Impact of Periodontal Therapy on Mental Health Parameters (LeakBrainRCT)

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Depression; Periodontitis
• Intervention / Treatment: Procedure: Standard periodontal therapy (steps 1 & 2); Procedure: supragingival debridement with anesthesia (step 1)

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Elena Figuero, Prof.; Phone Number: 0034913942186; Email: elfiguer@ucm.es
• Study Contact Backup: Name: Juan Carlos Leza Cerro, Prof.; Phone Number: 0034913941478; Email: jcleza@ucm.es

Study Locations

• Spain
  • Madrid, Spain, 28034
    • Faculty of Dentistry, University Complutense of Madrid (UCM)
  • Madrid, Spain, 28040
    • Instituto de Psiquiatría y Salud Mental, Hospital Clínico San Carlos

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Subgingival therapy; 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.	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.
Other: Supragingival therapy; 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.	Procedure: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hamilton scale (HAM-D17)	Range: 0 to 52. The higher the score, the more severethe depressive symptoms	Baseline
Hamilton scale (HAM-D17)	Range: 0 to 52. The higher the score, the more severethe depressive symptoms	3 months
Hamilton scale (HAM-D17)	Range: 0 to 52. The higher the score, the more severethe depressive symptoms	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
UCLA Loneliness Scale (Spanish version)	Range: 20 to 80. Higher scores indicatehigher levels of loneliness	Baseline
Beck Depression Inventory (BDI)	Range: 0 to 63. A higher score means more severe-depressive symptomatology	Baseline
Centre for Epidemiologic Studies Depression scale [CES-D]	Range: 0 to 60. Higher scores indicate the presence of more severe symptomatology	Baseline
Childhood Trauma Questionnaire short form (CTQ-SF)	Range: 25 to 125. A higherscore means more (and worst) traumatic experience	Baseline
Childhood Trauma Questionnaire short form (CTQ-SF)	Range: 25 to 125. A higherscore means more (and worst) traumatic experience	3 months
Childhood Trauma Questionnaire short form (CTQ-SF)	Range: 25 to 125. A higherscore means more (and worst) traumatic experience	6 months
UCLA Loneliness Scale (Spanish version)	Range: 20 to 80. Higher scores indicatehigher levels of loneliness	3 months
UCLA Loneliness Scale (Spanish version)	Range: 20 to 80. Higher scores indicatehigher levels of loneliness	6 months
The World Health Organization Quality of Life questionnaire (WHOQOL)	Range: o to100. A higher score means better quality of life.	Baseline
The World Health Organization Quality of Life questionnaire (WHOQOL)	Range: o to100. A higher score means better quality of life.	3 months
The World Health Organization Quality of Life questionnaire (WHOQOL)	Range: o to100. A higher score means better quality of life.	6 months
Beck Depression Inventory (BDI)	Range: 0 to 63. A higher score means more severe-depressive symptomatology	3 months
Beck Depression Inventory (BDI)	Range: 0 to 63. A higher score means more severe-depressive symptomatology	6 months
Centre for Epidemiologic Studies Depression scale [CES-D]	Range: 0 to 60. Higher scores indicate the presence of more severe symptomatology	3 months
Centre for Epidemiologic Studies Depression scale [CES-D]	Range: 0 to 60. Higher scores indicate the presence of more severe symptomatology	6 months
Global Assessment of Functioning (GAF) Scale	Range: 1 to 100. A higher scoremeans better functioning. A score of 0 means Inadequate information.	Baseline
Global Assessment of Functioning (GAF) Scale	Range: 1 to 100. A higher scoremeans better functioning. A score of 0 means Inadequate information.	3 months
Global Assessment of Functioning (GAF) Scale	Range: 1 to 100. A higher scoremeans better functioning. A score of 0 means Inadequate information.	6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plaque index	presence/absence	Baseline
Plaque index	presence/absence	3 months
Plaque index	presence/absence	6 months
Bleeding on probing	Assessed dichotomously within 15 seconds after probing	Baseline
Bleeding on probing	Assessed dichotomously within 15 seconds after probing	3 months
Bleeding on probing	Assessed dichotomously within 15 seconds after probing	6 months
Suppuration on probing	Assessed dichotomously post-probing	Baseline
Suppuration on probing	Assessed dichotomously post-probing	3 months
Suppuration on probing	Assessed dichotomously post-probing	6 months
Probing depth	Defined as the distance in mm between the bottom of the pocket and the gingival margin	Baseline
Probing depth	Defined as the distance in mm between the bottom of the pocket and the gingival margin	3 months
Probing depth	Defined as the distance in mm between the bottom of the pocket and the gingival margin	6 months
Recession	defined as the distance in mm between the amelocemental boundary and the gingival margin.	Baseline
Recession	defined as the distance in mm between the amelocemental boundary and the gingival margin.	3 months
Recession	defined as the distance in mm between the amelocemental boundary and the gingival margin.	6 months
Number of teeth lost		Baseline
Number of teeth lost		3 months
Number of teeth lost		6 months
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
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
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
Plasma levels of inflammatory mediators	Interleukin-1β, Tumor Necrosis Factor-α, 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
Plasma levels of inflammatory mediators	Interleukin-1β, Tumor Necrosis Factor-α, 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
Plasma levels of inflammatory mediators	Interleukin-1β, Tumor Necrosis Factor-α, 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
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
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Universidad Complutense de Madrid
• Collaborators: Ministerio de Economía y Competitividad, Spain

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2024
• Primary Completion (Estimated): January 1, 2026
• Study Completion (Estimated): January 1, 2026

Study Registration Dates

• First Submitted: July 26, 2023
• First Submitted That Met QC Criteria: September 6, 2023
• First Posted (Actual): September 14, 2023

Study Record Updates

• Last Update Posted (Actual): January 9, 2024
• Last Update Submitted That Met QC Criteria: January 8, 2024
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Stomatognathic Diseases; Periodontal Diseases; Mouth Diseases; Depression; Periodontitis; Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics
• Other Study ID Numbers: URI 107-260623

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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