms.

Official Title
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Combination Therapy for Treatment of Sleep Disturbance in Patients With Advanced Cancer

Conditions
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Sleep, Fatigue, Anxiety, Cancer, Depression

Intervention / Treatment
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* Drug: Melatonin
* Other: Placebo for Melatonin
* Drug: Melatonin
* Drug: Methylphenidate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: presence of poor sleep quality, defined as Pittsburgh Sleep Quality Index (PSQI) total score ≥ 5, with patients describing poor sleep as being present for a minimum of 2 weeks; ability to communicate in English; cognitively competent to respond appropriately to questions, as measured by the Memorial Delirium Assessment Scale (MDAS) (≤ 13/30); willing and able to sign a written informed consent; life expectancy of ≥ 1 year as assessed by the oncologist or the principal investigator (SY) using the surprise question, Would I be surprised if this patient died in the next 12 months?; and no pain or stable pain (defined as pain ≤ 4 on Edmonton Symptom Assessment Scale (ESAS) or under control and on stable doses of opioids for 1 month). Exclusion Criteria: active use of systemic anti-inflammatory prescription medications including steroids; unless used during or prior to cancer treatment as a prophylaxis (i.e., nausea); known history of psychiatric illness (e.g., schizophrenia, bipolar disorder, major depressive disorder), sleep disorder (e.g., obstructive sleep apnea, narcolepsy, periodic limb movement disorder), obesity hypoventilation syndrome, glaucoma, congenital blindness, self-reported acquired blindness, significant cataracts or retinal disease; and night shift workers. Hospital Anxiety and Depression (HADS) score ≥21, or use of antidepressants, unless the patient is receiving a stable dose for at least 1 month; use of hypnosedative drugs or stimulants; unless on stable doses of hypnosedative drugs or stimulants for at least 1 month; use of monoamine oxidase inhibitors (MOI), tricyclic anti-depressants and anticoagulants; and patients who have bright sunlight exposure for consecutive 30 minutes or more daily in the past month, or prior exposure to BLT, or prior use of MT, MP, or CBT.

Ages Eligible for Study
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Minimum Age: 18 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: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Combination Therapy (BLT+MT+MP with CBT)<br>Patients receive Melatonin (called MT) PO QD for 6 weeks, Methylphenidate (called MP) PO BID for 6 weeks, Bright Light Therapy (called BLT) for 30 minutes daily for 6 weeks, and Cognitive Behavior Therapy (called CBT) weekly for 6 weeks. | Drug: Melatonin<br>* Given by PO<br>* Other names: Behavioral: Cognitive Behavior Therapy;Other: Placebo for Melatonin<br>* Given by PO<br>* Other names: behavioral: Cognitive Behavior Therapy Counseling session;Drug: Melatonin<br>* Given by PO<br>* Other names: Behavioral: Cognitive Behavior Therapy Counseling session;Drug: Methylphenidate<br>* Given by PO<br>* Other names: Behavioral: Cognitive Behavior Therapy Counseling session;|
| Experimental: Placebo (CLT+ placebo MT + placebo MP with CBT)<br>Patients receive placebo Melatonin (called placebo MT) PO QD for 6 weeks, placebo Methylphenidate (called placebo MP) PO BID for 6 weeks, Control Light Therapy (called CLT) for 30 minutes daily for 6 weeks and Cognitive Behavior Therapy (called CBT) weekly for 6 weeks. | Drug: Melatonin<br>* Given by PO<br>* Other names: Behavioral: Cognitive Behavior Therapy;Other: Placebo for Melatonin<br>* Given by PO<br>* Other names: behavioral: Cognitive Behavior Therapy Counseling session;|
| Experimental: Bright light and Melatonin (BLT + MT+ placebo MP with CBT)<br>Patients receive Bright Light Therapy (called BLT) for 30 minutes daily for 6 weeks, Melatonin (called MT) PO QD for 6 weeks, placebo Methylphenidate (called placebo MP) PO BID for 6 weeks, and Cognitive Behavior Therapy (called CBT) weekly for 6 weeks. | Other: Placebo for Melatonin<br>* Given by PO<br>* Other names: behavioral: Cognitive Behavior Therapy Counseling session;Drug: Methylphenidate<br>* Given by PO<br>* Other names: Behavioral: Cognitive Behavior Therapy Counseling session;|
| Experimental: Methylphenidate (CLT + placebo MT + MP with CBT)<br>Patients receive Control Light Therapy (called CLT) for 30 minutes daily for 6 weeks, placebo Melatonin (called placebo MT) PO QD for 6 weeks, Methylphenidate (called MP) PO BID for 6 weeks, and Cognitive Behavior Therapy (called CBT) weekly for 6 weeks. | Drug: Melatonin<br>* Given by PO<br>* Other names: Behavioral: Cognitive Behavior Therapy Counseling session;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pittsburgh Sleep Quality Index (PSQI) questionnaires | Pittsburgh Sleep Quality Index (PSQI) questionnaire score on a 4-point scale ranging from 0 (not during the 2 weeks) to 3 (3 or more times a week). | Through the study completion, an average of 1 year. |