Multiomic Evaluation of the Effect of Artichoke By-products Supplementation Rich in Hydroxycinnamic Acids, Integrated Into an Energy-restricted Mediterranean Diet, on the Prevention of Type 2 Diabetes.
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 150
- 试验地点
- 1
- 主要终点
- Change in HOMA-IR and body weight
研究概览
简要总结
The ARTI-UP study evaluates whether daily consumption of a supplement made from artichoke by-products, rich in hydroxycinnamic acids (HCAs), in combination with an energy-restricted Mediterranean diet (erMeDiet), can improve glycaemic control, reduce insulin resistance and contribute to weight loss in subjects with overweight or obesity. In addition, it seeks to understand the biological mechanisms involved using omic techniques and to establish predictive biomarkers that will enable progress towards personalised nutrition strategies.
详细描述
Type 2 diabetes (T2D) and obesity represent major global public health challenges, largely driven by insulin resistance and excess body weight. Lifestyle interventions based on energy-restricted Mediterranean dietary patterns have demonstrated beneficial effects on glycemic control and body weight; however, substantial interindividual variability in response persists. Emerging evidence suggests that specific dietary bioactive compounds, such as hydroxycinnamic acids (HCAs), may play a relevant role in improving insulin sensitivity, yet their contribution within structured dietary interventions remains insufficiently explored.
In this context, the hypothesis of the present study is that daily supplementation with an artichoke by-product powder rich in bioavailable HCAs, administered within an energy-restricted Mediterranean diet (erMeDiet), will lead to greater improvements in insulin resistance and body weight compared with an erMeDiet alone in overweight and obese adults with insulin resistance. Furthermore, interindividual variability in response to HCAs is hypothesized to be partially explained by differences in metabolic, microbiota-related, and epigenetic profiles.
Following recruitment and screening, the study will consist of a 16-week randomized, controlled, double-blind, parallel-group lifestyle intervention. Participants will be randomly assigned (1:1) to one of two intervention arms:
Intervention group: Energy-restricted Mediterranean diet (approximately -500 kcal/day) combined with physical activity counselling and daily supplementation with an artichoke by-product powder providing a minimum of 600 mg/day of bioavailable hydroxycinnamic acids.
Control group: Energy-restricted Mediterranean diet and identical physical activity counselling, supplemented with an isocaloric placebo powder matched for macronutrient composition but devoid of HCAs.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •BMI between 25.0 and 35.0 kg/m²
- •HOMA-IR ≥ 2.
- •Adequate physical examination and vital signs or clinically irrelevant to the intervention (those not related to metabolic health).
- •Subjects must be able to understand and be willing to sign the informed consent form, and must comply with all study procedures and requirements.
- •Subjects must have a stable means of communication, either by email and/or telephone.
排除标准
- •Weight loss of more than 5% in the last 6 months prior to surgery.
- •Consumption of antibiotics in the 3 months prior to the intervention.
- •Subjects who are undergoing treatment for weight loss/body composition modification, use medication for weight loss or blood glucose control, or have had weight loss surgery.
- •Have a medical diagnosis of type 1 or type 2 diabetes.
- •History of inflammatory bowel disease and/or resection of the large or small intestine. Subjects with relevant functional or structural abnormalities of the digestive system.
- •Inability to follow the recommended diet or physical exercise.
- •Unavailability in terms of time or location to attend study visits.
- •Failure to sign the informed consent form.
- •Inability to communicate with the research team.
- •Endocrine-related excess weight (except for treated hypothyroidism, at least 3 months of stable treatment).
- •Being pregnant or planning a pregnancy during the intervention period.
- •Being breastfeeding.
- •Having an allergy to artichokes.
- •Severe psychiatric illnesses that have required hospitalisation in the last 6 months.
- •Renal failure.
- •Having immunodeficiency or being HIV positive.
- •Being treated with immunosuppressive drugs or cytotoxic agents.
- •High alcohol intake: more than 14 units (women) and 20 units (men) per week.
- •Participation in another randomised clinical trial.
- •Volunteers undergoing drug treatment for less than 3 months with a stable dose/stable treatment.
- •Taking nutritional supplements (supplements: plant derivatives, for weight loss, fibre and probiotics) unless the person is willing to stop taking them for 3 months prior to the start of the trial.
- •Taking nutritional supplements (supplements: plant-derived, for weight loss, fibre and probiotics) unless the person is willing to stop taking them for the 16 weeks of the study intervention and a minimum washout period of 14 days prior to baseline measurements is guaranteed.
- •Having donated blood in the 14 days prior to the baseline visit.
- •Subjects with any type of cancer or undergoing treatment for cancer, or who have not been in remission for at least 5 years.
- •Any other condition that may interfere with adherence to the intervention.
研究组 & 干预措施
Intervention group: erMeDiet + artichoke capsules
Participants will follow a energy-restricted Mediterranean diet and consume artichoke by-product capsules daily for 16 weeks.
干预措施: Artichoke by-product capsules (Dietary Supplement)
Intervention group: erMeDiet + artichoke capsules
Participants will follow a energy-restricted Mediterranean diet and consume artichoke by-product capsules daily for 16 weeks.
干预措施: Energy-restricted Mediterranean diet (erMeDiet) (Behavioral)
Intervention group: erMeDiet + artichoke capsules
Participants will follow a energy-restricted Mediterranean diet and consume artichoke by-product capsules daily for 16 weeks.
干预措施: Physical activity (Behavioral)
Control group: erMeDiet + placebo capsules
Participants will follow an energy-restricted Mediterranean diet and consume placebo capsules daily for 16 weeks.
干预措施: Energy-restricted Mediterranean diet (erMeDiet) (Behavioral)
Control group: erMeDiet + placebo capsules
Participants will follow an energy-restricted Mediterranean diet and consume placebo capsules daily for 16 weeks.
干预措施: Placebo capsules (Dietary Supplement)
Control group: erMeDiet + placebo capsules
Participants will follow an energy-restricted Mediterranean diet and consume placebo capsules daily for 16 weeks.
干预措施: Physical activity (Behavioral)
结局指标
主要结局
Change in HOMA-IR and body weight
时间窗: From enrollment to the end of treatment at 16 weeks.
Formula: fasting insulin (microU/L) x fasting glucose (nmol/L)/22.5 30. HOMA-IR is a good measurement of insulin resistance since it has a very good correlation with the gold standard test hyperinsulinemic-euglycemic clamp (r\>0.88, p\<0.0001).
次要结局
- Fasting glucose (mmol/L)(From enrollment to the end of treatment at 16 weeks.)
- Fasting insulin (µU/mL)(From enrollment to the end of treatment at 16 weeks.)
- HbA1c (%)(From enrollment to the end of treatment at 16 weeks.)
- HOMA-IR Index(From enrollment to the end of treatment at 16 weeks.)
- HOMA-B index(From enrollment to the end of treatment at 16 weeks.)
- Gut microbial diversity(From enrollment to the end of treatment at 16 weeks.)
- Gut microbiota taxonomic composition(From enrollment to the end of treatment at 16 weeks.)
- Microbial functional pathways related to metabolic health(From enrollment to the end of treatment at 16 weeks.)
- Urinary polyphenol-derived metabolites (mmol/24 h).(From enrollment to the end of treatment at 16 weeks.)
- Urinary metabolomic profile(From enrollment to the end of treatment at 16 weeks.)
- Epigenome-wide DNA methylation analysis(From enrollment to the end of treatment at 16 weeks.)
- Differentially methylated CpG sites (Δβ-value)(From enrollment to the end of treatment at 16 weeks.)
- Epigenetic age acceleration (years)(From enrollment to the end of treatment at 16 weeks.)
- Body Mass Index (BMI) (kg/m²)(From enrollment to the end of treatment at 16 weeks.)
- Waist circumference (cm)(From enrollment to the end of treatment at 16 weeks.)
- Fat mass (kg)(From enrollment to the end of treatment at 16 weeks.)
- Fat mass (%)(From enrollment to the end of treatment at 16 weeks.)
- Visceral Adipose Tissue (VAT) (g or cm²)(From enrollment to the end of treatment at 16 weeks.)
- Total cholesterol (mmol/L)(From enrollment to the end of treatment at 16 weeks.)
- Low-density lipoprotein cholesterol (LDL-c) (mmol/L)(From enrollment to the end of treatment at 16 weeks.)
- High-density lipoprotein cholesterol (HDL-c) (mmol/L)(From enrollment to the end of treatment at 16 weeks.)
- Triglycerides (mmol/L)(From enrollment to the end of treatment at 16 weeks.)
- C-reactive protein (CRP) (mg/L)(From enrollment to the end of treatment at 16 weeks.)
- Tumor necrosis factor-alpha (TNF-α) (pg/mL)(From enrollment to the end of treatment at 16 weeks.)
- Interleukin-6 (IL-6) (pg/mL)(From enrollment to the end of treatment at 16 weeks.)
- Oxidized LDL (LDLox) (U/L)(From enrollment to the end of treatment at 16 weeks.)
- Alanine transaminase (ALT) (U/L)(From enrollment to the end of treatment at 16 weeks.)
- Aspartate aminotransferase (AST) (U/L)(From enrollment to the end of treatment at 16 weeks.)
- Gamma-glutamyl transpeptidase (GGT) (U/L)(From enrollment to the end of treatment at 16 weeks.)
- Blood urea (mmol/L)(From enrollment to the end of treatment at 16 weeks.)
- Blood creatinine (µmol/L)(From enrollment to the end of treatment at 16 weeks.)
- Estimated Glomerular Filtration Rate (eGFR) (mL/min/1.73 m²)(From enrollment to the end of treatment at 16 weeks.)
- Blood albumin (g/L)(From enrollment to the end of treatment at 16 weeks.)
- Uric acid (µmol/L)(From enrollment to the end of treatment at 16 weeks.)
- Total intervention adherence (%)(From enrollment to the end of treatment at 16 weeks.)
研究者
Sonia García Calzón
Principal Investigator
Clinica Universidad de Navarra, Universidad de Navarra