DRACULA1 Partum Depression: an Integrated Molecular-pharmaco-imaging Study")

November 8, 2023 updated by: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

("The Role of the Glutamatergic Neurotransmission in Post- Partum Depression: an Integrated Molecular-pharmaco-imaging Study")

Post-partum depression (PPD) is a prevalent subtype of major depressive disorder that causes a significant distress to the woman and substantial impact on the whole family. Many studies implicate the glutamatergic system in pathological processes relevant to PPD disorders. There is evidence that cell adhesion molecules (CAMs) play a key role in how glutamatergic circuits wire up during development and how glutamatergic synapses, once formed, operate. However, it is unclear how dysregulation in diverse CAMs alter glutamatergic circuitries responsible for emotional and social behavior.

Here, the investigators propose to evaluate the molecular and neurobiological underpinnings of PPD focusing on CAMs at glutamatergic synapses by using an integrated approach from mouse models to human patients. Moreover, the investigators will also perform a pilot study to investigate the impact of selective antidepressants, known to be linked to CAMs, in both human and mice.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Patients will be recruited by the physician in charge of the study or collaborators of the S.C. Neonatology and Neonatal Intensive Care Unit of the IRCCS Ca' Granda Ospedale Maggiore Policlinico Foundation upon referral from the S.C. Psychiatry of the same institution. In the study, exposure to citalopram treatment will be 12 weeks with follow-up every 4 weeks. At each participant, at the time of enrollment, will be assigned a unique code so that only the local investigators can trace the subject's identity. As part of a scheduled visit to assess the clinical diagnosis, the PPD patient will be offered to participate in the study, after the appropriate signing of informed consent, the verification of absence of criteria for exclusion and existence of the study inclusion criteria. If these criteria are met, some demographic and clinical medical history of the women with PPD will be collected, as already provided by clinical practice for the management of the disease. Patients will undergo MRI scanning at baseline at the S.C. Neuroradiology of the Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico and will begin the pharmacological treatment with citalopram. It is emphasized that the administration of citalopram therapy for the treatment of depressive symptomatology will be proposed and carried out in the patient due to clinical needs, based on the judgment of the competent physician and as would already be the case in practice, thus completely independent of participation or non-participation in the present study. Neuroimaging data will be obtained with a Philips 3T magnetic resonance imaging MRI machine. For each patient enrolled in the study, a structural T1 sequence (3D MPRAGE) is acquired.

T1-weighted MRI images will be used to study the differences brain morphology, including the volumes of gray matter (GM) and white matter (WM) and voxel-based morphometry. In a comparison parallel between regions of interest (ROIs), regional volumes will be estimated using the automated anatomical labeling atlas (AAL) as a reference, with emphasis on the dorsolateral PFC (DL)/ventrolateral (VL), cingulate cortex, amygdala and hippocampus. Further regional analysis will allow estimation, in addition to cortical volumes and subcortical volumes, cortical thickness, cortical surface area, and the cortical gyrification of the Desikan-Killiany atlas regions. During treatment with citalopram, patients will be visited, as per standard clinical practice, every 4 weeks. At each of these follow-up visits will be administered to patients by medical specialists the Brief Psychiatric Rating Scale (BPRS) and the Hamilton Depression Rating Scale (HAM- D) to study symptomatology depression. Patients will be, instead, self-administered in Italian language the Maternal Postnatal Attachment Scale (MPAS) and the Parental Stress Index (PSI) to investigate mother-child attachment and parental stress. The time scheduled for completion of both scales will be about 40 minutes. At 12 weeks, as per practice, the MRI scan will be repeated at the S.C. Neuroradiology Department of the Foundation. The following variables will be collected as part of this study: socio-demographic variables (age, schooling, socio-economic);

  • clinical/anamnestic variables (age of onset, duration of untreated treated, drug therapy, comorbidities, familiarity, substance abuse/dependence);
  • BPRS and HAM-D scales scores for symptomatology assessment (T0, T1, T2, T3);
  • MPAS and PSI scales scores for the assessment of mothers child attachment. (T0, T1, T2, T3);
  • MRI scan data (T0, T3): the images will be used to study brain morphological differences, including GM and WM volumes, and voxel-based morphometry. In a parallel comparison between regions of interest (ROI), regional volumes will be estimated using as a reference the automated anatomical labeling atlas (AAL), with particular attention to the dorsolateral (DL)/ventrolateral (VL) PFC, cingulate cortex, amygdala and hippocampus. A further regional analysis will make it possible to estimate, in addition to cortical and subcortical volumes, the thickness cortical, cortical surface area and cortical gyrification of the Desikan-Killiany atlas regions.

Study Type

Observational

Enrollment (Estimated)

15

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Italy
    • MI
      • Milan, MI, Italy, 20100
        • Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Women, aged 18 years to 40 years of age or older, with PPD who will be enrolled by the S.C. Neonatology and Neonatal Intensive Care Unit of the IRCCS Ca' Granda Ospedale Maggiore Policlinico Foundation upon referral from the S.C. Psychiatry of the same institution.

Description

Inclusion Criteria:

  • Age between 18 and 40 years;
  • female gender;
  • PPD diagnosed by DSM-5 structured clinical interview support (SCID-5) by trained medical personnel;
  • comorbidity with metabolic syndrome, which can lead to brain damage and cognitive flaws;
  • need to start citalopram therapy for clinical needs (and therefore independent of study participation) or already on therapy for no more than two weeks;
  • moderate to severe depression according to the 17-item HAM-D (score 14-24);
  • absence of disabling medical and/or neurological conditions, including heart attacks, brain injuries, neurodegenerative diseases, head trauma with loss of consciousness for more than 30 minutes;
  • Absence of concomitant psychiatric therapies (antidepressants, antipsychotics of the first and second generation and mood stabilizers);
  • absence of contraindications for MRI scanning;
  • patients who have signed informed consent.

Exclusion Criteria:

  • age below 18 years or above 40 years;
  • diagnosis different from PPD based on SCID-5;
  • absence of metabolic syndrome;
  • low depression according to the 17-item HAM-D (score less than 14);
  • presence of disabling medical and/or neurological conditions, including heart attacks, brain injuries, neurodegenerative diseases, head trauma with loss of consciousness for more than 30 minutes;
  • presence of concomitant drug therapies (antidepressants, first- and second-generation antipsychotics and mood stabilizers);
  • presence of contraindications for MRI scanning;
  • presence of contraindications for citalopram;
  • patients who have not signed informed consent.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Women with Post-Partum Depression
15 women with PPD referred to the S.C. Psychiatry of IRCCS Ca' Granda Ospedale Maggiore Policlinico Foundation and referred to the S.C. Neonatology and Neonatal Intensive Care Unit of the same institution for enrollment.
Drug: Citalopram
Patients will be administered citalopram, regardless of inclusion or non-inclusion in this study, on medical indication, as per normal clinical practice for disease management and according to the Summary of Product Characteristics (SPC). Patients will have two MRI scans done (at baseline and at 12 weeks after the start of therapy) to assess: brain volumetry, tissue amount of gray matter - GM - and white matter - WM

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Evaluate the citalopram effect on white matter morphology
Time Frame: 12 weeks
Any statistically significant changes in brain volumetry and in the tissue amount of white matter (WM) will be evaluated after 12 weeks of treatment with citalopram.
12 weeks
Evaluate the citalopram effect on gray matter morphology
Time Frame: 12 weeks
Any statistically significant changes in brain volumetry and in the tissue amount of gray matter (GM) will be evaluated after 12 weeks of treatment with citalopram.
12 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To evaluate the efficacy of citalopram on the clinical symptomatology of the PPD patients through the use of clinical scales
Time Frame: 12 weeks
Variation of the score of HAM-D for measuring patients' symptomatology after 12 weeks after the start of treatment. Patients will be considered responsive if they have at least a 30% reduction from baseline HAM-D baseline after 12 weeks of treatment with citalopram.
12 weeks

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Assess the tolerability profile of the drug in the same patients
Time Frame: 12 weeks
Evaluation of the serious and nonserious adverse events number judged by the medical staff to be related to the drug under study.
12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

January 1, 2024

Primary Completion (Estimated)

December 1, 2025

Study Completion (Estimated)

April 30, 2026

Study Registration Dates

First Submitted

April 13, 2023

First Submitted That Met QC Criteria

November 8, 2023

First Posted (Actual)

November 14, 2023

Study Record Updates

Last Update Posted (Actual)

November 14, 2023

Last Update Submitted That Met QC Criteria

November 8, 2023

Last Verified

March 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DRACULA 1

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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