From Prevention to Treatment: How Biological Rhythms Can Maintain Perinatal Mental Health

Anxiety State Clinical Trial

Official title:

Innovations in Biological Rhythms in the Context of Mental Health: Effectiveness of New Technologies and Exposure to Different Lighting Patterns in Women During the Postpartum Period

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT06246214
• Other study ID #: 2022-0584
• Status: Active, not recruiting
• Phase: Phase 2/Phase 3
• Start date: January 4, 2024
• Est. completion date: May 2027

Study information

• Verified date: January 2024
• Source: Hospital de Clinicas de Porto Alegre
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Depression and anxiety are significant public health issues during pregnancy and the postnatal period, particularly affecting those in developing countries. Disruptions in biological rhythms, sleep problems, and low exposure to daylight are associated with a higher risk of these mental health issues. The perinatal period poses unique challenges to the temporal program, with evidence indicating that sleep disturbances significantly increase the risk of postnatal depression. A Randomised Clinical Trial (RCT) is being conducted to assess the effectiveness of Blue Light Therapy (BlueLT) in treating depressive and anxiety symptoms during the postpartum. The RCT will also investigate the alignment of rest-activity and internal body time as mediating factors. This study will focus on various chronobiological factors, including rest-activity rhythms, light exposure levels, temperature rhythms, sleep duration and phase, social jetlag, and BodyTime (assessed through a single blood sample). The goal is to recruit 50 women with postpartum depression, with 25 in the BlueLT intervention group and 25 in the ControlLT placebo group, alongside 100 healthy controls. The BlueLT device uses a short-wavelength LED lamp mainly composed by a wavelength peak on blue spectrum, while the ControlLT device has a dim long-wavelength LED. A Healthy Control group will also be included to account for changes unrelated to depression diagnosis or placebo/treatment effects. Exclusion criteria involve a history of major depressive or anxiety disorder, current psychotic disorder, night shift work, active suicidal thoughts, unstable medical conditions interfering with data collection, and newborns with severe health conditions. The study aims to evaluate the impact of BlueLT on postpartum depression and understand the role of chronobiological factors in the health/disease process.

Description:

Depression and anxiety during both pregnancy and postnatal periods are major public health problems, with those living in developing countries being most vulnerable. Alterations in biological rhythms, sleep disturbances, and low daylight exposure have been linked with higher risk for these problems. When considering conditions that are known to produce misalignment, the perinatal period could be seen as a standalone model in which there are distinct challenges to the temporal program. Prior evidence suggests that both sleep onset latency and sleep deficits increases risk for symptoms of postnatal depression. In fact, sleep disturbances appear among the most common risk factors for postnatal depression and are linked to a four-fold increased risk for depression. Emerging evidence indicates that changes in factors related to circadian health, such as patterns of sleep, activity, and light exposure, affect mood during the peripartum period. Thus, chronobiological interventions may be promising strategies, from prevention to treatment. Thus, the Randomised Clinical Trial (RCT) aims to evaluate the effectiveness of Blue Light Therapy (BlueLT) in women with postpartum depression, and examine the alignment of rest-activity and internal body time as mediating variables. During the RCT, we will assess chronobiological factors and their implications on the health/disease process. The chronobiological factors that will be studied are rest-activity rhythms, levels of light exposure, temperature rhythms, sleep duration and phase, social jetlag, and BodyTime (a simple assay from a single blood sample taken at any time of the day). We will recruit women until we ensure the sample size for our nested BlueLT RCT: 50 women with postpartum depression, with 25 in the intervention group (BlueLT) and 25 in the placebo group (ControlLT), along with 100 healthy controls. The BlueLT device is equipped with a narrow band short wavelength Light Emitting Diode (LED) - wavelength peak(λp) of ~470 nm (blue). The ControlLT (placebo) device is equipped with a dim long-wavelength enriched LED. Because pregnancy and postpartum are periods at which changes in phase relationships may happen as an adaptation and not necessarily be disease-promoting will also selected Healthy Control group from the cohort. This group will be the control for changes unrelated to the diagnosis of depression or placebo/treatment effects that may be present. The exclusion criterias are: history of major depressive or anxiety disorder, current psychotic disorder, night shift worker, active suicidal ideation or psychotic symptoms, unstable general medical conditions that interfere with actigraphy acquisition, and newborns with severe health conditions.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 150
• Est. completion date: May 2027
• Est. primary completion date: May 2027
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 4-6 weeks postpartum;
• Postnatal depression confirmed through Edinburgh Postnatal Depression Scale (EPDS) > 10;
• Mini-International Neuropsychiatric Interview (M.I.N.I.) positive for current depressive episode.

Exclusion Criteria:

• Active suicidal ideation;
• Psychotic symptoms;
• Unstable general medical conditions that interfere with the acquisition of actigraphy;
• Newborn with severe health conditions (hospitalization, care in the neonatal ICU).

Related Conditions & MeSH terms

• Anxiety State
• Depression, Postpartum

Intervention

Device:
• Blue Light Therapy
The BlueLT device is equipped with a narrow band short wavelength Light Emitting Diode (LED) - wavelength peak(?p) of ~470 nm (blue).
• ControlLT
The ControlLT (placebo) device is equipped with a dim long-wavelength enriched LED.

Locations

Country	Name	City	State
Brazil	Hospital de Clínicas de Porto Alegre	Porto Alegre	Rio Grande Do Sul

Sponsors (2)

Lead Sponsor	Collaborator
Hospital de Clinicas de Porto Alegre	Federal University of Rio Grande do Sul

Country where clinical trial is conducted

Brazil, 

References & Publications (18)

Allebrandt KV, Teder-Laving M, Cusumano P, Frishman G, Levandovski R, Ruepp A, Hidalgo MPL, Costa R, Metspalu A, Roenneberg T, De Pitta C. Identifying pathways modulating sleep duration: from genomics to transcriptomics. Sci Rep. 2017 Jul 4;7(1):4555. doi: 10.1038/s41598-017-04027-7. — View Citation

Alves Braga de Oliveira M, de Mendonca Filho EJ, Carissimi A, Lima Dos Santos Garay L, Scop M, Ruschel Bandeira D, Gutierrez Carvalho F, Mathur S, Epifano K, Adan A, Frey BN, Hidalgo MP. The Revised Mood Rhythm Instrument: A Large Multicultural Psychometric Study. J Clin Med. 2021 Jan 20;10(3):388. doi: 10.3390/jcm10030388. — View Citation

Comiran Tonon A, Pilz LK, Amando GR, Constantino DB, Boff Borges R, Caye A, Rohrsetzer F, Souza L, Fisher HL, Kohrt BA, Mondelli V, Kieling C, Idiart M, Diez-Noguera A, Hidalgo MP. Handling missing data in rest-activity time series measured by actimetry. Chronobiol Int. 2022 Jul;39(7):964-975. doi: 10.1080/07420528.2022.2051714. Epub 2022 Mar 30. — View Citation

Constantino DB, Xavier NB, Levandovski R, Roenneberg T, Hidalgo MP, Pilz LK. Relationship Between Circadian Strain, Light Exposure, and Body Mass Index in Rural and Urban Quilombola Communities. Front Physiol. 2022 Jan 26;12:773969. doi: 10.3389/fphys.2021.773969. eCollection 2021. — View Citation

Hidalgo MP, Caumo W, Posser M, Coccaro SB, Camozzato AL, Chaves ML. Relationship between depressive mood and chronotype in healthy subjects. Psychiatry Clin Neurosci. 2009 Jun;63(3):283-90. doi: 10.1111/j.1440-1819.2009.01965.x. — View Citation

Kramer A, Lange T, Spies C, Finger AM, Berg D, Oster H. Foundations of circadian medicine. PLoS Biol. 2022 Mar 24;20(3):e3001567. doi: 10.1371/journal.pbio.3001567. eCollection 2022 Mar. — View Citation

Krawczak EM, Minuzzi L, Simpson W, Hidalgo MP, Frey BN. Sleep, daily activity rhythms and postpartum mood: A longitudinal study across the perinatal period. Chronobiol Int. 2016;33(7):791-801. doi: 10.3109/07420528.2016.1167077. Epub 2016 Apr 20. — View Citation

Levandovski R, Dantas G, Fernandes LC, Caumo W, Torres I, Roenneberg T, Hidalgo MP, Allebrandt KV. Depression scores associate with chronotype and social jetlag in a rural population. Chronobiol Int. 2011 Nov;28(9):771-8. doi: 10.3109/07420528.2011.602445. Epub 2011 Sep 6. — View Citation

Pilz LK, Carissimi A, Francisco AP, Oliveira MAB, Slyepchenko A, Epifano K, Garay LLS, Fabris RC, Scop M, Streiner DL, Hidalgo MP, Frey BN. Prospective Assessment of Daily Patterns of Mood-Related Symptoms. Front Psychiatry. 2018 Aug 21;9:370. doi: 10.3389/fpsyt.2018.00370. eCollection 2018. — View Citation

Pilz LK, Carissimi A, Oliveira MAB, Francisco AP, Fabris RC, Medeiros MS, Scop M, Frey BN, Adan A, Hidalgo MP. Rhythmicity of Mood Symptoms in Individuals at Risk for Psychiatric Disorders. Sci Rep. 2018 Jul 30;8(1):11402. doi: 10.1038/s41598-018-29348-z. — View Citation

Pilz LK, de Oliveira MAB, Steibel EG, Policarpo LM, Carissimi A, Carvalho FG, Constantino DB, Tonon AC, Xavier NB, da Rosa Righi R, Hidalgo MP. Development and testing of methods for detecting off-wrist in actimetry recordings. Sleep. 2022 Aug 11;45(8):zsac118. doi: 10.1093/sleep/zsac118. Erratum In: Sleep. 2023 Jul 11;46(7): — View Citation

Pilz LK, Keller LK, Lenssen D, Roenneberg T. Time to rethink sleep quality: PSQI scores reflect sleep quality on workdays. Sleep. 2018 May 1;41(5). doi: 10.1093/sleep/zsy029. — View Citation

Pilz LK, Xavier NB, Levandovski R, Oliveira MAB, Tonon AC, Constantino DB, Machado V, Roenneberg T, Hidalgo MP. Circadian Strain, Light Exposure, and Depressive Symptoms in Rural Communities of Southern Brazil. Front Netw Physiol. 2022 Jan 26;1:779136. doi: 10.3389/fnetp.2021.779136. eCollection 2021. — View Citation

Roenneberg T, Foster RG, Klerman EB. The circadian system, sleep, and the health/disease balance: a conceptual review. J Sleep Res. 2022 Aug;31(4):e13621. doi: 10.1111/jsr.13621. Epub 2022 Jun 7. — View Citation

Slyepchenko A, Minuzzi L, Reilly JP, Frey BN. Longitudinal Changes in Sleep, Biological Rhythms, and Light Exposure From Late Pregnancy to Postpartum and Their Impact on Peripartum Mood and Anxiety. J Clin Psychiatry. 2022 Jan 18;83(2):21m13991. doi: 10.4088/JCP.21m13991. — View Citation

Tonon AC, Constantino DB, Amando GR, Abreu AC, Francisco AP, de Oliveira MAB, Pilz LK, Xavier NB, Rohrsetzer F, Souza L, Piccin J, Caye A, Petresco S, Manfro PH, Pereira R, Martini T, Kohrt BA, Fisher HL, Mondelli V, Kieling C, Hidalgo MPL. Sleep disturbances, circadian activity, and nocturnal light exposure characterize high risk for and current depression in adolescence. Sleep. 2022 Jul 11;45(7):zsac104. doi: 10.1093/sleep/zsac104. — View Citation

Wittenbrink N, Ananthasubramaniam B, Munch M, Koller B, Maier B, Weschke C, Bes F, de Zeeuw J, Nowozin C, Wahnschaffe A, Wisniewski S, Zaleska M, Bartok O, Ashwal-Fluss R, Lammert H, Herzel H, Hummel M, Kadener S, Kunz D, Kramer A. High-accuracy determination of internal circadian time from a single blood sample. J Clin Invest. 2018 Aug 31;128(9):3826-3839. doi: 10.1172/JCI120874. Epub 2018 Aug 6. — View Citation

Xavier NB, Abreu ACVO, Amando GR, Steibel EG, Pilz LK, Freitas JJ, da Silveira Cruz-Machado S, Markus RP, Frey BN, Hidalgo MP. Chronobiological parameters as predictors of early treatment response in major depression. J Affect Disord. 2023 Feb 15;323:679-688. doi: 10.1016/j.jad.2022.12.002. Epub 2022 Dec 5. — View Citation

* Note: There are 18 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Depressive symptoms	The EDPS was developed to identify women who may have postpartum depression. This scale consists of 10 short statements. The participant checks off one of four possible answers that is closest to how she has felt during the past week. Responses are scored 0, 1, 2 and 3 based on the seriousness of the symptom. Items 3, 5 to 10 are reverse scored (i.e., 3, 2, 1, and 0). The total score is found by adding together the scores for each of the 10 items. A total score higher than 10 indicate the presence of depressive symptoms. A reduction in depressive symptoms clinically significant (outcome measure) will consist in a minimum difference of 4 points on the EPDS.	From enrollment to the end of treatment at 4 weeks
Primary	Anxiety symptoms	The General Anxiety Disorder 7-item scale (GAD-7) is one of the tools used to screen for anxiety or to measure its severity. Total score is calculated by assigning scores of 0, 1, 2, and 3 to the response categories, respectively, of "not at all," "several days," "more than half the days," and "nearly every day." Ranging from 0 to 21, the following threshold were previously proposed: 0-4 (minimal anxiety); 5-9 (mild anxiety); 10-14 (moderate anxiety); 15-21 (severe anxiety). A reduction in anxiety symptoms clinically significant (outcome measure) will consist in a minimum difference of 4 points on the GAD-7.	From enrollment to the end of treatment at 4 weeks