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

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.

Study Overview

• Status: Recruiting
• Conditions: Depression; Cancer; Fatigue; Sleep; Anxiety
• Intervention / Treatment: Drug: Melatonin; Other: Placebo for Melatonin; Drug: Methylphenidate

Detailed Description

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), resting-state cognition (Amsterdam resting-state questionnaire, ARSQ) 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.

Exploratory:

To explore changes in brain function and structure (using functional, structural and diffusion-weighted MRI) and changes in resting-state cognition (ARSQ) and sleep symptoms following (a) combination therapy arm (i.e., CBT + BLT + MP + MT); (b) CBT + BLT + MT + placebo (MP); (c) CBT + MP + placebo (control light + MT); and (d) CBT + placebo (control light + MT + MP). We hypothesize that in patients with advanced cancer and sleep disturbances, there will be changes in (a) resting-state brain connectivity within the default-mode network; (b) cortical volume within specific brain areas including bilateral thalamus; and (c) white-matter water diffusion in specific fibers tracts that underline directed functional connectivity, including connectivity between the pulvinar, agranular frontal area and the parietal cortex - following (a-d) therapy arms; and (e) improvements in brain function and structure will be the most robust in combination therapy arm than placebo arm. We further hypothesize that improvements in brain function and structure will be associated with improvements in resting-state cognition and depressive symptoms.

• Study Type: Interventional
• Enrollment (Estimated): 188
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Sriram Yennu, MD; Phone Number: 713-792-6085; Email: syennu@mdanderson.org

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • MD Anderson Cancer Center
      • Contact: Sriram Yennu, MD; Phone Number: 713-792-6085; Email: syennu@mdanderson.org
      • Sub-Investigator: Sriram Yennu, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 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;
2. ability to communicate in English;
3. cognitively competent to respond appropriately to questions, as measured by the Memorial Delirium Assessment Scale (MDAS) (≤ 13/30);
4. willing and able to sign a written informed consent;
5. 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
6. 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:

1. active use of systemic anti-inflammatory prescription medications including steroids; unless used during or prior to cancer treatment as a prophylaxis (i.e., nausea);
2. 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.
3. Hospital Anxiety and Depression (HADS) score ≥21, or use of antidepressants, unless the patient is receiving a stable dose for at least 1 month;
4. use of hypnosedative drugs or stimulants; unless on stable doses of hypnosedative drugs or stimulants for at least 1 month;
5. use of monoamine oxidase inhibitors (MOI), tricyclic anti-depressants and anticoagulants; and
6. 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.
7. other medical reason that increases patient risk as determined by PI.

8. For patients participating in the MRI data collection component of the study, we will exclude the participants who meet the following criteria:

   1. . Pregnancy
   2. . Any metallic objects in the body. Metal plates, certain types of dental braces, cardiac pacemakers, ext., that are sensitive to electromagnetic fields contraindicate MRI scans
   3. . Claustrophobia

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Combination Therapy (BLT+MT+MP with CBT); 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; Given by PO; Other Names: Placebo for Methylphenidate Given by PO; Behavioral: Bright Light Therapy Given by PO; Behavioral: Cognitive Behavior Therapy Counseling session; Other: Placebo for Melatonin; Given by PO; Other Names: Placebo for Methylphendate Given by PO; Control Light Therapy Sham Therapy; behavioral: Cognitive Behavior Therapy Counseling session; Drug: Methylphenidate; Given by PO; Other Names: Control Light Therapy Sham Therapy; Behavioral: Cognitive Behavior Therapy Counseling session; Placebo for Melatonin Given by PO
Experimental: Placebo (CLT+ placebo MT + placebo MP with CBT); 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; Given by PO; Other Names: Placebo for Methylphenidate Given by PO; Behavioral: Bright Light Therapy Given by PO; Behavioral: Cognitive Behavior Therapy Counseling session; Other: Placebo for Melatonin; Given by PO; Other Names: Placebo for Methylphendate Given by PO; Control Light Therapy Sham Therapy; behavioral: Cognitive Behavior Therapy Counseling session
Experimental: Bright light and Melatonin (BLT + MT+ placebo MP with CBT); 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; Given by PO; Other Names: Placebo for Methylphendate Given by PO; Control Light Therapy Sham Therapy; behavioral: Cognitive Behavior Therapy Counseling session; Drug: Methylphenidate; Given by PO; Other Names: Control Light Therapy Sham Therapy; Behavioral: Cognitive Behavior Therapy Counseling session; Placebo for Melatonin Given by PO
Experimental: Methylphenidate (CLT + placebo MT + MP with CBT); 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; Given by PO; Other Names: Placebo for Methylphenidate Given by PO; Behavioral: Bright Light Therapy Given by PO; Behavioral: Cognitive Behavior Therapy Counseling session

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: M.D. Anderson Cancer Center
• Investigators: Principal Investigator: Sriram Yennu, MD, MD Anderson

Publications and helpful links

Helpful Links

• MD Anderson Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): November 21, 2022
• Primary Completion (Estimated): February 28, 2027
• Study Completion (Estimated): February 28, 2027

Study Registration Dates

• First Submitted: July 23, 2022
• First Submitted That Met QC Criteria: July 23, 2022
• First Posted (Actual): July 26, 2022

Study Record Updates

• Last Update Posted (Actual): April 22, 2024
• Last Update Submitted That Met QC Criteria: April 18, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Sleep Wake Disorders; Dyssomnias; Parasomnias; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Protective Agents; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Dopamine Agents; Dopamine Uptake Inhibitors; Antioxidants; Central Nervous System Stimulants; Melatonin; Methylphenidate
• Other Study ID Numbers: 2022-0180; NCI-2022-06045 (Other Identifier: NCI-CTRP Clinical Trials Reporting Registry)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No