SleepPhase 2/3NCT05474846
Combination Therapy for Treatment of Sleep Disturbance in Patients With Advanced Cancer
A Phase 2/3 study testing Melatonin and Methylphenidate in people with Sleep and Fatigue, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- What is being tested?
- Melatonin and Methylphenidate
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 169 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Nov 2022to 28 Feb 2027
- Phase
- Phase 2/3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
- Age 18 years or older
- be willing to complete in-person or telemedicine follow-up visits with research staff, and able to complete CBT intervention either in person or virtually within Texas.
Who cannot join
- 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.
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- other medical reason that increases patient risk as determined by PI.
- For patients participating in the MRI data collection component of the study, we will exclude the participants who meet the following criteria:
- . 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
- . Claustrophobia
- Pregnancy as documented in the medical record
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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.
- Conditions
- Sleep, Fatigue, Anxiety, Cancer, Depression
- Being tested
- Melatonin, Placebo for Melatonin, Methylphenidate
- Medical subject headings
- Fatigue, Anxiety Disorders, Neoplasms, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MelatoninDrug
Also called Methylphenidate Given by PO, Behavioral: Bright Light Therapy, Behavioral: Cognitive Behavior Therapy
Given by PO
Placebo for MelatoninOther
Also called Placebo for Methylphendate Given by PO, Control Light Therapy Sham Therapy, behavioral: Cognitive Behavior Therapy Counseling session
Given by PO
MelatoninDrug
Also called Placebo for Methylphenidate Given by PO, Behavioral: Bright Light Therapy Given by PO, Behavioral: Cognitive Behavior Therapy Counseling session
Given by PO
MethylphenidateDrug
Also called Placebo for Melatonin Given by PO, Control Light Therapy Sham Therapy, Behavioral: Cognitive Behavior Therapy Counseling session
Given by PO
| Study group | Role | What they receive |
|---|---|---|
| Combination Therapy (BLT+MT+MP with CBT) | Experimental | 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. Receives: Drug: Melatonin; Other: Placebo for Melatonin; Drug: Methylphenidate |
| Placebo (CLT+ placebo MT + placebo MP with CBT) | Experimental | 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. Receives: Drug: Melatonin; Other: Placebo for Melatonin |
| Bright light and Melatonin (BLT + MT+ placebo MP with CBT) | Experimental | 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. Receives: Other: Placebo for Melatonin; Drug: Methylphenidate |
| Methylphenidate (CLT + placebo MT + MP with CBT) | Experimental | 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. Receives: Drug: Melatonin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Through the study completion, an average of 1 year.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jul 2022
- Study start21 Nov 2022
- Primary completion28 Feb 2027 (estimated)
- Study completion28 Feb 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SleepStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 169 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Sriram Yennu, MD, Principal investigator, MD Anderson
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05474846
- Sponsor's protocol ID
- 2022-0180
- Other IDs
- NCI-2022-06045
- Status last verified
- Sep 2026
- First submitted
- 23 Jul 2022
- Last updated
- 25 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Combination Therapy for Treatment of Sleep Disturbance in Patients With Advanced Cancer
- ClinicalTrials.gov ID
- NCT05474846
- Acronym / sponsor ID
- 2022-0180
- Conditions
- Sleep, Fatigue, Anxiety, Cancer, Depression
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 169 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Study start
- 21 Nov 2022 (actual)
- Primary completion
- 28 Feb 2027 (estimated)
- Study completion
- 28 Feb 2027 (estimated)
- First posted
- 26 Jul 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Single blind (participant)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Combination Therapy (BLT+MT+MP with CBT) | Experimental | Drug: Melatonin, Other: Placebo for Melatonin, Drug: MethylphenidatePatients 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. |
| Placebo (CLT+ placebo MT + placebo MP with CBT) | Experimental | Drug: Melatonin, Other: Placebo for MelatoninPatients 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. |
| Bright light and Melatonin (BLT + MT+ placebo MP with CBT) | Experimental | Other: Placebo for Melatonin, Drug: MethylphenidatePatients 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. |
| Methylphenidate (CLT + placebo MT + MP with CBT) | Experimental | Drug: MelatoninPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MelatoninAlso: Methylphenidate Given by PO, Behavioral: Bright Light Therapy, Behavioral: Cognitive Behavior TherapyGiven by PO | Drug | Combination Therapy (BLT+MT+MP with CBT), Placebo (CLT+ placebo MT + placebo MP with CBT) |
| Placebo for MelatoninAlso: Placebo for Methylphendate Given by PO, Control Light Therapy Sham Therapy, behavioral: Cognitive Behavior Therapy Counseling sessionGiven by PO | Other | Bright light and Melatonin (BLT + MT+ placebo MP with CBT), Combination Therapy (BLT+MT+MP with CBT), Placebo (CLT+ placebo MT + placebo MP with CBT) |
| MelatoninAlso: Placebo for Methylphenidate Given by PO, Behavioral: Bright Light Therapy Given by PO, Behavioral: Cognitive Behavior Therapy Counseling sessionGiven by PO | Drug | Combination Therapy (BLT+MT+MP with CBT), Methylphenidate (CLT + placebo MT + MP with CBT) |
| MethylphenidateAlso: Placebo for Melatonin Given by PO, Control Light Therapy Sham Therapy, Behavioral: Cognitive Behavior Therapy Counseling sessionGiven by PO | Drug | Bright light and Melatonin (BLT + MT+ placebo MP with CBT), Combination Therapy (BLT+MT+MP with CBT) |
Primary outcome
Pittsburgh Sleep Quality Index (PSQI) questionnaires
Time frame: Through the study completion, an average of 1 year.
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).
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Sep 2026.
- MD Anderson Cancer CenterLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sriram Yennu, MD principal investigator
MD Anderson
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Melatonin and Methylphenidate in people with Sleep and Fatigue, run by M.D. Anderson Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 25 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pittsburgh Sleep Quality Index (PSQI) questionnaires (time frame: Through the study completion, an average of 1 year.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Sep 2026.