Effect of Implant Treatment and/or Dietary Advice on the Nutrition of Edentulous Ageing Subjects

Study Overview
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Brief Summary
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Loss of masticatory function consequent to tooth loss is associated with changes in food choices and insufficient nutrition intake. To date, studies showed no significant improvement in nutrient intake with interventions based solely on dental prostheses. Pilot studies have shown positive impacts of interventions combining implant-supported fixed dental prosthesis with brief dietary interventions. The relative contribution and the potential synergy of the components of such interventions need to be determined as it has major public health implications for the community-dwelling ageing population that continues to disproportionately suffer from tooth loss and its consequences. This study tests the effect of rehabilitation of masticatory function with fixed implant supported dentures and diet re-education on the dietary intake and nutrition in older subjects with terminal dentition (stage IV periodontitis) or full edentulism. A 2 × 2 factorial randomized controlled trial of eligible adult (≥60 years) with loss of masticatory function consequent to full arch edentulism or terminal dentition (n = 120) will be conducted to test whether the rehabilitation of masticatory function with fixed implant supported dentures, diet re-education and/or their combination improves the diet and nutrition of ageing subjects. The study has been designed to detect changes in fruit and vegetable intake at 4 months using the 24-hour dietary recall method. Changes in protein as percentage of total energy, nutritional biomarkers, metabolomics, oral and gut microbiome, quality of life and masticatory function will also be assessed.

Detailed Description
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Complete edentulism or presence of a terminal dentition that is functionally compromised in an irreparable way represent the end of the spectrum of caries and periodontitis, eventually leading to loss of masticatory function. These subjects tend to show change in their diet behavior choosing softer diets with higher carbohydrates and fat and less fresh fruit and vegetables. Accumulating evidence points to the presence of an association between changes in dietary behavior consequent to tooth loss and insufficient nutrition intake. Such impaired nutrition may have long term effects on muscle strength and physical decline, and be detrimental to general health. Indeed, the recent GBD study of dietary risk factors identifies 15 important disease associated exposures. Their analysis shows that 5 of the health associated exposures: consumption of fruit, vegetables, whole grains, nuts, and fiber require a good level of mastication. While the physiology of mastication is an essential component of alimentation and contributes to the broader process of nutrition, a more holistic approach is needed to properly establish the scientific basis of the contribution of oral health to nutrition and healthy ageing. Assuming a potential cause-effect relationship between the inadequate food choice consequent to tooth loss and compromised nutrition intake, several studies have tried to improve the nutrient intake among edentulous individuals with various types of dentures. However, this goal has not been readily achieved with either complete denture or implant-retained overdenture, given the function limitation on these prosthesis and the lack of dietary intervention. A small-scale case series has shown that implant-supported fixed prosthesis resulted in more efficient mastication and improved nutrient intake compared with conventional and implant-based removable dentures in partial edentulism. However, no evidence is available regarding the effect of re-establishment of masticatory function with an implant-supported fixed prosthesis in edentulous patients. Moreover, with the increasing evidence suggesting a positive impact of nutrition counselling on the dietary intake, brief dietary advice has been advocated to help patients make full use of the enhanced masticatory function to improve their diet. Ellis et al. further showed that the impact of dietary advice on patient's satisfaction with dentures and oral health-related quality of life depends on the nature of the prosthesis. No trial has been performed to assess the benefit of dietary advice only or the combined effect of re-establishment of masticatory function with an implant-supported fixed prosthesis and dietary advice in edentulous elderly subjects. This is a 2 × 2 factorial clinical trial aimed to assess the effect of rehabilitation of masticatory function with fixed implant supported dentures and simultaneous diet re-education on the diet intake and nutrition in ageing subjects with terminal dentition (stage IV periodontitis) or full edentulism.

Official Title
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Does the Rehabilitation of Masticatory Function and/or Brief Dietary Advice Improve the Diet and Nutrition of Older Subjects With Terminal Dentition or Full Edentulism? A Factorial Randomized Controlled Clinical Trial

Conditions
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Edentulous Jaw, Periodontitis

Intervention / Treatment
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* Procedure: Implant-supported full-arch fixed dental prostheses（dental intervention,DE）
* Behavioral: Dietary intervention tailored to the dental status (dietary intervention, DI)
* Procedure: Delayed implant-supported full-arch fixed dental prostheses（dental intervention,DE）
* Behavioral: Delayed dietary intervention tailored to the dental status (dietary intervention, DI)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: being edentulous or having the presence of terminal dentition (defined as few remaining teeth insufficient in terms of number, position and health status to provide adequate anchorage to a tooth supported or a tooth retained denture) and looking for implant-supported fixed denture treatment accepted treatment plan for fixed implant-supported prosthesis restoring at least 10 pairs of occluding teeth self-reported inadequate vegetable or fruit or protein intakes (patients were included if at least one of the three criteria listed below were met) I. Patients with a total average daily intake of < 80 g of poultry, meat and aquatic product. II. Patients with an average daily intake of < 200 g of fruit. III. Patients with an average daily intake of < 300 g of vegetables. understand written and spoken Chinese and who could respond to Chinese questionnaires able and willing to give informed consent for participation in the study able and willing to comply with 12-month follow-up Exclusion Criteria: general contraindications to elective oral surgery procedures local contraindications to implant-supported immediate-loading fixed prosthesis (e.g. limited jaw opening, insufficient bone volumes/densities) looking for replacement of existing implant-retained overdenture with implant-supported fixed denture treatment presence of infectious disease, acute or chronic symptoms of TMJ disorder psychiatric disorder, dementia any dietary restriction, currently taking nutrient supplements or inability to choose his/her diet. uncontrolled diabetes (HbA1c≥7.0%) self-reported heavy smokers (>10 cigarette/day)

Ages Eligible for Study
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Minimum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Interventional Model Description: 2x2 factorial design (4 month follow up) and longitudinal follow-up to 12 months
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GroupA（DE+/DI+）<br>The treatment includes the combination of implant-supported full-arch fixed prostheses (dental intervention, DE) and dietary intervention tailored to the dental status (dietary intervention, DI) without waiting period | Procedure: Implant-supported full-arch fixed dental prostheses（dental intervention,DE）<br>* Implant-supported full-arch fixed dental prostheses in at least one jaw and appropriate treatment in the opposing jaw regarding periodontal diseases, caries, replacement of missing teeth and soft tissue disorders to get at least 10 pairs of occluding teeth. The intervention is designed to provide rehabilitation of masticatory function.<br>* Other names: Immediate rehabilitation of masticatory function;Behavioral: Dietary intervention tailored to the dental status (dietary intervention, DI)<br>* Dietary intervention based on the health Belief Model (HBM) with the behavioral goal of increasing an individual's likelihood of food intake regarding fresh vegetables, fresh fruits, and high quality protein for the potential intervention strategies. Participants will receive 20 minutes' coordinated dietary advice in the form of the slideshow presentation . A pamphlet prepared with reference to the Supplementary Guidelines for Elderly Populations, the 4th edition of the Dietary Guidelines for Chinese will be given to the participant separately. If a participant does not prepare his or her own meals, the person who does the cooking receives the dietary advice as well.<br>* Other names: Immediate dietary intervention;|
| Active Comparator: GroupB（DE+/DI-）<br>The treatment includes implant-supported full-arch fixed prostheses (dental intervention, DE) without waiting period and dietary intervention tailored to the dental status (dietary intervention, DI) 4-month later | Procedure: Implant-supported full-arch fixed dental prostheses（dental intervention,DE）<br>* Implant-supported full-arch fixed dental prostheses in at least one jaw and appropriate treatment in the opposing jaw regarding periodontal diseases, caries, replacement of missing teeth and soft tissue disorders to get at least 10 pairs of occluding teeth. The intervention is designed to provide rehabilitation of masticatory function.<br>* Other names: Immediate rehabilitation of masticatory function;Behavioral: Delayed dietary intervention tailored to the dental status (dietary intervention, DI)<br>* Dietary intervention based on the health Belief Model (HBM) with the behavioral goal of increasing an individual's likelihood of food intake regarding fresh vegetables, fresh fruits, and high quality protein for the potential intervention strategies. Participants will receive 20 minutes' coordinated dietary advice in the form of the slideshow presentation . A pamphlet prepared with reference to the Supplementary Guidelines for Elderly Populations, the 4th edition of the Dietary Guidelines for Chinese will be given to the participant separately. If a participant does not prepare his or her own meals, the person who does the cooking receives the dietary advice as well.<br>* Other names: Delayed dietary intervention;|
| Active Comparator: GroupC（DE-/DI+）<br>The treatment includes dietary intervention tailored to the dental status (dietary intervention, DI) without waiting period and implant-supported full-arch fixed prostheses (dental intervention, DE) 4-month later | Behavioral: Dietary intervention tailored to the dental status (dietary intervention, DI)<br>* Dietary intervention based on the health Belief Model (HBM) with the behavioral goal of increasing an individual's likelihood of food intake regarding fresh vegetables, fresh fruits, and high quality protein for the potential intervention strategies. Participants will receive 20 minutes' coordinated dietary advice in the form of the slideshow presentation . A pamphlet prepared with reference to the Supplementary Guidelines for Elderly Populations, the 4th edition of the Dietary Guidelines for Chinese will be given to the participant separately. If a participant does not prepare his or her own meals, the person who does the cooking receives the dietary advice as well.<br>* Other names: Immediate dietary intervention;Procedure: Delayed implant-supported full-arch fixed dental prostheses（dental intervention,DE）<br>* Delayed (4 months) implant-supported full-arch fixed dental prostheses in at least one jaw and appropriate treatment in the opposing jaw regarding periodontal diseases, caries, replacement of missing teeth and soft tissue disorders to get at least 10 pairs of occluding teeth. The intervention is designed to provide rehabilitation of masticatory function.<br>* Other names: Delayed rehabilitation of masticatory function;|
| Placebo Comparator: GroupD（DE-/DI-）<br>The treatment included implant-supported full-arch fixed prostheses (dental intervention, DE) and dietary intervention tailored to the dental status (dietary intervention, DI) with 4-month waiting period. Only general dietary information is provided at baseline. | Procedure: Delayed implant-supported full-arch fixed dental prostheses（dental intervention,DE）<br>* Delayed (4 months) implant-supported full-arch fixed dental prostheses in at least one jaw and appropriate treatment in the opposing jaw regarding periodontal diseases, caries, replacement of missing teeth and soft tissue disorders to get at least 10 pairs of occluding teeth. The intervention is designed to provide rehabilitation of masticatory function.<br>* Other names: Delayed rehabilitation of masticatory function;Behavioral: Delayed dietary intervention tailored to the dental status (dietary intervention, DI)<br>* Dietary intervention based on the health Belief Model (HBM) with the behavioral goal of increasing an individual's likelihood of food intake regarding fresh vegetables, fresh fruits, and high quality protein for the potential intervention strategies. Participants will receive 20 minutes' coordinated dietary advice in the form of the slideshow presentation . A pamphlet prepared with reference to the Supplementary Guidelines for Elderly Populations, the 4th edition of the Dietary Guidelines for Chinese will be given to the participant separately. If a participant does not prepare his or her own meals, the person who does the cooking receives the dietary advice as well.<br>* Other names: Delayed dietary intervention;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| changes in intake of fruit and vegetables | Three 24-hour dietary recall will be conducted through interview, twice on weekdays and once on weekend. The data on food consumption will be converted into the corresponding nutrient contents based on the China Food Composition Tables Standard Edition | from baseline to 4-month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Nutrient intake | The intake of fruit and vegetables, protein% of total energy according to a modified version of food-frequency questionnaire | at baseline, 4, 8, 12 and 16 months | 
| Masticatory function | Ability to mix a two-color chewing gum with 20 masticatory cycles. The obtained bolus will be pressed to a standardized height and a color image will be acquired. Quantitative data will be obtained by digital analysis of the image using variance of hue as the outcome | at baseline, 4, 8, 12 and 16 months | 
| Peri-implant oral hygiene | Modified plaque index (mPI) measured by periodontal probing | at 4, 8, 12 and 16 months for groups with implants | 
| Peri-implant soft and hard tissue health (probing depth) | Peri-implant probing depth (PD) measured by periodontal probing | at 4, 8, 12 and 16 months for groups with implants | 
| Peri-implant soft and hard tissue health (local inflammation) | Peri-implant modified bleeding index (mBI) measured by periodontal probing | at 4, 8, 12 and 16 months for groups with implants | 
| Peri-implant radiographic bone level stability | Standardized panoramic radiographic imaging will be conducted to assess the peri-implant bone level. | 4, and 12 months after dental implant placement (in the context of standard care) | 
| OHIP-14 questionnaire | the impact of oral health on the quality of life of participants assessed with the oral health impact profile (OHIP)-14. A 5-point scale was used to calculate the score for each of 14 items. The total score of OHIP-14 is in the range of 0 to 56 with higher values indicating more frequent impacts | at baseline, 4, 8, 12 and 16 months | 
| Metabolism and systemic inflammatory biomarkers (i) | blood plasma concentration of homocysteine (gas chromatography) | at baseline, 4, 8, 12 and 16 months | 
| Metabolism and systemic inflammatory biomarkers (ii) | Plasma hs-CRP assessed by immunoturbidometry | at baseline, 4, 8, 12 and 16 months | 
| Metabolism and systemic inflammatory biomarkers (iii) | Plasma TNF-α (ELISA) | at baseline, 4, 8, 12 and 16 months | 
| Metabolism and systemic inflammatory biomarkers (iv) | Plasma IL-1β (ELISA) | at baseline, 4, 8, 12 and 16 months | 
| Metabolism and systemic inflammatory biomarkers (v) | Plasma IL-6 (ELISA) | at baseline, 4, 8, 12 and 16 months | 
| Oxidative stress biomarkers (i) | Plasma Co Q10 with liquid chromatography-mass spectrometry | at baseline, 4, 8, 12 and 16 months | 
| Oxidative stress biomarkers (ii) | Plasma uric acid (the enzymatic method) | at baseline, 4, 8, 12 and 16 months | 
| Oxidative stress biomarkers (iii) | Plasma superoxide dismutase (the chemical colorimetric method) | at baseline, 4, 8, 12 and 16 months | 
| Nutritional biomarker（Plasma vitamin A） | concentration of plasma vitamin A assessed by liquid chromatography-mass spectrometry | at baseline, 4, 8, 12 and 16 months | 
| Nutritional biomarker（Plasma vitamin B2） | concentration of plasma vitamin B2 assessed by liquid chromatography-mass spectrometry | at baseline, 4, 8, 12 and 16 months | 
| Nutritional biomarker（Plasma vitamin B12） | concentration of plasma vitamin B12 assessed by liquid chromatography-mass spectrometry | at baseline, 4, 8, 12 and 16 months | 
| Nutritional biomarker（Plasma folate） | concentration of plasma folate assessed by liquid chromatography-mass spectrometry | at baseline, 4, 8, 12 and 16 months | 
| Nutritional biomarker（Plasma vitamin C） | concentration of plasma vitamin C assessed by liquid chromatography-mass spectrometry | at baseline, 4, 8, 12 and 16 months | 
| Nutritional biomarker（Plasma vitamin E） | concentration of plasma vitamin E assessed by liquid chromatography-mass spectrometry | at baseline, 4, 8, 12 and 16 months | 
| Nutritional biomarker（plasma α-carotene） | concentration of plasma α-carotene assessed by liquid chromatography-mass spectrometry | at baseline, 4, 8, 12 and 16 months | 
| Nutritional biomarker（plasma β-carotene） | concentration of plasma α-carotene assessed by liquid chromatography-mass spectrometry | at baseline, 4, 8, 12 and 16 months | 
| Nutritional biomarker（plasma β-cryptoxanthin） | concentration of plasma β-cryptoxanthin assessed by liquid chromatography-mass spectrometry | at baseline, 4, 8, 12 and 16 months | 
| Nutritional biomarker（plasma lycopene） | concentration of plasma lycopene assessed by liquid chromatography-mass spectrometry | at baseline, 4, 8, 12 and 16 months | 
| Nutritional biomarker（plasma lutein/zeaxanthin） | concentration of plasma lutein/zeaxanthin assessed by liquid chromatography-mass spectrometry | at baseline, 4, 8, 12 and 16 months | 
| Nutritional biomarker（plasma α-tocopherols） | concentration of plasma α-tocopherols assessed by liquid chromatography-mass spectrometry | at baseline, 4, 8, 12 and 16 months | 
| Nutritional biomarker（plasma γ-tocopherols） | concentration of plasma γ-tocopherols assessed by liquid chromatography-mass spectrometry | at baseline, 4, 8, 12 and 16 months | 
| Nutritional biomarker（Plasma total cholesterol） | concentration of plasma total cholesterol (Enzymatic Measurements) | at baseline, 4, 8, 12 and 16 months | 
| Nutritional biomarker（Plasma HDL cholesterol） | concentration of plasma HDL cholesterol (Enzymatic Measurements) | at baseline, 4, 8, 12 and 16 months | 
| Nutritional biomarker（Plasma LDL cholesterol） | concentration of plasma LDL cholesterol (Enzymatic Measurements) | at baseline, 4, 8, 12 and 16 months | 
| Nutritional biomarker（Plasma triglycerides） | concentration of plasma triglycerides (Enzymatic Measurements) | at baseline, 4, 8, 12 and 16 months | 
| Nutritional biomarker（Plasma Lpa） | concentration of plasma Lpa (Enzymatic Measurements) | at baseline, 4, 8, 12 and 16 months | 
| Metabolomics (Metabolites) | Profiling of annotated plasma metabolites (Differential plasma metabolites with P-value< 0.05 and fold change≥2 or FC≤0.5) based on untargeted metabolomics using liquid chromatography coupled with mass spectrometry analyses | at baseline, 4, 8, 12 and 16 months | 
| Metabolomics (Oxylipidomics) | Profiling of annotated plasma lipid metabolites (Differential lipid metabolites with P-value< 0.05 and fold change≥2 or FC≤0.5) based on untargeted metabolomics using liquid chromatography coupled with mass spectrometry analyses | at baseline, 4, 8, 12 and 16 months | 
| Microbiome Analysis(saliva) | Taxonomic profiling with 16S rRNA gene sequencing in saliva samples | at baseline, 4, 8, 12 and 16 months | 
| Microbiome Analysis(plaque) | Taxonomic profiling with 16S rRNA gene sequencing in subgingival plaque samples | at baseline, 4, 8, 12 and 16 months | 
| Microbiome Analysis(stool) | Taxonomic profiling with 16S rRNA gene sequencing in stool samples | at baseline, 4, 8, 12 and 16 months | 
| Nutritional status | assessment by Mini-nutrient status form with a score of 12-14 corresponding to normal nutritional status；8-11 at risk of malnutrition；0-7 malnourished | at baseline, 4, 8, 12 and 16 months | 
| Muscle strength | muscle strength assessed by Hand grip dynamometer | at baseline, 4, 8, 12 and 16 months | 
| Cognitive function(i) | cognitive function assessed with the Mini-Mental State Examination with a total score of 30. Score 27-30: normal cognition；Score 21-26: mild cognitive impairment；Score 10-20: moderate cognitive impairment；Score <10: severe cognitive impairment | at baseline, 4, 8, 12 and 16 months | 
| Cognitive function(ii) | dementia screening with the Alzheimer's disease eight-item tool. With Score 0: no cognitive impairment, Score 1-2: cognitive impairment; Score>=3: dementia | at baseline, 4, 8, 12 and 16 months | 
| Depression symptoms | assessment with the shortened Center for Epidemiologic Studies Depression Scale. The total score is the sum of 10 items. A score equal to or above 10 is considered depressed. | at baseline, 4, 8, 12 and 16 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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nutrition, implant-supported fixed prosthesis, diet intake, healthy ageing, masticatory function