Relationship Between Major Depression and Periodontal Diseases

Major Depressive Disorder Clinical Trial

— LeakyBraInCS  

Official title:

Relationship Between Major Depression and Periodontal Diseases: Analytical Cross-sectional Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05950009
• Other study ID #: URI 106-260623
• Status: Recruiting
• Start date: February 20, 2024
• Est. completion date: March 2026

Study information

• Verified date: May 2024
• Source: Universidad Complutense de Madrid
• Contact: Elena Figuero Ruiz, Prof.
• Phone: 0034913942186
• Email: elfiguer[@]ucm.es
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Background: There are epidemiological and preclinical studies in vivo that support the biological plausibility of the association between periodontal diseases and major depression (DM), through the hypothesis of a "leaky mouth" by periodontitis as a source of neuroinflammation. Therefore, this association should be studied in depth in carefully designed cross-sectional studies in humans to specifically assess this relationship.

Objectives: Primary: determine if periodontitis can be associated with the development of DM. Secondary: (1) to estimate the prevalence of periodontal diseases (gingivitis and periodontitis) in patients with and without DM; (2) to determine whether oral, periodontal, and fecal (bacterial, viral, and fungal) metagenomic microbiomes, inflammatory mediators, and intestinal barrier integrity are associated with periodontal and mental health variables.

Material and method:

A cross-sectional analytical study with two groups is designed:

• Control group (without DM): subjects without known mental health pathologies will be included, who present a PHQ-9 index of 5 or less. They will be recruited from the control group of a population-based study PsychoBioma TRIAD (C.P. PSQ-19-2 - C.I. 19/474-E). They will be matched by age, gender, and socioeconomic status.

• Group of cases (MD patients): subjects with moderate DM will be selected, characterized by HPQ9 index values of 9 or higher. They will be selected among those patients who attend the Mental Health consultations associated with the San Carlos Clinical Hospital.

The study will consist of three visits:

• Visit in Mental Health Consultations: in this visit the subject will be evaluated to determine if he meets the eligibility criteria. You will be informed of the purpose of the study and you will be invited to participate and sign the informed consent. After that, a structured clinical interview for the DSM-IV (SCID) will be conducted and the subject will fill in a series of specific scales on a study-specific electronic device [Beck Depression Inventory (BDI); UCLA Loneliness Scale, Center for Epidemiologic Studies Depression scale [CES-D]; Childhood Trauma Questionnaire short form (CTQ-SF); The World Health Organization Quality of Life questionnaire (WHOQOL); Hamilton scale (HAM-D17); Global Assessment of Functioning (GAF) Scale].

• Dental School Visit: Subject will receive a comprehensive periodontal examination. A subgingival microbiological sample, a saliva sample and a blood sample will also be taken. The patient will be given a specific vial to collect stool samples.

• At the participant's home: the stool samples will be deposited by the participants at home in the specific collection vial.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 122
• Est. completion date: March 2026
• Est. primary completion date: January 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age greater or equal to 18 years.

• For the case group (MD patients), subjects with moderate or severe major depression, without severe suicide ideation, as characterized by the Patient Health Questionnaire (PHQ)-9 index (values of 9 or greater) and by the Structured Clinical Interview for DSM-5 - (SCID) will be selected.

• For the control group, subjects without mental health pathologies identified by SCID, who present an PHQ-9 index of 5 or below will be included as controls.

Exclusion Criteria:

• Pregnant or breastfeeding women.

• Diabetes mellitus.

• Chronic conditions: HIV infection, chronic intake of NSAIDs.

• Comorbidity with other mental disorders: eating disorders, borderline personality disorders, bipolar disorders, schizophrenia and related disorders, and/or any mental serious disease other than major depression.

• Severe suicide ideation.

• Patients who had received periodontal treatment for periodontitis in the last year.

• Presence of necrotizing periodontal diseases.

• Presence of less than three teeth per quadrant.

• Antibiotic use in the last 6 months prior to the study.

Related Conditions & MeSH terms

• Depressive Disorder
• Depressive Disorder, Major
• Major Depressive Disorder
• Periodontal Diseases
• Periodontitis

Intervention

Other:
• No intervention (observational studies)
No intervention (observational studies)

Locations

Country	Name	City	State
Spain	Faculty of Dentistry, University Complutense of Madrid (UCM)	Madrid
Spain	Instituto de Psiquiatría y Salud Mental, Hospital Clínico San Carlos	Madrid

Sponsors (2)

Lead Sponsor	Collaborator
Universidad Complutense de Madrid	Ministerio de Economía y Competitividad, Spain

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Periodontitis (presence/absence)	With the clinical and radiological information, the periodontal diagnosis of the patients will be established according to the 2018 classification of periodontal and peri-implant diseases), which involves determining the stage (I to IV), the extent of the stage (localized, generalized or incisor-molar pattern) and the grade (A, B or C).	Baseline
Secondary	Childhood Trauma Questionnaire short form (CTQ-SF)	Range: 25 to 125. A higher score means more (and worst) traumatic experience.	Baseline
Secondary	UCLA Loneliness Scale (Spanish version)	Range: 20 to 80. Higher scores indicatehigher levels of loneliness	Baseline
Secondary	The World Health Organization Quality of Life questionnaire (WHOQOL)	Range: 0 to100. A higher score means better quality of life.	Baseline
Secondary	Beck Depression Inventory (BDI)	Range: 0 to 63. A higher score means more severe-depressive symptomatology	Baseline
Secondary	Centre for Epidemiologic Studies Depression scale [CES-D]	Range: 0 to 60. Higher scores indicate the presence of more severe symptomatology	Baseline
Secondary	Hamilton scale (HAM-D17)	Range: 0 to 52. The higher the score, the more severe the depressive symptoms	Baseline
Secondary	Global Assessment of Functioning (GAF) Scale.	Range: 1 to 100. A higher score means better functioning. A score of 0 means Inadequate information.	Baseline
Secondary	Subgingival microbiota	Bacterial DNA extraction will be performed using a commercial kit (Molzym Gmbh& Co.KG; Bremen, Germany) specific for bacterial DNA extraction. DNA samples will be frozen at -80°C and preserved until further analysis by quantitative polymerase chain reaction (q-PCR) (Marin et al., 2019) and 16S rRNA sequencing, using the Illumina MiSeq platform. The analysis of sequences obtained for the microbiome will include: a) quality control and trimming: PCR primers, chimeric sequences, and short and low-quality reads will be discarded; b) mapping: annotation at different taxonomic levels; c) rarefaction curves; d) quantification: counts and percentages of the presence of specific bacteria in each sample at different taxonomic levels; e) calculation of the biodiversity index and f) comparison between samples. The analysis by q-PCR will include the detection and quantification of the most prevalent or abundant species.	Baseline
Secondary	Plasma levels of inflammatory mediators	plasma levels of inflammatory mediators IL-1ß, TNF-a, IL-6, prostaglandin E2 and CPRhs	Baseline
Secondary	Saliva microbiota	microbial DNA will be used for library preparation and metagenomic shotgun sequencing using the Illumina HiSeq 2500 System. Shotgun metagenomic sequencing can identify bacteria, fungi, and viruses, with a resolution that allows species-level identification. Sequences are compared to phylogenetic and functional databases to obtain taxonomic and functional profiles	Baseline
Secondary	Gut microbiota (Stool samples)	microbial DNA will be used for library preparation and metagenomic shotgun sequencing using the Illumina HiSeq 2500 System. Shotgun metagenomic sequencing can identify bacteria, fungi, and viruses, with a resolution that allows species-level identification. Sequences are compared to phylogenetic and functional databases to obtain taxonomic and functional profiles	Baseline