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

Phase 2

Active, not recruiting

• Conditions: Sleep Disorder; Malignant Solid Neoplasm; Hematopoietic and Lymphoid Cell Neoplasm
• Interventions: Other: Counseling; Other: Placebo Administration; Drug: Methylphenidate Hydrochloride; Procedure: Phototherapy; Procedure: Sham Intervention; Other: Quality-of-Life Assessment; Drug: Therapeutic Melatonin

• Registration Number: NCT01628029
• Lead Sponsor: M.D. Anderson Cancer Center

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.

Detailed Description

PRIMARY OBJECTIVE:

I. 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:

I. 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.

II. 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 Timeline

• Study First Submitted: 2012-06-22
• Study First Submitted QC: 2012-06-25
• Study First Posted: 2012-06-26
• Study Start: 2014-01-15
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-11
• Last Update Posted: 2024-12-13
• Primary Completion: 2025-12-31
• Study Completion: 2025-12-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 68

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Arm I (methylphenidate, melatonin, light therapy, CBT)	Therapeutic Melatonin	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.
Arm III (methylphenidate, melatonin, sham light therapy, CBT)	Therapeutic Melatonin	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 VIII (placebo, melatonin, sham light intervention, CBT)	Therapeutic Melatonin	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.
Arm II (placebo, placebo, sham light therapy, CBT)	Placebo Administration	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 II (placebo, placebo, sham light therapy, CBT)	Counseling	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 V (placebo, melatonin, light therapy, CBT)	Counseling	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 I (methylphenidate, melatonin, light therapy, CBT)	Phototherapy	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.
Arm III (methylphenidate, melatonin, sham light therapy, CBT)	Counseling	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 (methylphenidate, placebo, light therapy, CBT)	Counseling	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 II (placebo, placebo, sham light therapy, CBT)	Sham Intervention	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 I (methylphenidate, melatonin, light therapy, CBT)	Counseling	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.
Arm I (methylphenidate, melatonin, light therapy, CBT)	Quality-of-Life Assessment	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.
Arm VII (methylphenidate, placebo, sham light therapy, CBT)	Placebo Administration	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 III (methylphenidate, melatonin, sham light therapy, CBT)	Quality-of-Life Assessment	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 V (placebo, melatonin, light therapy, CBT)	Quality-of-Life Assessment	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 (placebo, placebo, light therapy, CBT)	Phototherapy	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 VI (placebo, placebo, light therapy, CBT)	Quality-of-Life Assessment	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 (methylphenidate, placebo, sham light therapy, CBT)	Quality-of-Life Assessment	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 (placebo, melatonin, sham light intervention, CBT)	Sham Intervention	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.
Arm II (placebo, placebo, sham light therapy, CBT)	Quality-of-Life Assessment	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 (methylphenidate, melatonin, sham light therapy, CBT)	Sham Intervention	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 (methylphenidate, placebo, light therapy, CBT)	Placebo Administration	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 IV (methylphenidate, placebo, light therapy, CBT)	Quality-of-Life Assessment	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 VI (placebo, placebo, light therapy, CBT)	Counseling	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 VIII (placebo, melatonin, sham light intervention, CBT)	Counseling	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.
Arm IV (methylphenidate, placebo, light therapy, CBT)	Phototherapy	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 (placebo, melatonin, light therapy, CBT)	Phototherapy	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 V (placebo, melatonin, light therapy, CBT)	Placebo Administration	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 VII (methylphenidate, placebo, sham light therapy, CBT)	Counseling	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 (placebo, melatonin, sham light intervention, CBT)	Placebo Administration	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.
Arm V (placebo, melatonin, light therapy, CBT)	Therapeutic Melatonin	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 (placebo, placebo, light therapy, CBT)	Placebo Administration	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 VIII (placebo, melatonin, sham light intervention, CBT)	Quality-of-Life Assessment	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.
Arm VII (methylphenidate, placebo, sham light therapy, CBT)	Sham Intervention	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 I (methylphenidate, melatonin, light therapy, CBT)	Methylphenidate Hydrochloride	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.
Arm III (methylphenidate, melatonin, sham light therapy, CBT)	Methylphenidate Hydrochloride	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 (methylphenidate, placebo, light therapy, CBT)	Methylphenidate Hydrochloride	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 VII (methylphenidate, placebo, sham light therapy, CBT)	Methylphenidate Hydrochloride	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.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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 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 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.
Incidence of adverse events	Up to 45 days
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 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.

Trial Locations

Locations (1)

M D Anderson Cancer Center; 🇺🇸 Houston, Texas, United States