Oleanolic Acid as Therapeutic Adjuvant for Type 2 Diabetes Mellitus (OLTRAD STUDY)
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 100
- 试验地点
- 2
- 主要终点
- HbA1c
研究概览
简要总结
Oleanolic acid (OA), is a natural component of many plant food and medicinal herbs, which has shown to exert in experimental models hypoglycemic and hypolipidemic effects, and also a cytoprotective action against oxidative and chemotoxic stress underlying Type II Diabetes Mellitus (T2DM).Today it is known that OA shares mechanisms of action with metformin and other drugs of choice for the treatment of diabetes. Therefore, the OLTRAD (OLeanolic acid TReAtment for type 2 Diabetes) Study, a prospective, parallel group, randomized, double-blind, controlled trial with 100 participants, has been designed to demonstrate that the regular intake of an OA-enriched functional olive oil is effective as an adjuvant to metformin antidiabetic drug therapy. The hypothesis is that the inclusion of this functional olive oil in the diet will enhance the effects of the pharmacological treatment in diabetic patients, and may even reduce the need for prescription of such medications.
详细描述
TRIAL DESIGN The OLTRAD Study is a prospective, parallel group, randomized, double-blind, controlled trial designed to demonstrate that the regular intake of an OA-enriched functional olive oil is effective as an adjunct to metformin therapy (as monotherapy or in combination with other antidiabetic drugs) in the metabolic control of T2DM patients. The effect of the OA-enriched olive oil will be compared with that of the control oil, which consists of the same commercial olive oil not fortified in the triterpene.
A total of 100 volunteers of both sex will be selected from among the T2DM patients treated at the Endocrinology and Nutrition Service of the 'Virgen del Rocío' University Hospital (Seville, SPAIN).
SAMPLE SIZE CALCULATION Serum glycosylated hemoglobin (HbA1c) is adopted as the main quantitative variable for the analysis of glycemic control. The null hypothesis stated in the trial design is that the OA-based dietary intervention will reduce the baseline serum HbA1c levels of patients by at least 7%, compared to the control group. To test this one-sided hypothesis test with a 95% confidence level (α risk = 0.05) and 95% power (β risk = 0.05), a sample size of 44 volunteers per group is required. However, due to the characteristics of the study (a long-term lifestyle intervention), participant losses of up to 15% can be assumed, resulting in an adjusted sample size of 50 individuals per group.
RANDOMIZATION Once recruited, the 100 T2DM patients will be randomly assigned to one of the two study groups. Fifty individuals will be assigned to the intervention group, which will ingest the OA-enriched functional olive oil, whereas the other 50 volunteers will be assigned to the control group, which will receive the same non-enriched olive oil. At the time of admission, the study nursing staff will request by telephone the clinical coordinator of the trial (Principal Investigator 2 of the Project) the assignment of participants to the study groups (centralized randomization). Allocation to these groups will be made using computer generated tables of random numbers. Four randomization strata will be constructed by sex and age (cuttof 50 years).
INTERVENTION Participants will be instructed to ingest 55 mL/day of the assigned oil, preferably raw and freely distributed among the three main meals. Both the OA-enriched olive oil and the control oil will be delivered labeled with alphanumeric codes, the correspondence of which will only be known by the Principal Investigator 1 of the project. This ensures blinding of the clinical researchers and participants with respect to the type of olive oil assigned.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Both the OA-enriched olive oil and the control oil will be delivered labeled with alphanumeric codes, the correspondence of which will only be known by the Dr. Jose M. Castellano (Principal Investigator 1). This ensures blinding of the other researchers and trial participants with respect to the type of olive oil assigned.
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
- 否
入选标准
- •community-residing men and women aged.
- •Body Mass Index (BMI) between 25 and 39.9 kg/m
- •diagnosed with T2DM [Following the American Diabetes Association (ADA) 2019 criteria] at least six months before being included in this trial.
- •be treated with metformin (stable dose >= 850 mg/day at least three months before recruitment) as monotherapy, or in combination with other hypoglycemic agents (administration of insulin exclusively in a single basal dose), except pioglitazone and sulphonylureas.
- •HbA1c below 9% at baseline, with a variation compared with a prior HbA1c from at least three months before inclusion in this trial of less than +/- 0.5 %.
- •be able to give voluntary informed consent and willing to comply with all study procedures.
排除标准
- •suffering from Type 1 Diabetes Mellitus or latent autoimmune diabetes in adults.
- •suffering from chronic kidney disease (estimated glomerular filtration rate (eGFR) <30 ml/min/1.73m2).
- •suffering from acute or chronic hepatitis, signs and symptoms of any liver disease other than non-alcoholic fatty liver disease (NAFLD), or ALT/AST ratio >3 times the upper limit of the reference range.
- •To present, at the time of recruitment, allergies and intolerances associated with food consumption.
- •pregnant and lactating women.
- •lack of willingness to use a highly effective contraceptive method (in women of childbearing potential).
- •fasting triglyceridemia > 600 mg/dL despite adequate treatment.
- •grade 3 hypertension (systolic blood pressure ≥ 180 mm Hg and/or diastolic blood pressure ≥ 110 mm Hg) according to the 2018 guidelines of the European Society of Hypertension.
- •use of pioglitazone or sulfonylureas.
- •being treated with medications that promote weight loss (eg, Saxenda® [liraglutide 3.0 mg], Xenical® [orlistat], or similar over-the-counter [OTC] medications) within six months prior to the start of the trial.
- •Being on chronic (>14 days) therapy with systemic glucocorticoids (excluding topical, intraocular, intranasal, intra-articular, or inhaled preparations) within six months prior to enrollment.
- •Presenting any of the following cardiovascular conditions within 6 months prior to study entry: acute myocardial infarction, unstable angina, New York Heart Association (NYHA) class III or class IV heart failure, or cerebrovascular accident.
- •Evidence, in the investigators' opinion, of significant uncontrolled endocrine abnormality (e.g., thyrotoxicosis, adrenal crisis) at baseline.
- •History of active or untreated malignancy, or being in remission from a clinically significant malignancy (other than basal or squamous cell skin cancer, cervical carcinoma in situ, or prostate cancer in situ) during the last 5 years before the study entry.
- •Participation in the last 30 days in a clinical trial with an investigational product [if the previous investigational product has a long half-life, 3 months or 5 half-lives (whichever is longer) should have passed].
- •Being, at the time of recruitment, enrolled in any other clinical trial involving an investigational product or any other type of medical research that is not considered scientifically or medically compatible with this study.
- •Presence of any hematologic condition that may interfere with HbA1c measurement (eg, hemolytic anemias, sickle cell anemia).
- •History of any other condition (eg, known drug or alcohol abuse or psychiatric disorder, or any other physical or intellectual limitations), which, in the opinion of the investigator, may prevent the patient from following and completing the protocols.
结局指标
主要结局
HbA1c
时间窗: 1 year
The primary outcome of the trial is the evaluation of the glycemic control, assessed through the evolution of the plasma glycosylated hemoglobin (HbA1c) level, expressed in %
次要结局
- Plasma interleukine 1-beta(1 year)
- Plasma superoxide dismutase(1 year)
- Body mass index (BMI)(1 year)
- Waist circumference(1 year)
- Body composition - visceral fat mass(1 year)
- Serum C-peptide(1 year)
- Plasma lipoprotein A(1 year)
- Plasma bilirubin(1 year)
- Plasma levels of glutathion (GSH and GSSG)(1 year)
- Plasma adiponectin(1 year)
- Plasma ceruloplasmin(1 year)
- Hip circumference(1 year)
- Body composition - bone mass(1 year)
- Basal metabolism(1 year)
- HOMA-IR index(1 year)
- Plasma total cholesterol (CT)(1 year)
- Plasma low density lipoproteins (LDL)(1 year)
- Triglycerides in VLDL(1 year)
- Body composition - fat mass(1 year)
- Systolic blood pressure (SBP)(1 year)
- Pulse(1 year)
- Plasma triglycerides (TG)(1 year)
- Plasma alanine aminotransferase (ALT)(1 year)
- Plasma lactate dehydrogenase (LDH)(1 year)
- Body weight(1 year)
- Body height(1 year)
- Body composition - lean mass(1 year)
- Body composition - total water composition(1 year)
- Diastolic blood pressure (DBP)(1 year)
- Serum glucose(1 year)
- Serum insulin(1 year)
- Plasma high density lipoproteins (HDL)(1 year)
- Plasma creatinine(1 year)
- Plasma uric acid(1 year)
- Body composition - muscle mass(1 year)
- Plasma total lipoprotein B(1 year)
- Plasma aspartate aminotransferase (AST)(1 year)
- Plasma gamma-glutamyl transferase (GGT)(1 year)
- Plasma malondialdehyde(1 year)
- Plasma thyroid-stimulating hormone (TSH)(1 year)
- Serum fatty acids composition(1 year)
- Plasma leptin(1 year (measures at the time of recruitment and every three months thereafter))
- Plasma resistin(1 year)
- Plasma interleukine 6(1 year)
- Continuous blood glucose monitoring(1 year)
- Blood Count - red blood cells(1 year)
- Blood Count - leukocytes(1 year)
- Blood Count - lymphocytes(1 year)
- Blood Count - platelets(1 year)
- Leukocytes in urine(1 year)
- Plasma ultra-sensitive C-reactive protein(1 year)
- Plasma vitamin B12(1 year)
- Plasma levels of Oleanolic acid(1 year)
- Plasma ghrelin(1 year)
- Plasma tumor necrosis factor-alpha (TNF-alpha)(1 year)
- Blood Count - coagulative fibrinogen(1 year)
- Diglycerides in VLDL(1 year)
- Apo B in VLDL(1 year)
- Blood Count - eosinophils(1 year)
- Blood Count - basophils(1 year)
- Urine density(1 year)
- Urine creatinine(1 year)
- Urine albumin/creatinine ratio (UACR)(1 year)
- Plasma catalase(1 year)
- Blood Count - mean corpuscular hemoglobin(1 year)
- Blood Count - neutrophils(1 year)
- Glycosuria(1 year)
- Urine bilirubin(1 year)
- Phospholipids in VLDL(1 year)
- Fatty acids composition of VLDL(1 year)
- Blood Count - hematocrit(1 year)
- Blood Count - hemoglobin(1 year)
- Blood Count - mean corpuscular volume(1 year)
- Blood Count - monocytes(1 year)
- Blood Count - partial thromboplastin time(1 year)
- Blood Count - prothrombin time(1 year)
- Urine pH(1 year)
- Ketone bodies in urine(1 year)
- Urobilinogen(1 year)
- Presence of sediment in urine(1 year)
- Presence of nitrite in urine(1 year)
研究者
José M. Castellano, PhD
Principal Investigator
Spanish National Research Council