Using melatonin to improve mood and sleep in bipolar disorder

Correcting Circadian Rhythms to Breakthrough in Bipolar Disorder

This study is testing if a low dose of melatonin, along with a sleep program, can help improve mood and sleep for people with bipolar disorder.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 50 (estimated)
• Ages: 18 Years to 60 Years
• Sex: All
• Sponsor: University of Michigan (Academic / other)
• Locations: 1 site (Ann Arbor, Michigan)
• Trial ID: NCT06226025 on ClinicalTrials.gov

What this trial studies

This study tests the effectiveness of low-dose melatonin combined with a behavioral sleep intervention to shift the brain's circadian clock earlier in individuals with bipolar disorder. Participants will be randomly assigned to receive either melatonin with the behavioral intervention or a placebo with a behavioral sleep placebo. The study aims to measure changes in sleep patterns and mood, specifically looking at the dim light melatonin onset and depressive symptoms. An open-label phase will allow previous placebo participants to receive the active treatment after completing the initial trial.

Who should consider this trial

Good fit: Ideal candidates are individuals diagnosed with bipolar disorder who have an evening chronotype and mild depressive symptoms.

Not a fit: Patients with bipolar disorder who do not have evening chronotype or are not experiencing depressive symptoms may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly improve mood and sleep quality for patients with bipolar disorder.

How similar studies have performed: Previous studies have shown promise in using melatonin for circadian rhythm disorders, but this specific combination approach is relatively novel.

Eligibility criteria

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.

Where this trial is running

Ann Arbor, Michigan

• University of Michigan — Ann Arbor, Michigan, United States (Recruiting)

Study contacts

• Principal investigator: Leslie Swanson, PhD — University of Michigan
• Study coordinator: Kelley DuBuc

Conditions Bipolar Disorder; Delayed Sleep-Wake Phase Disorder; Correcting Circadian Rhythms; Melatonin; Placebo; Dim light melatonin onset