Bipolar DisorderPhase 2NCT06226025
Correcting Circadian Rhythms to Breakthrough in Bipolar Disorder
A Phase 2 study testing Melatonin and Behavioral sleep intervention in people with Bipolar Disorder and Delayed Sleep-Wake Phase Disorder, run by Leslie Swanson at 1 site in United States.
Trial summary
The purpose of this study is to test whether a dietary supplement (low-dose melatonin) commonly used to treat night owls, administered in conjunction with a behavioral sleep intervention, will help to shift the brain clock earlier and improve mood and sleep in bipolar disorder. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Bipolar Disorder, Delayed Sleep-Wake Phase Disorder
- What is being tested?
- Melatonin and Behavioral sleep intervention
- Type of treatment
- Pill or oral medicine, Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Aug 2024to Dec 2026
- Phase
- Phase 2
- 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 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Capable of giving informed consent
- Meet The Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria for bipolar disorder (BD) I or II
- Evening chronotype per the Morningness-Eveningness Questionnaire (MEQ) defined by a score of <42
- At least mild depressive symptoms on the Patient Health Questionnaire (PHQ)-9 defined by a score ≥5
- Psychotropic medications at stable dose for past month
- Able to download the MyDataHelps mobile application (app), and open app on participants' own phone
- Willing to abstain from alcohol for the duration of the intervention phase
- Female participants of childbearing potential (i.e., patients are not permanently sterilized (hysterectomy, bilateral salpingectomy, and bilateral oophorectomy) or postmenopausal (12 months with no menses without an alternative medical cause) by report) must agree to use a reliable method of contraception from the screening visit until 4 weeks after the study has completed.
Who cannot join
- Current diagnosis of, or high risk for, a sleep disorder other than DSPD per interview and medical record review (when available) including:
- Insomnia per DSM-5
- Sleep-disordered breathing per Snoring, tiredness, observed apnea, blood pressure, body mass index, age, neck circumference, and gender (STOP-BANG)
- Restless leg syndrome per sleep interview
- Narcolepsy
- Suspicion of vasomotor symptoms impacting sleep per interview for women that may be perimenopausal or postmenopausal.
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- Risk of current mania (per Young Mania Rating Scale (YMRS) score > 19).
- Suicidal or at high risk for suicide per Columbia Suicide Severity Rating Scale (C-SSRS) guidelines (i.e., presence of any suicidal behavior-suicide attempt, interrupted attempt, abort attempt, or preparatory behavior-in the past 3 months; and/or current active suicidal ideation with any intent), or as determined by the principal investigators.
- Presence of cardiac implantable electronic device, such as defibrillator or pacemaker.
- Presence of chronic psychiatric conditions which may directly influence sleep per interview and medical record review (when available), including:
- Current illicit drug use per the Drug Use Disorders Identification Test (DUDIT) defined by a score of ≥ 25
- Current alcohol or drug abuse per the Alcohol Use Disorder Identification Test (AUDIT) defined by a score of ≥ 16 and DUDIT
- Currently experiencing psychosis
- Presence of unstable chronic medical condition which may directly influence sleep:
- Chronic pain
- Thyroid conditions
- Current or history of medical conditions which may be affected by melatonin per self-report and medical record review (when available), such as:
- Hypertension or hypotension
- Diabetes Type 1 or Type 2
- Clotting/bleeding disorders
- Epilepsy/seizures
- Autoimmune disorders
- Conditions requiring immunosuppressive management such as transplant
- Per self-report or medical record review (when available), current use of medications which may have interactions with melatonin (see protocol for more details).
- Current use of medications that may interfere with the measurement of melatonin (non-steroidal anti-inflammatory drugs if used daily, and beta-blockers), per self-report and medical record review (when available).
- Self-report use of melatonin in the past month.
- Hypersensitivity to melatonin or any other component of the melatonin or placebo product.
- Pregnancy (as determined by dipstick urinary pregnancy test at screening for women of child-bearing potential) or self-report of breastfeeding and/or plan to become pregnant in the next 3 months.
- Self-report of routine night shift work.
- Self-report of past month travel or planned travel during the study across more than one time zone.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of Michigan
Ann Arbor, Michigan, 48109
Kelley DuBuc, 734-764-2256, dubuck@umich.edu
Leslie Swanson, PhD
About this study
The purpose of this study is to test whether a dietary supplement (low-dose melatonin) commonly used to treat night owls, administered in conjunction with a behavioral sleep intervention, will help to shift the brain clock earlier and improve mood and sleep in bipolar disorder. Eligible participants will be randomized to receive melatonin plus a behavioral sleep intervention or placebo plus a behavioral sleep placebo.
The hypotheses for this study include:
- Melatonin plus behavioral sleep intervention (compared to placebo plus behavioral sleep placebo) will produce a greater advance of dim light melatonin onset (DLMO), between pre- and post-treatment.
- Melatonin (compared to placebo) will produce a greater reduction in Patient Health Questionnaire-9 score between pre- and post-treatment.
- Being tested
- Melatonin, Placebo, Behavioral sleep intervention, Behavioral sleep control
- Keywords
- Correcting Circadian Rhythms, Melatonin, Placebo, Dim light melatonin onset
- Medical subject headings
- Bipolar Disorder, Sleep Disorders, Circadian Rhythm
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MelatoninDrug
Participants randomized to this intervention will take 1 oral pill (0.5 milligrams (mg)) daily. They will attend 4 weekly behavioral sleep intervention sessions with a therapist. In addition, participants will complete questionnaires (MyDataHelp app), monitor sleep, collect saliva samples, and wear the Fitbit Device.
PlaceboOther
Participants randomized to this intervention will take 1 oral placebo pill daily. They will attend 4 weekly behavioral sleep control sessions with a therapist. In addition, participants will complete questionnaires (MyDataHelp app), monitor sleep, collect saliva samples, and wear the Fitbit Device.
Behavioral sleep interventionBehavioural
An active intervention that is typically paired with melatonin to maximize treatment effects.
Behavioral sleep controlBehavioural
A behavioral placebo (which does not improve sleep in delayed sleep-wake phase disorder) to control for social/interpersonal effects of behavioral sleep intervention sessions.
| Study group | Role | What they receive |
|---|---|---|
| Melatonin | Experimental | Oral medication will be taken for 28 days on the afternoon or evening of the participants first intervention session and continue daily for the remainder of the treatment period. Receives: Drug: Melatonin; Behavioral: Behavioral sleep intervention |
| Placebo | Placebo comparator | Oral medication will be taken for 28 days on the afternoon or evening of the participants first intervention session and continue daily for the remainder of the treatment period. Receives: Other: Placebo; Behavioral: Behavioral sleep control |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in time of Dim Light Melatonin Onset (DLMO) baseline (pre-treatment) to 4 weeks (post-treatment)
Onset of melatonin in dim light conditions as measured in saliva (also called DLMO). Time of DLMO is measured in clock time and change in time of DLMO is measured in hours. The change score is calculated as time at 4 weeks minus baseline time. Thus, positive scores indicate a shift towards a later onset of melatonin and negative scores indicate a shift towards an earlier onset of melatonin.
Measured: 4 weeks (after treatment period)
Secondary outcomes (1)
Change in the Patient Health Questionnaire-9 (PHQ-9)
The PHQ-9 is a 9-item self-report scale to screen for symptoms of depression. Items are rated on a 4-point Likert scale from 0 (not at all) to 3 (nearly every day), with total scores ranging from 0 to 27, where higher scores indicate more severe depressive symptoms.
Measured: Baseline, 4 weeks (after treatment period)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jan 2024
- Study start13 Aug 2024
- Primary completionDec 2026 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Bipolar DisorderStudies of the same condition, open and under way.
- 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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants that meet eligibility for the randomized trial are randomized using minimization in a 1:1 ratio to low-dose afternoon melatonin plus a behavioral sleep intervention (MEL) or placebo tablet plus behavioral sleep placebo (CTL)
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Leslie Swanson
- Sponsor type
- University, hospital or other
- Collaborators
- University of Michigan, Natrol, National Institute of Mental Health (NIMH)
- Responsible party
- Sponsor-investigator, Leslie Swanson, University of Michigan
- Investigators
- Leslie Swanson, PhD, Principal investigator, University of Michigan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06226025
- Sponsor's protocol ID
- HUM00235778
- Other IDs
- 1R21MH132901-01A1
- Status last verified
- May 2026
- First submitted
- 16 Jan 2024
- Last updated
- 11 May 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Additional data collected as part of the study's fundings requirements per the National Institute of Mental Health to be shared to the National Institute of Mental Health Data Archive include the Generalized Anxiety-Disorder 7 item scale; World Health Organization Disability Assessment Schedule 2.0 scale, and the DSM-5 cross cutting assessment. Under the current protocol these data are to be collected to fulfill the National Institute of Mental Health funding requirements but are not included as endpoints or in our analytic plan.
Study at a glance
From the registry record, last updated by the sponsor on 11 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Correcting Circadian Rhythms to Breakthrough in Bipolar Disorder
- ClinicalTrials.gov ID
- NCT06226025
- Acronym / sponsor ID
- HUM00235778
- Keywords
- Correcting Circadian Rhythms, Melatonin, Placebo, Dim light melatonin onset
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Leslie SwansonUniversity, hospital or other
- Collaborators
- University of Michigan, Natrol, National Institute of Mental Health (NIMH)
- Study start
- 13 Aug 2024 (actual)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 26 Jan 2024 (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.
The purpose of this study is to test whether a dietary supplement (low-dose melatonin) commonly used to treat night owls, administered in conjunction with a behavioral sleep intervention, will help to shift the brain clock earlier and improve mood and sleep in bipolar disorder. Eligible participants will be randomized to receive melatonin plus a behavioral sleep intervention or placebo plus a behavioral sleep placebo.
The hypotheses for this study include:
- Melatonin plus behavioral sleep intervention (compared to placebo plus behavioral sleep placebo) will produce a greater advance of dim light melatonin onset (DLMO), between pre- and post-treatment.
- Melatonin (compared to placebo) will produce a greater reduction in Patient Health Questionnaire-9 score between pre- and post-treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
- Model description
- Participants that meet eligibility for the randomized trial are randomized using minimization in a 1:1 ratio to low-dose afternoon melatonin plus a behavioral sleep intervention (MEL) or placebo tablet plus behavioral sleep placebo (CTL)
| Arm | Type | Receives |
|---|---|---|
| Melatonin | Experimental | Drug: Melatonin, Behavioral: Behavioral sleep interventionOral medication will be taken for 28 days on the afternoon or evening of the participants first intervention session and continue daily for the remainder of the treatment period. |
| Placebo | Placebo comparator | Other: Placebo, Behavioral: Behavioral sleep controlOral medication will be taken for 28 days on the afternoon or evening of the participants first intervention session and continue daily for the remainder of the treatment period. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- Capable of giving informed consent
- Meet The Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria for bipolar disorder (BD) I or II
- Evening chronotype per the Morningness-Eveningness Questionnaire (MEQ) defined by a score of <42
- At least mild depressive symptoms on the Patient Health Questionnaire (PHQ)-9 defined by a score ≥5
- Psychotropic medications at stable dose for past month
Key exclusion criteria (30 listed)
- Current diagnosis of, or high risk for, a sleep disorder other than DSPD per interview and medical record review (when available) including:
- Risk of current mania (per Young Mania Rating Scale (YMRS) score > 19).
- Suicidal or at high risk for suicide per Columbia Suicide Severity Rating Scale (C-SSRS) guidelines (i.e., presence of any suicidal behavior-suicide attempt, interrupted attempt, abort attempt, or preparatory behavior-in the past 3 months; and/or current active suicidal ideation with any intent), or as determined by the principal investigators.
- Presence of cardiac implantable electronic device, such as defibrillator or pacemaker.
- Presence of chronic psychiatric conditions which may directly influence sleep per interview and medical record review (when available), including:
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 |
|---|---|---|
| MelatoninParticipants randomized to this intervention will take 1 oral pill (0.5 milligrams (mg)) daily. They will attend 4 weekly behavioral sleep intervention sessions with a therapist. In addition, participants will complete questionnaires (MyDataHelp app), monitor sleep, collect saliva samples, and wear the Fitbit Device. | Drug | Melatonin |
| PlaceboParticipants randomized to this intervention will take 1 oral placebo pill daily. They will attend 4 weekly behavioral sleep control sessions with a therapist. In addition, participants will complete questionnaires (MyDataHelp app), monitor sleep, collect saliva samples, and wear the Fitbit Device. | Other | Placebo |
| Behavioral sleep interventionAn active intervention that is typically paired with melatonin to maximize treatment effects. | Behavioural | Melatonin |
| Behavioral sleep controlA behavioral placebo (which does not improve sleep in delayed sleep-wake phase disorder) to control for social/interpersonal effects of behavioral sleep intervention sessions. | Behavioural | Placebo |
Primary outcome
Change in time of Dim Light Melatonin Onset (DLMO) baseline (pre-treatment) to 4 weeks (post-treatment)
Time frame: 4 weeks (after treatment period)
Onset of melatonin in dim light conditions as measured in saliva (also called DLMO). Time of DLMO is measured in clock time and change in time of DLMO is measured in hours. The change score is calculated as time at 4 weeks minus baseline time. Thus, positive scores indicate a shift towards a later onset of melatonin and negative scores indicate a shift towards an earlier onset of melatonin.
1 secondary outcome
Change in the Patient Health Questionnaire-9 (PHQ-9)
Time frame: Baseline, 4 weeks (after treatment period)
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 11 May 2026.
- Individual participant dataSharing planned: Yes. Additional data collected as part of the study's fundings requirements per the National Institute of Mental Health to be shared to the National Institute of Mental Health Data Archive include the Generalized Anxiety-Disorder 7 item scale; World Health Organization Disability Assessment Schedule 2.0 scale, and the DSM-5 cross cutting assessment. Under the current protocol these data are to be collected to fulfill the National Institute of Mental Health funding requirements but are not included as endpoints or in our analytic plan.
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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.
Leslie Swanson, PhD principal investigator
University of Michigan
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Melatonin and Behavioral sleep intervention in people with Bipolar Disorder and Delayed Sleep-Wake Phase Disorder, run by Leslie Swanson 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 30 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: looking for participants now, as of the sponsor's last update on 11 May 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this 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.
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?
Contact Kelley DuBuc (734-764-2256, dubuck@umich.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in time of Dim Light Melatonin Onset (DLMO) baseline (pre-treatment) to 4 weeks (post-treatment) (time frame: 4 weeks (after treatment period)). 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 11 May 2026.