Cognitive Behavioral Therapy and Multimodal Therapy in Treating Sleep Disturbance in Patients With Cancer

Sponsor

M.D. Anderson Cancer Center (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT01628029

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

Arms

113.4

Anticipated Duration (Months)

0.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This randomized phase II trial studies how well cognitive behavioral therapy and multimodal therapy works in treating sleep disturbance in patients with cancer. Cognitive behavioral therapy may help reduce sleep disturbances, fatigue, and insomnia as well as improve the well-being and quality of life of patients with cancer when given together with methylphenidate hydrochloride, therapeutic melatonin, and light therapy.

Condition or Disease	Intervention/Treatment	Phase
Hematopoietic and Lymphoid Cell Neoplasm Malignant Solid Neoplasm Sleep Disorder	Other: Counseling Drug: Methylphenidate Hydrochloride Procedure: Phototherapy Other: Placebo Administration Other: Quality-of-Life Assessment Procedure: Sham Intervention Drug: Therapeutic Melatonin	Phase 2

Detailed Description

PRIMARY OBJECTIVE:

To obtain preliminary estimates of the effects of cognitive behavioral therapy (CBT) and various treatments (light therapy, melatonin, methylphenidate [methylphenidate hydrochloride]) and combinations of treatments in multimodal therapy (MMT) in reducing sleep disturbance in patients with cancer, as measured by change in Pittsburgh Sleep Quality Index (PSQI) scores taken at baseline and on day 15.

SECONDARY OBJECTIVES:

To explore the effect of MMT on Insomnia Severity Index, cancer related symptoms (fatigue [Functional Assessment of Chronic Illness Therapy (FACIT-F) subscale, Edmonton Symptom Assessment System (ESAS)], anxiety, depression anxiety [Hospital Anxiety Depression Scale (HADS), ESAS]), quality of life (Functional Assessment of Cancer Therapy-General [FACT-G], ESAS), and physical activity/sleep efficacy (actigraphy), before and after treatment with various sleep disturbance (SD) treatment combinations of MMT.
To determine the safety of MMT (type, frequency, and severity of the adverse events).

OUTLINE: Patients are randomized to 1 of 8 treatment arms.

ARM I: Patients undergo CBT comprising 3 30-minute counseling sessions between baseline and day 14. Patients also receive methylphenidate hydrochloride orally (PO) twice daily (BID) and therapeutic melatonin PO once daily (QD), and undergo light therapy over 30 minutes for 15 days.

ARM II: Patients undergo CBT as in Arm I. Patients also receive methylphenidate placebo PO BID and melatonin placebo PO QD, and undergo sham light therapy over 30 minutes for 15 days.

ARM III: Patients undergo CBT as in Arm I. Patients also receive methylphenidate hydrochloride PO BID and therapeutic melatonin PO QD, and undergo sham light therapy over 30 minutes for 15 days.

ARM IV: Patients undergo CBT as in Arm I. Patients also receive methylphenidate hydrochloride PO BID and melatonin placebo PO QD, and undergo light therapy over 30 minutes for 15 days.

ARM V: Patients undergo CBT as in Arm I. Patients also receive methylphenidate placebo PO BID and therapeutic melatonin PO QD, and undergo light therapy over 30 minutes for 15 days.

ARM VI: Patients undergo CBT as in Arm I. Patients also receive methylphenidate placebo PO BID and melatonin placebo PO QD, and undergo light therapy over 30 minutes for 15 days.

ARM VII: Patients undergo CBT as in Arm I. Patients also receive methylphenidate hydrochloride PO BID and melatonin placebo PO QD, and undergo sham light therapy over 30 minutes for 15 days.

ARM VIII: Patients undergo CBT as in Arm I. Patients also receive methylphenidate placebo PO BID and therapeutic melatonin PO QD, and undergo sham light therapy over 30 minutes for 15 days.

Treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up on days 29 and 45.

Study Design

Study Type:

Interventional

Actual Enrollment :

68 participants

Allocation:

Randomized

Intervention Model:

Factorial Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Supportive Care

Official Title:

Multimodal Therapy for the Treatment of Sleep Disturbance in Patients With Cancer

Actual Study Start Date :

Jan 15, 2014

Anticipated Primary Completion Date :

Jun 30, 2023

Anticipated Study Completion Date :

Jun 30, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I (methylphenidate, melatonin, light therapy, CBT) Patients undergo CBT comprising 3 30-minute counseling sessions between baseline and day 14. Patients also receive methylphenidate hydrochloride PO BID and therapeutic melatonin PO QD, and undergo light therapy over 30 minutes for 15 days.	Other: Counseling Undergo CBT Other Names: Counseling Intervention Drug: Methylphenidate Hydrochloride Given PO Other Names: Concerta Quillivant XR Ritalin Procedure: Phototherapy Undergo light therapy Other Names: Actinotherapy Bright Light Therapy light therapy Other: Quality-of-Life Assessment Ancillary studies Other Names: Quality of Life Assessment Drug: Therapeutic Melatonin Given PO Other Names: Circadin Melatonin Melaxen
Experimental: Arm II (placebo, placebo, sham light therapy, CBT) Patients undergo CBT as in Arm I. Patients also receive methylphenidate placebo PO BID and melatonin placebo PO QD, and undergo sham light therapy over 30 minutes for 15 days.	Other: Counseling Undergo CBT Other Names: Counseling Intervention Other: Placebo Administration Given PO Other: Quality-of-Life Assessment Ancillary studies Other Names: Quality of Life Assessment Procedure: Sham Intervention Undergo sham light therapy Other Names: Sham Comparator
Experimental: Arm III (methylphenidate, melatonin, sham light therapy, CBT) Patients undergo CBT as in Arm I. Patients also receive methylphenidate hydrochloride PO BID and therapeutic melatonin PO QD, and undergo sham light therapy over 30 minutes for 15 days.	Other: Counseling Undergo CBT Other Names: Counseling Intervention Drug: Methylphenidate Hydrochloride Given PO Other Names: Concerta Quillivant XR Ritalin Other: Quality-of-Life Assessment Ancillary studies Other Names: Quality of Life Assessment Procedure: Sham Intervention Undergo sham light therapy Other Names: Sham Comparator Drug: Therapeutic Melatonin Given PO Other Names: Circadin Melatonin Melaxen
Experimental: Arm IV (methylphenidate, placebo, light therapy, CBT) Patients undergo CBT as in Arm I. Patients also receive methylphenidate hydrochloride PO BID and melatonin placebo PO QD, and undergo light therapy over 30 minutes for 15 days.	Other: Counseling Undergo CBT Other Names: Counseling Intervention Drug: Methylphenidate Hydrochloride Given PO Other Names: Concerta Quillivant XR Ritalin Procedure: Phototherapy Undergo light therapy Other Names: Actinotherapy Bright Light Therapy light therapy Other: Placebo Administration Given PO Other: Quality-of-Life Assessment Ancillary studies Other Names: Quality of Life Assessment
Experimental: Arm V (placebo, melatonin, light therapy, CBT) Patients undergo CBT as in Arm I. Patients also receive methylphenidate placebo PO BID and therapeutic melatonin PO QD, and undergo light therapy over 30 minutes for 15 days.	Other: Counseling Undergo CBT Other Names: Counseling Intervention Procedure: Phototherapy Undergo light therapy Other Names: Actinotherapy Bright Light Therapy light therapy Other: Placebo Administration Given PO Other: Quality-of-Life Assessment Ancillary studies Other Names: Quality of Life Assessment Drug: Therapeutic Melatonin Given PO Other Names: Circadin Melatonin Melaxen
Experimental: Arm VI (placebo, placebo, light therapy, CBT) Patients undergo CBT as in Arm I. Patients also receive methylphenidate placebo PO BID and melatonin placebo PO QD, and undergo light therapy over 30 minutes for 15 days.	Other: Counseling Undergo CBT Other Names: Counseling Intervention Procedure: Phototherapy Undergo light therapy Other Names: Actinotherapy Bright Light Therapy light therapy Other: Placebo Administration Given PO Other: Quality-of-Life Assessment Ancillary studies Other Names: Quality of Life Assessment
Experimental: Arm VII (methylphenidate, placebo, sham light therapy, CBT) Patients undergo CBT as in Arm I. Patients also receive methylphenidate hydrochloride PO BID and melatonin placebo PO QD, and undergo sham light therapy over 30 minutes for 15 days.	Other: Counseling Undergo CBT Other Names: Counseling Intervention Drug: Methylphenidate Hydrochloride Given PO Other Names: Concerta Quillivant XR Ritalin Other: Placebo Administration Given PO Other: Quality-of-Life Assessment Ancillary studies Other Names: Quality of Life Assessment Procedure: Sham Intervention Undergo sham light therapy Other Names: Sham Comparator
Experimental: Arm VIII (placebo, melatonin, sham light intervention, CBT) Patients undergo CBT as in Arm I. Patients also receive methylphenidate placebo PO BID and therapeutic melatonin PO QD, and undergo sham light therapy over 30 minutes for 15 days.	Other: Counseling Undergo CBT Other Names: Counseling Intervention Other: Placebo Administration Given PO Other: Quality-of-Life Assessment Ancillary studies Other Names: Quality of Life Assessment Procedure: Sham Intervention Undergo sham light therapy Other Names: Sham Comparator Drug: Therapeutic Melatonin Given PO Other Names: Circadin Melatonin Melaxen

Outcome Measures

Primary Outcome Measures

Change in Pittsburgh Sleep Quality Index (PSQI) score [Baseline up to day 29]
Estimates of treatment effects and combinations of treatment effects will be obtained by using standard linear regression techniques in which the change in PSQI values are regressed on indicator variables that represent treatment combinations that received 3 main effects for the primary treatments, 3 two-way interaction terms for each combination of two treatments, and 1 three-way interaction effects, which will be included in the linear regression model.

Secondary Outcome Measures

Change in Insomnia Severity Index scores [Baseline up to day 29]
Exploratory data analyses to examine associations between patients' change in PSQI score and the secondary measure of Insomnia Severity Index. Multivariate regression analyses will also be performed to determine the predictive relationship of this variable on PSQI and change in PSQI scores.
Change in Functional Assessment of Chronic Illness Therapy (FACIT)-F scores [Baseline up to day 29]
Exploratory data analyses to examine associations between patients' change in PSQI score and the secondary measure of FACIT-F scores. Multivariate regression analyses will also be performed to determine the predictive relationship of this variable on PSQI and change in PSQI scores.
Change in Hospital Anxiety Depression Scale (HADS) scores [Baseline up to day 29]
Exploratory data analyses to examine associations between patients' change in PSQI score and the secondary measure of HADS scores. Multivariate regression analyses will also be performed to determine the predictive relationship of this variable on PSQI and change in PSQI scores.
Change in Edmonton Symptom Assessment System (ESAS) scores [Baseline up to day 29]
Exploratory data analyses to examine associations between patients' change in PSQI score and the secondary measure of ESAS scores. Multivariate regression analyses will also be performed to determine the predictive relationship of this variable on PSQI and change in PSQI scores.
Change in actigraphy data [Baseline up to day 15]
Differences between participants receiving the MMT or the placebo treatment will be analyzed. This analysis will be based on fitting mixed effect linear models with actigraphy data as the response variables, and treatment intervention, demographic variables, and treatment site as independent variables.
Incidence of adverse events [Up to 45 days]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Cancer patients currently on cancer therapy with a positive screening for SD (screening PSQI score >= 5)
Patients should have a Zubrod =< 2
Patients with no pain and with stable pain (defined as pain under control and on stable doses of opioids for 1 week) are eligible
Memorial delirium assessment scale =< 13
Controlled pain and depression symptoms, if present (defined as no change in the morphine equivalent dose of 30% or change in the dose of antidepressant medication in the past 2 weeks)
All patients who are receiving chemotherapy and/or radiation therapy are eligible for study if they have completed > 1 week of radiation therapy, and if they have been approved to go on study by their primary oncologist; the principal investigator (PI)/designated research staff of this study will obtain and document approval from the primary oncologist and principal investigator of the clinical trial in case the patient is on another clinical trial as referenced in the patient's study documents
Serum creatinine =< 2.0 mg/dL
Total bilirubin =< 1.5 mg/dL
Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2 x upper limit of normal (ULN) or =< 5 x ULN if hepatic metastases are present
Patients on stable doses (defined as same dose for 2 weeks) of dexamethasone, mirtazapine, zolpidem, benzodiazepines, phenothiazines are allowed to participate in the study

Exclusion Criteria:

Have a major contraindication to methylphenidate (MP) (e.g., allergy/hypersensitivity to study medications or their constituents), light therapy (e.g., currently receiving ultraviolet A [UVA]/ultraviolet B [UVB] therapy), cognitive behavioral therapy (e.g., schizophrenia), or conditions making adherence difficult as determined by the attending physician
Currently taking MP or have taken it within the previous 10 days
Patients with a diagnosis of polysomnographically confirmed obstructive sleep apnea or narcolepsy
Regularly used cognitive behavioral therapy in the last 6 weeks for sleep disturbance
Unable to complete the baseline assessment forms or to understand the recommendations for participation in the study
Currently with a diagnosis of major depression, manic depressive disorder, obsessive-compulsive disorder, or schizophrenia)
Need monoamine oxidase inhibitors, tricyclic antidepressants, or clonidine
Have glaucoma
Symptomatic tachycardia and uncontrolled hypertension (determined to be clinically significant by the PI)
Currently receiving anticonvulsants (phenobarbital, diphenylhydantoin, primidone), phenylbutazone, clonidine, and/or tricyclic drugs (imipramine, clomipramine, or desipramine)
Unable to speak and understand English
Persons with congenital blindness and self-reported acquired blindness (independent of the cause) with no light perception
Patients with a history of retinal disease
Patients with > 2 hours of direct exposure to outdoor natural light per day by interview with the Study Coordinator
Patients with a diagnosis of obesity hypoventilation syndrome
Positive pregnancy test for women of childbearing potential, as defined by intact uterus and ovaries, and a history of menses within the last 12 months; pregnancy test to be performed no greater than 14 days prior to consent in study; in cases of women with elevated beta (b)-human chorionic gonadotropin (HCG), these candidates will be eligible to participate so long as the level of b-HCG is not consistent with pregnancy; women of childbearing potential need to be on or use contraception, or be abstinent during the study period; their male partners must also use contraception (condom) or maintain abstinence; birth control specifications: women who are able to become pregnant must use birth control during the study and for 30 days after
Women who are nursing
Patients who have taken melatonin within the past two weeks