Correcting Circadian Rhythms to Breakthrough in Bipolar Disorder

NCT ID: NCT06226025

Last Updated: 2025-10-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

50 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-08-13

Study Completion Date

2026-04-30

Brief Summary

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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.

Detailed Description

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Conditions

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Bipolar Disorder Delayed Sleep-Wake Phase Disorder

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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)
Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Outcome Assessors

Study Groups

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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.

Group Type EXPERIMENTAL

Melatonin

Intervention Type DRUG

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.

Behavioral sleep intervention

Intervention Type BEHAVIORAL

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

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.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

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 control

Intervention Type BEHAVIORAL

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.

Interventions

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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.

Intervention Type DRUG

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.

Intervention Type OTHER

Behavioral sleep intervention

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

Intervention Type BEHAVIORAL

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.

Intervention Type BEHAVIORAL

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Michigan

OTHER

Sponsor Role collaborator

Natrol

UNKNOWN

Sponsor Role collaborator

National Institute of Mental Health (NIMH)

NIH

Sponsor Role collaborator

Leslie Swanson

OTHER

Sponsor Role lead

Responsible Party

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Leslie Swanson

Associate Professor of Psychiatry

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Leslie Swanson, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Michigan

Locations

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University of Michigan

Ann Arbor, Michigan, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Kelley DuBuc

Role: CONTACT

734-764-2256

Facility Contacts

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Kelley DuBuc

Role: primary

734-764-2256

Other Identifiers

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1R21MH132901-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

HUM00235778

Identifier Type: -

Identifier Source: org_study_id

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