Recruiting
Phase 2

Circadian Rhythm

Sponsor:

Leslie Swanson

Code:

NCT06226025

Conditions

Bipolar Disorder

Delayed Sleep-Wake Phase Disorder

Eligibility Criteria

Sex: All

Age: 18 - 60

Healthy Volunteers: Not accepted

Interventions

Melatonin

Placebo

Behavioral sleep intervention

Behavioral sleep control

Study Details

Brief 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. 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.

Conditions

Bipolar Disorder

Delayed Sleep-Wake Phase Disorder

Study ID

NCT06226025

Start date

Aug 13, 2024

Status verified date

May, 2026

Completion date

Dec, 2026

Anticipated

Primary completion date

Dec, 2026

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 60

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
  • 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.

Study Design

Enrollment

50 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Melatonin

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.

placebo comparator: Placebo

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.

Interventions

Melatonin

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.

Placebo

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 intervention

An active intervention that is typically paired with melatonin to maximize treatment effects.

Behavioral sleep control

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.

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) ]

Central Contacts and Locations

Central contacts

Kelley DuBuc

734-764-2256dubuck@umich.edu

Locations

University of Michigan

Recruiting

Ann Arbor, Michigan, United States, 48109

Contacts

Kelley DuBuc

734-764-2256dubuck@umich.edu

Principal Investigator:

Leslie Swanson, PhD

More Information

Sponsor

Leslie Swanson

Last update posted

May 11, 2026

Last verified

May, 2026

Keywords

  • Correcting Circadian Rhythms
  • Melatonin
  • Placebo
  • Dim light melatonin onset

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Leslie Swanson on 2026-05-11.