Personalized Integrated Chronotherapy for Perinatal Depression

NCT04364646 | Completed Results DMC

• 1 other identifier: 18-0913
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 3

Brief Summary

Perinatal depression and anxiety are common, serious, and frequently overlapping disorders that increase morbidity and mortality in new mothers (including suicide) and result in poor infant/child outcomes. Current therapies often fail to produce recovery or are poorly tolerated, and many pregnant women seek non-pharmacologic therapy or forgo treatment when non-pharmacologic options are not available. Expectant and new mothers who experience circadian rhythm dysregulation are at increased risk for perinatal depression. This Confirmatory Efficacy Clinical Trial of Non-Pharmacological Interventions for Mental Disorders R01 seeks to test whether a Personalized Integrated Chronotherapy (PIC) intervention can improve treatment outcomes for pregnant patients seeking outpatient treatment for depression, with or without anxiety. PIC is a multicomponent treatment consisting of bright light therapy, sleep phase advance, and sleep stabilization/restriction that targets the Research Domain Criteria (RDoC) constructs of circadian rhythms and sleep-wake behavior. To increase sample size and diversity and accelerate recruitment, this study will be performed at 4 sites that differ in clinical structure and that have piloted the PIC intervention. The study will enroll expectant mothers diagnosed with major depressive disorder during 3rd trimester of pregnancy. Participants will be randomized to either: (a) usual care (UC, n = 110) or (b) PIC+UC (n = 110). PIC+UC will have pregnancy and postpartum components and will be administered via a personalized approach tailored to optimize the intervention based on each patient's individual circadian and sleep timing. After a baseline assessment, PIC will be prescribed during 5 dedicated clinical visits: three during 3rd trimester of pregnancy and 2 in the postpartum period. UC will consist of medication and/or psychotherapy. UC will be quantified in both groups to evaluate differences between the PIC+UC and UC groups. Mood will be measured in both groups by blinded clinician interview and patient self-report. The safety profile of the PIC intervention will be assessed by evaluation of side effects/adverse events. Importantly, the study will also examine the target mechanisms by which PIC is hypothesized to work and test the mediation effects of the circadian targets on improvement in mood symptoms. Participants will wear wrist actigraphy/light monitors continuously during weeks 28-40 of pregnancy and postpartum weeks 2-6 to assess light exposure and to estimate sleep timing and duration. Circadian phase (measured with salivary dim light melatonin onset) will be measured at baseline during pregnancy (\~30 weeks' gestation), at 36 weeks' gestation, and at postpartum week 6. Exploratory aims will examine associations between infant sleep behavior and maternal circadian rhythms and factors relevant to future dissemination of PIC. If this intervention is effective, perinatal PIC could change clinical practice and have major public health impact due to the high prevalence of perinatal depression and anxiety, the negative effects of mood disorders on mothers and their children, and the need to provide effective, novel, non-pharmacologic therapies for women with perinatal mood disorders.

Conditions

Depression; Postpartum Depression; Prenatal Disorder; Circadian Dysregulation; Pregnancy Related; Sleep Disturbance

Outcome Measures

Primary Outcomes (5)

• Change in Depressive Symptoms

  Change in the Hamilton Depression Rating Scale score (range=0-54, higher scores indicate more depressive symptoms), average baseline score was \~19 in both groups, and remission goal is a score of 7 or a change of \~12.

  change from baseline at 33 weeks of gestation

• Change in Depressive Symptoms

  Score on the Hamilton Depression Rating Scale (range=0-54, higher scores indicate more depressive symptoms)

  change from baseline at 36 weeks of gestation

• Change in Depressive Symptoms

  Score on the Hamilton Depression Rating Scale (range=0-54, higher scores indicate more depressive symptoms)

  change from baseline at 2 weeks postpartum

• Change in Depressive Symptoms

  Score on the Hamilton Depression Rating Scale (range=0-54, higher scores indicate more depressive symptoms)

  change from baseline at 6 weeks postpartum

• Change in Depressive Symptoms

  Score on the Hamilton Depression Rating Scale (range=0-54, higher scores indicate more depressive symptoms)

  change from baseline at 18 weeks postpartum

Secondary Outcomes (9)

• Change in Circadian Phase

  change from baseline at 36 weeks pregnancy

• Change in Circadian Phase

  change from baseline at 6 weeks postpartum

• Change in Sleep Timing

  change from baseline at 33 weeks of pregnancy

• Change in Sleep Timing

  change from baseline at 36 weeks of pregnancy

• Change in Sleep Timing

  change from baseline at 2 weeks postpartum

Study Arms (2)

Usual Care

ACTIVE COMPARATOR

Women in the usual care group receive medications and/or talk therapy. Sleep and light levels are monitored at home with wrist actigraphy during 3rd trimester of pregnancy (weeks 28-40) and weeks 2-6 and18 after the baby is born (postpartum weeks 2-6 and 18).

Behavioral: Personalized Integrated Chronotherapy

Personalize Integrated Chronotherapy

EXPERIMENTAL

Women in the integrated chronotherapy group receive usual care (medications and/or talk therapy, as above) and also receive a bright light box to sit with every morning for up to 60 minutes as prescribed by the study doctor.

Behavioral: Personalized Integrated Chronotherapy

Interventions

Personalized Integrated Chronotherapy BEHAVIORAL

Based on their baseline sleep-wake schedule and real-life constraints (work and other responsibilities), an initial sleep schedule is set that allows 7.5 hours of sleep and provides time for participants to sit in front of the morning bright light.

Also known as: Chronotherapy, Triple Chronotherapy, Bright Light Therapy

Personalize Integrated Chronotherapy; Usual Care

Eligibility Criteria

• Age: 18 Years - 45 Years
• Gender Eligibility Details: people who can become pregnant are eligible, i.e., female sex; any gender identity can be enrolled but must be pregnant
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• \- pregnant women, ages 18-45 years with a HAMD score \>=14 and a current DSM-5 diagnosis of major depressive disorder as determined with the Current Major Depression Module of the Structured Clinical Interview for DSM disorders (SCID-I/P)

You may not qualify if:

• active psychosis or suicidality contraindicating outpatient treatment as determined by the clinical judgement of the research team and as measured with the B/C module of the SCID-I/P and the Columbia-Suicide Severity Rating Scale
• bipolar disorder (because sleep restriction can increase risk of conversion to mania)
• seizure disorder (because sleep restriction can increase seizure risk)
• self report of frequent migraines/headaches precipitated by bright light or sleep deprivation
• preexisting eye/skin disorders contraindicating light therapy
• use of photosensitizing medications
• primary Axis I diagnosis other than MDD (e.g., anorexia nervosa, ADHD)
• high risk pregnancy (e.g., conditions requiring mandatory bed rest or complex medical regimens that will interfere with study participation or conditions where poor infant outcomes are anticipated)
• starting antidepressants in the 4 weeks prior to enrollment
• current employment as night shift worker
• Alcohol Use Disorders Identification Test (AUDIT) score \> 8 and/or Drug Abuse Screening Test (DAST) \> 1 indicating current alcohol or drug use disorders
• women whose infants will not be living in the home or who will have a nighttime caregiver
• Pittsburgh Sleep Quality Inventory (PSQI)190 \< 5 (i.e., those who report no sleep complaints during 3rd trimester of pregnancy and for whom an intervention targeting sleep might not be indicated).
• women who do not speak and read English because PIC research instruments are only available in English at this time. If this RCT shows effectiveness, future work will examine effectiveness in women who speak and read languages other than English.
• Women who experience fetal loss or stillbirth, as well as mothers whose infants are born before 36 weeks' gestation or have NICU stays \> 5 days, will be discontinued from the study but will continue to receive UC.

Sponsors & Collaborators

• Rhode Island Hospital: lead
• Northwell Health: collaborator
• University of North Carolina, Chapel Hill: collaborator

Study Sites (3)

Feinstein Institute For Medical Research

Glen Oaks, New York, 11004, United States

Location

University of North Carolina

Chapel Hill, North Carolina, 27599, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

MeSH Terms

Conditions

Depression; Depression, Postpartum; Chronobiology Disorders; Parasomnias

Interventions

Chronotherapy; Ultraviolet Therapy

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior; Puerperal Disorders; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Depressive Disorder; Mood Disorders; Mental Disorders; Nervous System Diseases; Sleep Wake Disorders

Intervention Hierarchy (Ancestors)

Therapeutics; Phototherapy

Results Point of Contact

• Title: Katherine M. Sharkey, MD, PhD
• Organization: Center for Sleep and Circadian Rhythms, AHWFB

katherine.sharkey@advocatehealth.org

336-716-4657

Study Officials

• Kristina M Deligiannidis, MD

  Northwell Health

  PRINCIPAL INVESTIGATOR

• Samantha Meltzer-Brody, MD

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: outcome assessments are made by a blinded investigator
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 6, 2020
• First Posted: April 28, 2020
• Study Start: November 2, 2020
• Primary Completion: October 22, 2024
• Study Completion: June 30, 2025
• Last Updated: December 9, 2025
• Results First Posted: December 9, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, CSR
• Time Frame: when study is concluded and data are prepared
• Access Criteria: with approval from PI and regulatory bodies

Locations

US (3)