Impact of Periodontal Therapy on Mental Health Parameters

Depression Clinical Trial

— LeakBrainRCT  

Official title:

Impact of Periodontal Therapy on Mental Health Parameters in Patients With Major Depression and Periodontitis: a Pilot Randomized Controlled Clinical Trial.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06036472
• Other study ID #: URI 107-260623
• Status: Recruiting
• Phase: N/A
• Start date: March 14, 2024
• Est. completion date: January 2026

Study information

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

Clinical Trial Summary

Objectives: Primary: To determine the efficacy of periodontal treatment on mental health outcomes in patients with major depression and periodontitis. Secondary: To identify the effect of periodontal treatment on oral, periodontal, and fecal metagenomic microbiomes, and on systemic levels of inflammation (bacterial, viral, and fungal) and their impact on mental health outcomes.

Material and method:

A 6-month pilot randomized controlled clinical trial is designed. The study will be conducted in patients with moderate or severe DM (Patient Health Questionnaire-9 [PHQ-9] index of 9 or higher) and stage III-IV periodontitis who will be assigned to two different interventions:

• Test group: standard periodontal treatment consisting of two sessions of supragingival and subgingival debridement (steps 1 and 2) under local anesthesia.

• Control group: periodontal treatment consisting of two sessions of supragingival debridement (step 1) under local anesthesia.

The study will consist of 6 visits:

• Screening visit (v0)

• Baseline visit (v1):

• In the mental health center: patients will receive a structured clinical interview for the DSM-IV (SCID) and the patient will fill out 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].

• At the UCM School of Dentistry: patients will receive a complete periodontal examination (clinical and radiographic). A subgingival microbiological sample, a saliva sample and a blood sample will also be taken.

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

• Intervention visits (v2-3): Two periodontal treatment sessions (test or control) will be carried out one week apart.

• Re-evaluation visit (v4): Six weeks after treatment, all periodontal clinical variables will be recorded.

• Follow-up visits at 3 and 6 months: after periodontal treatment, all the variables recorded at the baseline visit will be taken

Statistical analysis:

Periodontal treatment (test/control) will be considered as the independent variable and the Hamilton scale (HAM-D17) will be considered the primary response variable. The rest of the variables will be considered as secondary variables. A crude bivariate analysis of comparison of means or proportions will be carried out depending on the nature of the variable. In addition, crude and adjusted regression models will be performed.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: January 2026
• Est. primary completion date: January 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

5.3.1. Inclusion criteria:

• Age greater or equal to 18 years.

• Patients 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.

• Subjects with periodontitis stages III or IV, according to the 2018 Classification on periodontal and peri-implant diseases (Papapanou et al., 2018).

5.3.2. 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.

• Smokers of 10 or more cigarettes per day.

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

• Presence of necrotizing periodontal diseases.

• Presence of less than 3 teeth per quadrant.

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

Related Conditions & MeSH terms

• Depression
• Periodontitis

Intervention

Procedure:
• Standard periodontal therapy (steps 1 & 2)
participant will receive standard periodontal treatment consisting of two sessions of supra- and subgingival debridement (steps 1 and 2) under local anesthesia following current guidelines for periodontal therapy in patients with periodontitis (Herrera et al., 2022; Sanz et al., 2020). The use of chlorhexidine (0.12%) and cetylpyridinium chloride (0.05%) mouthwash will be prescribed twice a day for 15 days (Perio-Aid®, Dentaid, Barcelona, Spain). If needed, hopeless teeth might be extracted during this step.
• supragingival debridement with anesthesia (step 1)
periodontal treatment consisting of two sessions of supragingival debridement with anesthesia (step 1) and administration of a placebo mouthwash (FluorAid®, Dentaid, Barcelona, Spain), twice a day for 15 days.

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
Other	Plaque index	presence/absence	Baseline
Other	Plaque index	presence/absence	3 months
Other	Plaque index	presence/absence	6 months
Other	Bleeding on probing	Assessed dichotomously within 15 seconds after probing	Baseline
Other	Bleeding on probing	Assessed dichotomously within 15 seconds after probing	3 months
Other	Bleeding on probing	Assessed dichotomously within 15 seconds after probing	6 months
Other	Suppuration on probing	Assessed dichotomously post-probing	Baseline
Other	Suppuration on probing	Assessed dichotomously post-probing	3 months
Other	Suppuration on probing	Assessed dichotomously post-probing	6 months
Other	Probing depth	Defined as the distance in mm between the bottom of the pocket and the gingival margin	Baseline
Other	Probing depth	Defined as the distance in mm between the bottom of the pocket and the gingival margin	3 months
Other	Probing depth	Defined as the distance in mm between the bottom of the pocket and the gingival margin	6 months
Other	Recession	defined as the distance in mm between the amelocemental boundary and the gingival margin.	Baseline
Other	Recession	defined as the distance in mm between the amelocemental boundary and the gingival margin.	3 months
Other	Recession	defined as the distance in mm between the amelocemental boundary and the gingival margin.	6 months
Other	Number of teeth lost		Baseline
Other	Number of teeth lost		3 months
Other	Number of teeth lost		6 months
Other	Microbiological outcomes	Subgingival biofilm samples will be taken from samples of gingival crevicular fluid. DNA samples will be frozen at -20°C and preserved until further analysis by quantitative polymerase chain reaction (q-PCR) and 16S rRNA sequencing, using the Illumina MiSeq platform	Baseline
Other	Microbiological outcomes	Subgingival biofilm samples will be taken from samples of gingival crevicular fluid. DNA samples will be frozen at -20°C and preserved until further analysis by quantitative polymerase chain reaction (q-PCR) (Marín et al., 2019) and 16S rRNA sequencing, using the Illumina MiSeq platform	3 months
Other	Microbiological outcomes	Subgingival biofilm samples will be taken from samples of gingival crevicular fluid. DNA samples will be frozen at -20°C and preserved until further analysis by quantitative polymerase chain reaction (q-PCR) (Marín et al., 2019) and 16S rRNA sequencing, using the Illumina MiSeq platform	6 months
Other	Plasma levels of inflammatory mediators	Interleukin-1ß, Tumor Necrosis Factor-a, prostaglandin-E2, C reactive protein, D-Lactate and intestinal-type fatty acid binding protein 2 [FABP2]), lipopolysaccharide (LPS). matrix metalloproteinase (MMP)-9 levels, S-100B protein levels, quinolinic acid levels, and the ratio between kynurenic and quinolinic acid	Baseline
Other	Plasma levels of inflammatory mediators	Interleukin-1ß, Tumor Necrosis Factor-a, prostaglandin-E2, C reactive protein, D-Lactate and intestinal-type fatty acid binding protein 2 [FABP2]), lipopolysaccharide (LPS). matrix metalloproteinase (MMP)-9 levels, S-100B protein levels, quinolinic acid levels, and the ratio between kynurenic and quinolinic acid	3 months
Other	Plasma levels of inflammatory mediators	Interleukin-1ß, Tumor Necrosis Factor-a, prostaglandin-E2, C reactive protein, D-Lactate and intestinal-type fatty acid binding protein 2 [FABP2]), lipopolysaccharide (LPS). matrix metalloproteinase (MMP)-9 levels, S-100B protein levels, quinolinic acid levels, and the ratio between kynurenic and quinolinic acid	6 months
Other	Saliva samples	Oral 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 will be compared to phylogenetic and functional databases to obtain taxonomic and functional profiles.	Baseline
Other	Saliva samples	Oral 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 will be compared to phylogenetic and functional databases to obtain taxonomic and functional profiles.	3 months
Other	Saliva samples	Oral 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 will be compared to phylogenetic and functional databases to obtain taxonomic and functional profiles.	6 months
Other	Stool samples	Gut 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 will be compared to phylogenetic and functional databases to obtain taxonomic and functional profiles.	Baseline
Other	Stool samples	Gut 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 will be compared to phylogenetic and functional databases to obtain taxonomic and functional profiles.	3 months
Other	Stool samples	Gut 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 will be compared to phylogenetic and functional databases to obtain taxonomic and functional profiles.	6 months
Primary	Hamilton scale (HAM-D17)	Range: 0 to 52. The higher the score, the more severethe depressive symptoms	Baseline
Primary	Hamilton scale (HAM-D17)	Range: 0 to 52. The higher the score, the more severethe depressive symptoms	3 months
Primary	Hamilton scale (HAM-D17)	Range: 0 to 52. The higher the score, the more severethe depressive symptoms	6 months
Secondary	Childhood Trauma Questionnaire short form (CTQ-SF)	Range: 25 to 125. A higherscore means more (and worst) traumatic experience	Baseline
Secondary	Childhood Trauma Questionnaire short form (CTQ-SF)	Range: 25 to 125. A higherscore means more (and worst) traumatic experience	3 months
Secondary	Childhood Trauma Questionnaire short form (CTQ-SF)	Range: 25 to 125. A higherscore means more (and worst) traumatic experience	6 months
Secondary	UCLA Loneliness Scale (Spanish version)	Range: 20 to 80. Higher scores indicatehigher levels of loneliness	Baseline
Secondary	UCLA Loneliness Scale (Spanish version)	Range: 20 to 80. Higher scores indicatehigher levels of loneliness	3 months
Secondary	UCLA Loneliness Scale (Spanish version)	Range: 20 to 80. Higher scores indicatehigher levels of loneliness	6 months
Secondary	The World Health Organization Quality of Life questionnaire (WHOQOL)	Range: o to100. A higher score means better quality of life.	Baseline
Secondary	The World Health Organization Quality of Life questionnaire (WHOQOL)	Range: o to100. A higher score means better quality of life.	3 months
Secondary	The World Health Organization Quality of Life questionnaire (WHOQOL)	Range: o to100. A higher score means better quality of life.	6 months
Secondary	Beck Depression Inventory (BDI)	Range: 0 to 63. A higher score means more severe-depressive symptomatology	Baseline
Secondary	Beck Depression Inventory (BDI)	Range: 0 to 63. A higher score means more severe-depressive symptomatology	3 months
Secondary	Beck Depression Inventory (BDI)	Range: 0 to 63. A higher score means more severe-depressive symptomatology	6 months
Secondary	Centre for Epidemiologic Studies Depression scale [CES-D]	Range: 0 to 60. Higher scores indicate the presence of more severe symptomatology	Baseline
Secondary	Centre for Epidemiologic Studies Depression scale [CES-D]	Range: 0 to 60. Higher scores indicate the presence of more severe symptomatology	3 months
Secondary	Centre for Epidemiologic Studies Depression scale [CES-D]	Range: 0 to 60. Higher scores indicate the presence of more severe symptomatology	6 months
Secondary	Global Assessment of Functioning (GAF) Scale	Range: 1 to 100. A higher scoremeans better functioning. A score of 0 means Inadequate information.	Baseline
Secondary	Global Assessment of Functioning (GAF) Scale	Range: 1 to 100. A higher scoremeans better functioning. A score of 0 means Inadequate information.	3 months
Secondary	Global Assessment of Functioning (GAF) Scale	Range: 1 to 100. A higher scoremeans better functioning. A score of 0 means Inadequate information.	6 months