Nutraceuticals and Functional Foods of the Olive Tree of Interest in Aging and Its Pathologies: Study of Mechanisms of Action and Clinical Trial in Patients With Periodontitis
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 130
- 试验地点
- 1
- 主要终点
- Probing depth
研究概览
简要总结
Life expectancy has dramatically increased in the last century, although this process has not been always accompanied by an equivalent increase in healthy life expectancy. However, extending longevity without decreasing the risk of age-associated pathologies would not be desirable since non-communicable diseases can diminish seniors' quality of life, raise health-care costs, and increase pressure on family members who are responsible for their care. Maintaining a good health would help to ensure independence, security, and continued productivity in the later years helping both health systems and pensions lower costs. Thus, many scientific studies have tried to delay the age of onset of major age-related chronic diseases. In other words, research has been more focused on extending healthspan rather than lifespan.
Actually, numerous experimental studies have shown that the extension of lifespan by modifying risk factors is usually accompanied by delayed or reduced morbidity, including cardiovascular disease, neurodegeneration, and tumors. In the dietary context, modifications of the diet energy and/or macronutrient balance has shown to contribute to healthy aging, increasing healthspan and probably lifespan. Likewise, some foods would be able to supply a significant amount of compounds to the human diet, including non-nutrients which are thought to exert effects in the same sense. Thus, adequate nutritional intervention would be considered geroprotective interventions that would positively influence health by slowing basic biological processes of aging, such as cellular senescence, mitochondrial dysfunction, age-related decline of stress resistance, dysregulated cellular energy sensing/growth pathways, impaired proteostasis, deteriorated stem cell function/bioavailability, as well as inflammation/oxidative stress.
The use of nutraceuticals and functional foods from olive products and by-products can be useful in the treatment of pathologies associated with aging, such as periodontitis, as well as from the point of view of a proper nutrition during aging.
The study is a double-blind clinical trial of parallel design whose main objective is to evaluate the usefulness of a dietary supplement rich in oleuropein from the olive tree (leaf) in the adjuvant treatment of patients with age-related periodontitis. Efforts will be made to ensure that men and women be represented homogeneously in all study groups, although it is known that gender does not influence the appearance of periodontitis.
The experimental design foresees the inclusion of 130 patients with chronic periodontitis aged 60 years or older, 65 for the control group and 65 for the treatment group. Volunteers will be recruited from new patients attending the Faculty of Odontology at the University of Sevilla, Sevilla (Spain) by one study team member.
The investigational product will be provided by Natac Company (Madrid, Spain), a corporate group dedicated to researching, developing, manufacturing, and marketing natural ingredients to be used in food supplements, feed, pet food, as well as in functional foods, and as natural, active pharmaceutical ingredients.
The planned schedule for the participating subjects is as follows:
- Day 0: diagnosis of periodontitis, proposal to participate in the study, delivery of consent and information to the patient.
- Day 15: oral exams, collection of sociodemographic data, study of anthropometric characteristics and blood pressure, evaluation of eating habits, urine and blood sampling, collection of samples for the study of the periodontal microbiota and data collection and calculation of the index of successful ageing.
- Day 16 to 30 periodontal treatment.
- Day 16 to 136: administration of treatment (oleuropein or placebo).
- Day 136: oral exams, collection of sociodemographic data, study of anthropometric characteristics and blood pressure, evaluation of eating habits, urine and blood sampling, collection of samples for the study of the periodontal microbiota and data collection and calculation of the index of successful ageing.
The analytical part of the of the clinical trial will be developed mostly in the Biomedical Research Center (CIBM) of the University of Granada. The field part of the clinical trial in patients with periodontitis will be carried out at the Faculty of Dentistry of the University of Seville.
The design of the clinical trial provides for the participation of specialists from several disciplines, including specialists in Nutrition and Physiology, clinical specialists in Pathological Anatomy and Dentistry, technicians from the Center of Scientific Instrumentation of the University of Granada (specialists in various subjects such as microscopy, biochemical analysis, histology and veterinary) as well as technicians from the Marketing Unit of the OTRI of the University of Granada.
详细描述
To calculate the sample size, the GRANMO tool (https://www.imim.es/ofertadeserveis/software-public/granmo/) has been used, considering an alpha risk of 0.05, a bilateral contrast, a beta risk of 0.20, a standard deviation of differences of 2.5, a minimum difference of 1 mm reduction in probing depth to be detected between baseline and end of study, and a predicted proportion of loss of 20% tracking.
Treatments All patients will receive a complete oral examination at baseline and after 4 months following the treatment. Initial therapy will be performed in all patients and will consist on full-mouth scaling and root planning by hand and with ultrasonic instrumentation as necessary. This treatment will be completed with oral hygiene instructions. All initial therapy procedures will be performed by the same periodontist.
After periodontal treatment, enrolled volunteers will be randomly assigned to one of two groups by a second periodontist. Control group will receive hard gelatin capsules containing placebo (only the excipients), whereas the experimental group will receive the same hard gelatin capsules but containing 200 mg of an olive leaf extract. The randomization will be done by the use of random number charts (by coin-toss), which will be performed at the time of the first subject's enrollment, and the next subject will be assigned to the other group based on the first subject's assignment. Both placebo and capsules will be dispensed by the same person, and subjects will be given verbal and written instructions on its use. As volunteers will be enrolled they will be allocated sequential study numbers and provided with their capsules, sufficient for one month. Subjects will come to the Faculty every 4 weeks during the course of the trial to replenish their capsules. The capsules intake will last for a total of 4 months. Remaining medications will be checked for compliance. Capsules will be prepared at the CIDAF (Centro de Investigación Sobre Alimentos Funcionales) at the Technological Health Park in Granada. The olive extract will be obtained from Natac company (Madrid, España).
Sample collection and analyses All data collection and determinations will be performed at baseline and after 4 months.
A) Oral examinations Periodontal clinical measurements will include the presence or absence of supragingival dental plaque and gingival bleeding on probing (BOP), as well as periodontal probing depth (PPD) and recession of the gingival margin (GM). Parameters will be measured at six sites (mesiobuccal, buccal, distobuccal, distolingual, lingual, and mesiolingual) on every tooth by means of a calibrated periodontal probe (Hu-Friedy®, Chicago, IL, USA), 15 mm in length and 0.35 mm in diameter. Clinical attachment level (CAL) will be calculated by adding recession to PDD. The number of remaining teeth will also be recorded. O´Leary's plaque index, Van der Velden's bleeding index will be also calculated. Patients with BOP site <10%, PPD ≤3 mm, erythema and edema absence will be considered periodontal-healthy subjects.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Outcomes Assessor)
入排标准
- 年龄范围
- 50 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with periodontitis, defined as interdental attachment loss in ≥2 non-adjacent teeth or lingual or buccal attachment loss ≥3 mm in ≥2 teeth.
排除标准
- •Patients taking antimicrobial drugs in the previous 6 months or anti-inflammatory drugs during the previous 2 months,
- •Patients taking regular vitamin supplementation,
- •Patients receiving treatment for any periodontal condition,
- •Patients with any autoimmune disease,
- •Patients with any disease affecting oral mucosa,
- •Patients with any systemic disease affecting bone metabolism,
- •Patients with aggressive disease,
- •Patients with physical or mental disability or unable to provide informed consent,
- •Patients unable to swallow capsules,
- •Patients at risk of complications from periodontal therapy.
研究组 & 干预措施
Placebo
Patients will receive hard gelatin capsules containing placebo (only the excipients).
干预措施: Placebo (Dietary Supplement)
Oleuropein
Patients will receive the same hard gelatin capsules but containing 200 mg of an olive leaf extract.
干预措施: Oleuropein from olive tree (Dietary Supplement)
结局指标
主要结局
Probing depth
时间窗: 120 days
Change of 2 mm or more
次要结局
- Attachment level(120 days)
- Gum bleeding(120 days)
研究者
Jose Luis Quiles Morales
Full Professor
Universidad de Granada