Correcting Circadian Rhythms to Breakthrough in Bipolar Disorder

Leslie Swanson

Status and phase: Enrolling; Phase 2

Conditions: Bipolar Disorder; Delayed Sleep-Wake Phase Disorder

Treatments: Drug: Melatonin; Behavioral: Behavioral sleep intervention; Other: Placebo; Behavioral: Behavioral sleep control

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT06226025

1R21MH132901-01A1 (U.S. NIH Grant/Contract)

HUM00235778

Details and patient eligibility

About

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.

Full 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.

Enrollment: 50 estimated patients

Sex: All

Ages: 18 to 60 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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50 participants in 2 patient groups, including a placebo group

Melatonin

Experimental group

Description:

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.

Treatment:

Behavioral: Behavioral sleep intervention

Drug: Melatonin

Placebo

Placebo Comparator group

Description:

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.

Treatment:

Behavioral: Behavioral sleep control

Other: Placebo