Clinical trial NCT06226025: Correcting Circadian Rhythms to Breakthrough in Bipolar Disorder
Official title: Correcting Circadian Rhythms to Breakthrough in Bipolar Disorder
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Bipolar Disorder
Delayed Sleep-Wake Phase Disorder
Keywords: Correcting Circadian Rhythms
Melatonin
Placebo
Dim light melatonin onset
Lead sponsor: University of Michigan
Sponsor class: OTHER
Collaborators: name: University of Michigan
name: Natrol
name: National Institute of Mental Health (NIMH)
First posted: 2024-01-26
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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)

After the Randomized clinical trial portion, ten participants from the control group will be recruited to receive open label melatonin.
Primary purpose: TREATMENT

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.

Detailed description: Ten Participants that competed the randomized trial and were assigned to the placebo group (and meet eligibility) can participate in the open label part of this project. Participants will sign a separate consent for this open label part.

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.

Primary outcomes:
measure: Change in time of Dim Light Melatonin Onset (DLMO) baseline (pre-treatment) to 4 weeks (post-treatment)
timeFrame: 4 weeks (after treatment period)
Secondary outcomes:
measure: Change in the Patient Health Questionnaire-9 (PHQ-9)
timeFrame: Baseline, 4 weeks (after treatment period)
Other outcomes:
Locations:
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
Study officials:
affiliation: University of Michigan
name: Leslie Swanson, PhD
role: PRINCIPAL_INVESTIGATOR
References: