Personalized Integrated Chronotherapy for Perinatal Depression

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.

Study Overview

• Status: Recruiting
• Conditions: Depression; Postpartum Depression; Sleep Disturbance; Pregnancy Related; Circadian Dysregulation; Prenatal Disorder
• Intervention / Treatment: Behavioral: Personalized Integrated Chronotherapy

Detailed Description

The purpose of this research study is to collect data on whether adding light therapy and a prescribed sleep schedule to usual treatment for depression can reduce depression and anxiety symptoms during pregnancy and the postpartum. The study is enrolling pregnant woman between the ages of 18 and 40 who have been diagnosed with depression and (possibly) anxiety.

This study takes place from the 3rd trimester of pregnancy to 18 weeks postpartum. Women who take part in this study will be randomly assigned ("randomized") into one of the study treatment groups (1) the "usual care" group (UC); or (2) the group that receives bright light therapy and a prescribed sleep schedule, also called the "Personalized Integrated Chronotherapy" group (PIC). The usual care group will receive medications and/or talk therapy as decided by the woman and her doctor. Women in the integrated chronotherapy group will receive usual care (as above) and will also receive a bright light box to sit with every morning for up to 60 minutes as prescribed by the study doctor. Light will be delivered with a portable, broad-spectrum light box. Both groups will have their sleep and light levels monitored during 3rd trimester of pregnancy (weeks 28-40) and weeks 2-6 and 18 after the baby is born (postpartum weeks 2-6 and 18) Sleep monitoring takes place in the home using a small wrist activity monitor called an "actigraph." Participants will also be asked to provide three saliva sample sets over the course of the study to measure melatonin levels.

In addition to the "Personalized Integrated Chronotherapy" study treatment that will supplement the clinical care as described above, participants will be asked to come in for research study visits.

• Study Type: Interventional
• Enrollment (Estimated): 220
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Katherine M Sharkey, MD, PhD; Phone Number: 401-793-3497; Email: katherine_sharkey@brown.edu

Study Locations

• United States
  • New York
    • Glen Oaks, New York, United States, 11004
      • Recruiting
      • Feinstein Institute for Medical Research
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Recruiting
      • University of North Carolina
      • Contact: Samantha Meltzer-Brody, MD,MPH
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Recruiting
      • Rhode Island Hospital
      • Contact: Katherine M Sharkey, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

- 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)

Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Usual Care; 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; 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.; Other Names: Bright Light Therapy; Chronotherapy; Triple Chronotherapy
Experimental: Personalize Integrated Chronotherapy; 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; 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.; Other Names: Bright Light Therapy; Chronotherapy; Triple Chronotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Depressive Symptoms	Score on the Hamilton Depression Rating Scale (range=0-54, higher scores indicate more depressive symptoms)	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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Circadian Phase	Time of salivary dim light melatonin onset (DLMO)	change from baseline at 36 weeks pregnancy
Change in Circadian Phase	Time of salivary dim light melatonin onset (DLMO)	change from baseline at 6 weeks postpartum
Change in Sleep Timing	time of sleep onset and sleep offset measured with wrist actigraphy	change from baseline at 33 weeks of pregnancy
Change in Sleep Timing	time of sleep onset and sleep offset measured with wrist actigraphy	change from baseline at 36 weeks of pregnancy
Change in Sleep Timing	time of sleep onset and sleep offset measured with wrist actigraphy	change from baseline at 2 weeks postpartum
Change in Sleep Timing	time of sleep onset and sleep offset measured with wrist actigraphy	change from baseline at 6 weeks postpartum
Change in Sleep Timing	time of sleep onset and sleep offset measured with wrist actigraphy	change from baseline at 18 weeks postpartum
Infant sleep behavior	infant sleep-wake patterns will be measured with one week of ankle actigraphy	18 weeks postpartum
Melatonin levels and timing of onset in breastmilk	We will examine associations between salivary melatonin levels and melatonin levels in breast milk	18 weeks postpartum

Collaborators and Investigators

• Sponsor: Rhode Island Hospital
• Collaborators: Northwell Health; University of North Carolina, Chapel Hill
• Investigators: Principal Investigator: Kristina M Deligiannidis, MD, Northwell Health; Principal Investigator: Samantha Meltzer-Brody, MD, University of North Carolina, Chapel Hill

Study record dates

Study Major Dates

• Study Start (Actual): November 2, 2020
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): June 1, 2024

Study Registration Dates

• First Submitted: April 6, 2020
• First Submitted That Met QC Criteria: April 24, 2020
• First Posted (Actual): April 28, 2020

Study Record Updates

• Last Update Posted (Actual): July 5, 2023
• Last Update Submitted That Met QC Criteria: June 30, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Nervous System Diseases; Mood Disorders; Sleep Wake Disorders; Pregnancy Complications; Puerperal Disorders; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Depression; Depressive Disorder; Dyssomnias; Parasomnias; Depression, Postpartum; Chronobiology Disorders
• Other Study ID Numbers: 18-0913

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Per NIMH guidelines
• IPD Sharing Time Frame: when study is concluded and data are prepared
• IPD Sharing Access Criteria: with approval from PI and regulatory bodies
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No