xml: <clinical_study>
    <!-- This xml conforms to an XML Schema at:
      https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
    <required_header>
      <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
      <link_text>Link to the current ClinicalTrials.gov record.</link_text>
      <url>https://clinicaltrials.gov/ct2/show/NCT06030544</url>
    </required_header>
    <id_info>
      <org_study_id>PID2019-107837RB-I00</org_study_id>
      <nct_id>NCT06030544</nct_id>
    </id_info>
    <brief_title>Oleanolic Acid as Therapeutic Adjuvant for Type 2 Diabetes Mellitus (OLTRAD STUDY)</brief_title>
    <acronym>OLTRAD</acronym>
    <official_title>Oleanolic Acid as Therapeutic Adjuvant for Type 2 Diabetes Mellitus (OLTRAD STUDY)</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Spanish National Research Council</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Andalusian Health Service</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Universidad Pablo de Olavide</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Spanish National Research Council</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        Oleanolic acid (OA), is a natural component of many plant food and medicinal herbs, which has&#xD;
        shown to exert in experimental models hypoglycemic and hypolipidemic effects, and also a&#xD;
        cytoprotective action against oxidative and chemotoxic stress underlying Type II Diabetes&#xD;
        Mellitus (T2DM).Today it is known that OA shares mechanisms of action with metformin and&#xD;
        other drugs of choice for the treatment of diabetes. Therefore, the OLTRAD (OLeanolic acid&#xD;
        TReAtment for type 2 Diabetes) Study, a prospective, parallel group, randomized,&#xD;
        double-blind, controlled trial with 100 participants, has been designed to demonstrate that&#xD;
        the regular intake of an OA-enriched functional olive oil is effective as an adjuvant to&#xD;
        metformin antidiabetic drug therapy. The hypothesis is that the inclusion of this functional&#xD;
        olive oil in the diet will enhance the effects of the pharmacological treatment in diabetic&#xD;
        patients, and may even reduce the need for prescription of such medications.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        TRIAL DESIGN The OLTRAD Study is a prospective, parallel group, randomized, double-blind,&#xD;
        controlled trial designed to demonstrate that the regular intake of an OA-enriched functional&#xD;
        olive oil is effective as an adjunct to metformin therapy (as monotherapy or in combination&#xD;
        with other antidiabetic drugs) in the metabolic control of T2DM patients. The effect of the&#xD;
        OA-enriched olive oil will be compared with that of the control oil, which consists of the&#xD;
        same commercial olive oil not fortified in the triterpene.&#xD;
  &#xD;
        A total of 100 volunteers of both sex will be selected from among the T2DM patients treated&#xD;
        at the Endocrinology and Nutrition Service of the 'Virgen del Rocío' University Hospital&#xD;
        (Seville, SPAIN).&#xD;
  &#xD;
        SAMPLE SIZE CALCULATION Serum glycosylated hemoglobin (HbA1c) is adopted as the main&#xD;
        quantitative variable for the analysis of glycemic control. The null hypothesis stated in the&#xD;
        trial design is that the OA-based dietary intervention will reduce the baseline serum HbA1c&#xD;
        levels of patients by at least 7%, compared to the control group. To test this one-sided&#xD;
        hypothesis test with a 95% confidence level (α risk = 0.05) and 95% power (β risk = 0.05), a&#xD;
        sample size of 44 volunteers per group is required. However, due to the characteristics of&#xD;
        the study (a long-term lifestyle intervention), participant losses of up to 15% can be&#xD;
        assumed, resulting in an adjusted sample size of 50 individuals per group.&#xD;
  &#xD;
        RANDOMIZATION Once recruited, the 100 T2DM patients will be randomly assigned to one of the&#xD;
        two study groups. Fifty individuals will be assigned to the intervention group, which will&#xD;
        ingest the OA-enriched functional olive oil, whereas the other 50 volunteers will be assigned&#xD;
        to the control group, which will receive the same non-enriched olive oil. At the time of&#xD;
        admission, the study nursing staff will request by telephone the clinical coordinator of the&#xD;
        trial (Principal Investigator 2 of the Project) the assignment of participants to the study&#xD;
        groups (centralized randomization). Allocation to these groups will be made using computer&#xD;
        generated tables of random numbers. Four randomization strata will be constructed by sex and&#xD;
        age (cuttof 50 years).&#xD;
  &#xD;
        INTERVENTION Participants will be instructed to ingest 55 mL/day of the assigned oil,&#xD;
        preferably raw and freely distributed among the three main meals. Both the OA-enriched olive&#xD;
        oil and the control oil will be delivered labeled with alphanumeric codes, the correspondence&#xD;
        of which will only be known by the Principal Investigator 1 of the project. This ensures&#xD;
        blinding of the clinical researchers and participants with respect to the type of olive oil&#xD;
        assigned.&#xD;
  &#xD;
        FOLLOW-UP Participants in the clinical trial will be followed up for 12 months from&#xD;
        enrollment, according to a plan of quarterly visits.&#xD;
  &#xD;
        At the time of recruitment and every three months thereafter, participants will be measured&#xD;
        for anthropometric, blood pressure, and heart rate measurements. They will also be asked&#xD;
        about gastrointestinal disorders or other types of complaints, and will complete a&#xD;
        questionnaire on lifestyle (diet, physical activity, alcohol and tobacco use), medical&#xD;
        conditions, and medication use.&#xD;
  &#xD;
        Also at the beginning of participation in the study and every three months thereafter,&#xD;
        fasting blood samples will be drawn from the cubital vein, which will be collected in sterile&#xD;
        plastic tubes with a vacuum system. Similarly, participants will provide aliquots of their&#xD;
        first morning urine in sterile plastic tubes. The analytical determinations in blood and&#xD;
        urine will be carried out in the Clinical Biochemistry and Analysis Laboratory of the 'Virgen&#xD;
        del Rocío' University Hospital in Seville (HUVR).&#xD;
  &#xD;
        In addition, aliquots of plasma will be sent to the 'Instituto de la Grasa' (IG-CSIC) for&#xD;
        complementary biochemical determinations. Laboratory technicians from both institutions will&#xD;
        receive the samples identified with alphanumeric ID codes and, therefore, will be blinded to&#xD;
        the intervention groups.&#xD;
  &#xD;
        In these quarterly visits, volunteers will participate in sessions of the nutritional&#xD;
        education program and will receive 6 L of the assigned oil for free. Adherence to the dietary&#xD;
        intervention will be assessed quarterly through the Haynes-Sackett's self-reported compliance&#xD;
        test and the return of empty bottles presumably consumed.&#xD;
  &#xD;
        The primary outcome of the trial is the improvement in glycemic control, assessed by the&#xD;
        evolution of HbA1c. As secondary results, we will obtain data on anthropometric and clinical&#xD;
        variables, as well as on biochemical parameters of blood and urine.&#xD;
  &#xD;
        ANAMNESIS AND CLINICAL EXAMINATION OF PARTICIPANTS The medical researchers of the project&#xD;
        have access to the electronic medical records of the participants in the platform DIRAYA of&#xD;
        the Andalusian Health Service, and will carry out the anamnesis and physical examination of&#xD;
        the participants, which will include vital data and general medical and surgical history, as&#xD;
        well as the pharmacological treatments followed. Information will also be obtained on&#xD;
        lifestyle, perception of their own body image, diet, and the type and intensity of physical&#xD;
        activity. In addition, a general clinical examination will be carried out including general&#xD;
        appearance and inspection of hands and arms, feet and legs, skin, face, eyes, mouth, neck,&#xD;
        abdomen, edema, lymph nodes, and vital signs (temperature, pulse, respiratory rate and blood&#xD;
        pressure).&#xD;
  &#xD;
        ANTHROPOMETRIC STUDY AND BODY COMPOSITION The anthropometric study will include the&#xD;
        determination of total body weight, height, body mass index (BMI), as well as waist and hip&#xD;
        circumferences. The study and evaluation of these variables will be carried out according to&#xD;
        the guidelines of the International Society for the Advancement of Kinanthropometry (ISAK).&#xD;
        The study of body composition will be carried out by electrical bioimpedance. Fat mass, lean&#xD;
        mass, muscle mass, total water, bone mass, basal metabolism, and visceral fat will be&#xD;
        quantified with this technique, using validated prediction equations adjusted for age and&#xD;
        sex.&#xD;
  &#xD;
        ASSESSMENT OF FOOD INTAKE AND NUTRITIONAL TRAINING A nutritional education program will be&#xD;
        implemented to assess the food intake of the participants and reinforce compliance with the&#xD;
        dietary recommendations given. To measure food intake, we will use the food intake&#xD;
        registration form designed by the University of Navarra (Spain) and used successfully in&#xD;
        other trials, such as the PREvención con DIeta MEDiterránea (PREDIMED) study. This form is a&#xD;
        validated tool that quantifies food intake in terms of food portions or food groups for&#xD;
        adults living in Spain. On the other hand, all the participants will join workshops where&#xD;
        they will receive specific dietary recommendations for patients with T2DM, and they will be&#xD;
        instructed on a healthy diet, the best food options and adequate portions, limiting highly&#xD;
        processed foods, cakes, sugar, fatty foods as well as sugary and alcoholic beverages.&#xD;
        Additionally, patients will gain information on recipes, seasonal shopping lists, and the use&#xD;
        of olive oil for cooking and dressing. The eating habits of the participants will be analyzed&#xD;
        quarterly by means of a 24-hour recall questionnaire. The 'NUTRIUM' software&#xD;
        (https://nutrium.com/; Braga; Portugal) for the nutritional evaluation of the diets will be&#xD;
        used.&#xD;
  &#xD;
        BLOOD BIOCHEMISTRY IN HUVR In ulnar blood samples, determinations related to circulating&#xD;
        lipids [total triglycerides, total cholesterol, LDL, HDL, total apolipoprotein B and&#xD;
        lipoprotein A]; glucose homeostasis [glycemia, insulinemia, C-peptide, HOMA-IR index, HbA1c];&#xD;
        oxidative stress and inflammation [uric acid, bilirubin, malondialdehyde, ultrasensitive&#xD;
        C-reactive protein, thyroid-stimulating hormone (TSH)], as well as those associated with&#xD;
        liver and kidney damage [lactate dehydrogenase (LDH), liver transaminases (ALT, AST, GGT )&#xD;
        and creatinine] will be performed.&#xD;
  &#xD;
        Plasma level of vitamin B12 will be also assessed. In addition, the possible appearance of&#xD;
        liver fibrosis will be evaluated through the Hepamet Fibrosis Score, a non-invasive method&#xD;
        that calculates a score taking into account factors such as age, sex, presence of diabetes,&#xD;
        glucose levels, insulin, albumin, platelets, and AST. This tool, designed by the Seville&#xD;
        Institute of Biomedicine (IBiS), is indicated to assess suspected fibrosis in patients with&#xD;
        obesity, diabetes, metabolic syndrome, hepatic steatosis, and/or abnormal liver function&#xD;
        markers. The method offers diagnostic reliability and a cost/benefit ratio that is superior&#xD;
        to other methods, such as the FIB-4 and the NAFLD Fibrosis Score.&#xD;
  &#xD;
        CONTINUOUS BLOOD GLUCOSE MONITORING Plasma glucose will be continuously monitored using the&#xD;
        'FreeStyle Libre' subcutaneous system (ABBOTT Diagnostics; Chicago, IL.; USA). The sensors&#xD;
        will be attached to the participants at two times throughout the trial: at baseline and after&#xD;
        12 months of follow-up, and will collect data for 48 hours. With this system, different&#xD;
        glycemic parameters will be determined, such as the area under the curve (AUC), the mean&#xD;
        amplitude of the glycemic excursion (MAGE), the mean glycemia, as well as the standard&#xD;
        deviation (SD) and the coefficient of variation (CV).&#xD;
  &#xD;
        PLASMA BIOCHEMISTRY IN IG-CSIC The investigators of the IG-CSIC will perform a number of&#xD;
        complementary determinations in plasma samples, such as the plasmatic concentrations of OA,&#xD;
        the glutathione (GSH and GSSG) levels, the fatty acid composition, serum adipokines&#xD;
        (ceruloplasmin, adiponectin, leptin, resistin, and ghrelin). Serum Antioxidant enzymes&#xD;
        (superoxide dismutase, catalase) and proinflammatory cytokines (TNF-α, IL-1β, IL-6) will also&#xD;
        be determined.&#xD;
  &#xD;
        On the other hand, the VLDL fraction of plasma lipoproteins will be isolated by&#xD;
        ultracentrifugation (230,000 × g for 18 h at 4 °C). In these particles, the total content of&#xD;
        fatty acids, triglycerides, diglycerides, phospholipids and total Apolipoprotein B will be&#xD;
        measured.&#xD;
  &#xD;
        URINE ANALYSIS The first morning urine samples will be analyzed for the usual physical,&#xD;
        chemical, and microscopic determinations (pH, density, glycosuria, ketones, nitrites,&#xD;
        urobilinogen, bilirubin, sediment, leukocytes, microalbuminuria/g creatinine). The&#xD;
        determination of these parameters will also be carried out in the facilities of the Clinical&#xD;
        Biochemistry and Analysis Laboratory of the 'Virgen del Rocío' University Hospitals in&#xD;
        Seville.&#xD;
  &#xD;
        STATISTICAL ANALYSIS The trial will be conducted according to the intention-to-treat (ITT)&#xD;
        principle. Qualitative variables will be expressed by their absolute and relative&#xD;
        frequencies, whereas the quantitative ones with normal distribution will be expressed by the&#xD;
        mean and standard deviation and those with non-normal distribution by the median and&#xD;
        interquartile range (IQR). Comparisons between study groups for qualitative variables will be&#xD;
        performed with the Chi-square and McNemar's tests, whereas comparisons for quantitative&#xD;
        variables will be executed with the Student's t-test and ANOVA. The homogeneity of the&#xD;
        populations included in the allocation groups will be evaluated using&#xD;
        theMann-Whitney-Wilcoxon U-test. All P-values will be two-tailed at α = 0.05. Statistical&#xD;
        analysis will be performed with SPSS 27 (IBM SPSS Statistics, NY, USA) software&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">February 25, 2022</start_date>
    <completion_date type="Anticipated">June 30, 2025</completion_date>
    <primary_completion_date type="Anticipated">December 30, 2024</primary_completion_date>
    <phase>Phase 2</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <intervention_model_description>prospective, parallel group, randomized, double-blind, controlled trial</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
      <masking_description>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.</masking_description>
    </study_design_info>
    <primary_outcome>
      <measure>HbA1c</measure>
      <time_frame>1 year</time_frame>
      <description>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 %</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Body weight</measure>
      <time_frame>1 year</time_frame>
      <description>Body weight (expressed in kilograms, kg) wil be determined using a TANITA® model BC-418MA body composition analyzer.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Body height</measure>
      <time_frame>1 year</time_frame>
      <description>The body height (expressed in meters, m) will be determined by using an approved column stadiometer</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Body mass index (BMI)</measure>
      <time_frame>1 year</time_frame>
      <description>body weight and height will be combined to report BMI in kg/m^2, according to the equation BMI = body mass/(height)^2</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Waist circumference</measure>
      <time_frame>1 year</time_frame>
      <description>Waist circumference (expressed in centimeters, cm) will be measured with a measuring tape</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Hip circumference</measure>
      <time_frame>1 year</time_frame>
      <description>Hip circumference (expressed in centimeters, cm) will be measured with a measuring tape</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Body composition - fat mass</measure>
      <time_frame>1 year</time_frame>
      <description>Fat mass (expressed in kilograms, kg) will be measured using a TANITA® (model BC-418MA) body composition analyzer. Quantification will be made using validated prediction equations adjusted for age and sex.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Body composition - visceral fat mass</measure>
      <time_frame>1 year</time_frame>
      <description>Visceral fat mass (expressed in kilograms, kg) will be measured using a TANITA® (model BC-418MA) body composition analyzer. Quantification will be made using validated prediction equations adjusted for age and sex.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Body composition - lean mass</measure>
      <time_frame>1 year</time_frame>
      <description>Lean mass (expressed in kilograms, kg) will be measured using a TANITA® (model BC-418MA) body composition analyzer. Quantification will be made using validated prediction equations adjusted for age and sex.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Body composition - muscle mass</measure>
      <time_frame>1 year</time_frame>
      <description>Muscle mass (expressed in kilograms, kg) will be measured using a TANITA® (model BC-418MA) body composition analyzer. Quantification will be made using validated prediction equations adjusted for age and sex.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Body composition - bone mass</measure>
      <time_frame>1 year</time_frame>
      <description>Bone mass (expressed in kilograms, kg) will be measured using a TANITA® (model BC-418MA) body composition analyzer. Quantification will be made using validated prediction equations adjusted for age and sex.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Body composition - total water composition</measure>
      <time_frame>1 year</time_frame>
      <description>Total water composition (expressed in litre, L) will be measured using a TANITA® (model BC-418MA) body composition analyzer. Quantification will be made using validated prediction equations adjusted for age and sex.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Basal metabolism</measure>
      <time_frame>1 year</time_frame>
      <description>Basal metabolism (expressed in kilojoule, kJ) will be measured using a TANITA® (model BC-418MA) body composition analyzer. Quantification will be made using validated prediction equations adjusted for age and sex.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Diastolic blood pressure (DBP)</measure>
      <time_frame>1 year</time_frame>
      <description>DBP (expressed in milimeters of mercury) using a calibrated automatic sphygmomanometer</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Systolic blood pressure (SBP)</measure>
      <time_frame>1 year</time_frame>
      <description>SBP (expressed in milimeters of mercury) using a calibrated automatic sphygmomanometer</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Pulse</measure>
      <time_frame>1 year</time_frame>
      <description>heart rate measured with a calibrated automatic sphygmomanometer</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Serum glucose</measure>
      <time_frame>1 year</time_frame>
      <description>Determined by enzymatic method and expressed in miligrams/decilitre (mg/dL)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Serum insulin</measure>
      <time_frame>1 year</time_frame>
      <description>determined by commercial ELISA kit and expressed in international microunits per millilitre (µIU/mL)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>HOMA-IR index</measure>
      <time_frame>1 year</time_frame>
      <description>serum glucose (expressed in millimole/litre) and serum insulin (expressed in µIU/mL) are combined to report the homeostatic model assessment for insulin resistance (HOMA-IR), according to the equation HOMA-IR = (glucose x insulin)/22.5 HOMA-IR= [serum insulin (μU/ml) × blood glucose (mmol/l)]/22.5}.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Serum C-peptide</measure>
      <time_frame>1 year</time_frame>
      <description>measured by commercial ELISA kit and expressed as nanogram/millilitre (ng/mL)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Plasma triglycerides (TG)</measure>
      <time_frame>1 year</time_frame>
      <description>plasma concentrations of total triglycerides is determined by an automated colorimetric enzymatic method (GPO-PAP, Roche Diagnostics, Mannheim, Germany) and expressed as milligrams/decilitre (mg/dL)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Plasma total cholesterol (CT)</measure>
      <time_frame>1 year</time_frame>
      <description>plasma concentrations of total cholesterol is determined by an automated colorimetric enzymatic method (CHOD-PAP, Roche Diagnostics, Mannheim, Germany) and expressed as milligrams/decilitre (mg/dL)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Plasma high density lipoproteins (HDL)</measure>
      <time_frame>1 year</time_frame>
      <description>plasma concentrations of HDL is determined by an automated direct enzymatic method (HDL-C-plus 2nd generation, Roche Diagnostics, Mannheim, Germany) and expressed as milligrams/decilitre (mg/dL)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Plasma low density lipoproteins (LDL)</measure>
      <time_frame>1 year</time_frame>
      <description>Triglycerides, total cholesterol and high densitity lipoproteins are combined to report LDL, according to the Friedewald formula:&#xD;
  LDL = CT - (TG/ 5) - HDL</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Plasma lipoprotein A</measure>
      <time_frame>1 year</time_frame>
      <description>the plasma content of lipoprotein A is quantified by ELISA and the values are expressed as milligram/decilitre (mg/dL)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Plasma total lipoprotein B</measure>
      <time_frame>1 year</time_frame>
      <description>the plasma content of total lipoprotein B (Apo B48 + Apo B100) is quantified by an immunoturbidimetric assay (Tinaquant; Roche Diagnostics, Mannheim, Germany), The values are expressed as milligram/decilitre (mg/dL)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Plasma creatinine</measure>
      <time_frame>1 year</time_frame>
      <description>standard spectrophotometric assay. Values expressed as milligrams per decilitre (mg/dL)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Plasma uric acid</measure>
      <time_frame>1 year</time_frame>
      <description>Evaluated by an enzymatic procedure, with results expressed in milligrams per decilitre (mg/dL)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Plasma alanine aminotransferase (ALT)</measure>
      <time_frame>1 year</time_frame>
      <description>use of a diagnose kit with values expressed as units per litre (U/L)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Plasma aspartate aminotransferase (AST)</measure>
      <time_frame>1 year</time_frame>
      <description>use of a diagnose kit with values expressed as units per litre (U/L)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Plasma gamma-glutamyl transferase (GGT)</measure>
      <time_frame>1 year</time_frame>
      <description>use of a diagnose kit with values expressed as units per litre (U/L)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Plasma lactate dehydrogenase (LDH)</measure>
      <time_frame>1 year</time_frame>
      <description>L-Lactic Dehydrogenase kit. Results expressed as units per litre (U/L)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Plasma bilirubin</measure>
      <time_frame>1 year</time_frame>
      <description>Spectrofotometric assay. Results expressed as milligrams per decilitre (mg/dL)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Plasma levels of glutathion (GSH and GSSG)</measure>
      <time_frame>1 year</time_frame>
      <description>Glutathione Reductase (GR) Assay Kit. Values expressed as milliunits per millilitre (mU/mL)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Plasma malondialdehyde</measure>
      <time_frame>1 year</time_frame>
      <description>Thiobarbituric acid (TBA) assay and HPLC determination. Results expressed as µmole per litre (µmol/L)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Plasma ultra-sensitive C-reactive protein</measure>
      <time_frame>1 year</time_frame>
      <description>Immunoturbidimetric method. Results expressed as milligrams per litre (mg/L)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Plasma vitamin B12</measure>
      <time_frame>1 year</time_frame>
      <description>chemiluminescence immunoassay (CLIA). Results expressed as picograms per millilitre (pg/mL)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Plasma thyroid-stimulating hormone (TSH)</measure>
      <time_frame>1 year</time_frame>
      <description>ELISA kit. Values expressed as international micro-units per millilitre (µlU/ml)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Plasma levels of Oleanolic acid</measure>
      <time_frame>1 year</time_frame>
      <description>Liquid/liquid extraction and quantification by gas chromatography con flame ionization detection (GC-FID). Values expressed as nanograms per millilitre (ng/mL)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Serum fatty acids composition</measure>
      <time_frame>1 year</time_frame>
      <description>Liquid/liquid extraction and quantification by gas chromatography con flame ionization detection (GC-FID). Values expressed as percentage of the total of fatty acids (%)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Plasma adiponectin</measure>
      <time_frame>1 year</time_frame>
      <description>ELISA kit. values expressed as picograms per millilitre (pg/mL)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Plasma ceruloplasmin</measure>
      <time_frame>1 year</time_frame>
      <description>ELISA kit. values expressed as milligrams per decilitre (mg/dL)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Plasma leptin</measure>
      <time_frame>1 year (measures at the time of recruitment and every three months thereafter)</time_frame>
      <description>ELISA kit. values expressed as picograms per millilitre (pg/mL)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Plasma resistin</measure>
      <time_frame>1 year</time_frame>
      <description>ELISA kit. values expressed as picograms per millilitre (pg/mL)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Plasma ghrelin</measure>
      <time_frame>1 year</time_frame>
      <description>ELISA kit. values expressed as picograms per millilitre (pg/mL)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Plasma catalase</measure>
      <time_frame>1 year</time_frame>
      <description>ELISA kit. values expressed as micromole per milligrams of protein (µmol/mg protein)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Plasma superoxide dismutase</measure>
      <time_frame>1 year</time_frame>
      <description>ELISA kit. values expressed as units per millilitre (U/mL)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Plasma tumor necrosis factor-alpha (TNF-alpha)</measure>
      <time_frame>1 year</time_frame>
      <description>ELISA kit. values expressed as picograms per millilitre (pg/mL)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Plasma interleukine 1-beta</measure>
      <time_frame>1 year</time_frame>
      <description>ELISA kit. values expressed as picograms per millilitre (pg/mL)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Plasma interleukine 6</measure>
      <time_frame>1 year</time_frame>
      <description>ELISA kit. values expressed as picograms per millilitre (pg/mL)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Triglycerides in VLDL</measure>
      <time_frame>1 year</time_frame>
      <description>the VLDL fraction of plasma lipoproteins will be isolated by ultracentrifugation (230,000 × g for 18 h at 4 0C). Lipds will be extracted by a modification of the Folch's method. Triglycerides are determined by HPLC, and results expressed as milligrams per milligram of protein (mg/mg protein)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Diglycerides in VLDL</measure>
      <time_frame>1 year</time_frame>
      <description>the VLDL fraction of plasma lipoproteins will be isolated by ultracentrifugation (230,000 × g for 18 h at 4 0C). Lipds will be extracted by a modification of the Folch's method. Diglycerides are determined by HPLC, and results expressed as milligrams per milligram of protein (mg/mg protein)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Phospholipids in VLDL</measure>
      <time_frame>1 year</time_frame>
      <description>the VLDL fraction of plasma lipoproteins will be isolated by ultracentrifugation (230,000 × g for 18 h at 4 0C). Lipds will be extracted by a modification of the Folch's method. Phospholipids are determined by HPLC, and results expressed as milligrams per milligram of protein (mg/mg protein)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Fatty acids composition of VLDL</measure>
      <time_frame>1 year</time_frame>
      <description>the VLDL fraction of plasma lipoproteins will be isolated by ultracentrifugation (230,000 × g for 18 h at 4 0C). Lipds will be extracted by a modification of the Folch's method. Fatty acids are derivatized to their methyl esters and analyzed by gas chromatography. The results are expressed as percentage of the total of fatty acids (%)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Apo B in VLDL</measure>
      <time_frame>1 year</time_frame>
      <description>Determined by immunoturbidimetry using a commercial kit. Values expressed as micrograms per milligram of protein (µg/mg protein)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Continuous blood glucose monitoring</measure>
      <time_frame>1 year</time_frame>
      <description>FreeStyle Libre subcutaneous system (ABBOTT Diagnostics). Values expressed as milligrams per decilitre (mg/dL)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Blood Count - hematocrit</measure>
      <time_frame>1 year</time_frame>
      <description>Automated blood analyzer. Results expressed as percentage (%)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Blood Count - red blood cells</measure>
      <time_frame>1 year</time_frame>
      <description>Automated blood analyzer. Results expressed as cell count x 10^6 per microlitre (count x 10^6/µL)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Blood Count - hemoglobin</measure>
      <time_frame>1 year</time_frame>
      <description>Automated blood analyzer. Results expressed as gram per decilitre (g/dL)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Blood Count - mean corpuscular volume</measure>
      <time_frame>1 year</time_frame>
      <description>Automated blood analyzer. Results expressed as femtolitre (fL)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Blood Count - mean corpuscular hemoglobin</measure>
      <time_frame>1 year</time_frame>
      <description>Automated blood analyzer. Results expressed as picograms (pg)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Blood Count - leukocytes</measure>
      <time_frame>1 year</time_frame>
      <description>Automated blood analyzer. Results expressed as count x 10^3 per microlitre (count x 10^3 /µL)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Blood Count - neutrophils</measure>
      <time_frame>1 year</time_frame>
      <description>Automated blood analyzer. Results expressed as count x 10^3 per microlitre (count x 10^3 /µL)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Blood Count - lymphocytes</measure>
      <time_frame>1 year</time_frame>
      <description>Automated blood analyzer. Results expressed as count x 10^3 per microlitre (count x 10^3 /µL)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Blood Count - monocytes</measure>
      <time_frame>1 year</time_frame>
      <description>Automated blood analyzer. Results expressed as count x 10^3 per microlitre (count x 10^3 /µL)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Blood Count - eosinophils</measure>
      <time_frame>1 year</time_frame>
      <description>Automated blood analyzer. Results expressed as count x 10^3 per microlitre (count x 10^3 /µL)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Blood Count - basophils</measure>
      <time_frame>1 year</time_frame>
      <description>Automated blood analyzer. Results expressed as count x 10^3 per microlitre (count x 10^3 /µL)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Blood Count - platelets</measure>
      <time_frame>1 year</time_frame>
      <description>Automated blood analyzer. Results expressed as count x 10^3 per microlitre (count x 10^3 /µL)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Blood Count - partial thromboplastin time</measure>
      <time_frame>1 year</time_frame>
      <description>Automated blood analyzer. Results expressed as seconds (s)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Blood Count - prothrombin time</measure>
      <time_frame>1 year</time_frame>
      <description>Automated blood analyzer. Results expressed as seconds (s)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Blood Count - coagulative fibrinogen</measure>
      <time_frame>1 year</time_frame>
      <description>Automated blood analyzer. Results expressed as milligrams per decilitre (mg/dL)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Urine pH</measure>
      <time_frame>1 year</time_frame>
      <description>Urine pH</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Urine density</measure>
      <time_frame>1 year</time_frame>
      <description>Automated urine analyzer. Results expressed as milligrams per millilitre (mg/mL)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Glycosuria</measure>
      <time_frame>1 year</time_frame>
      <description>Automated urine analyzer. Results expressed as milligrams per decilitre (mg/dL)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Ketone bodies in urine</measure>
      <time_frame>1 year</time_frame>
      <description>Automated urine analyzer. Results expressed as millimole per litre (mmol/L)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Presence of nitrite in urine</measure>
      <time_frame>1 year</time_frame>
      <description>Automated urine analyzer. Results expressed as negative or positive</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Urobilinogen</measure>
      <time_frame>1 year</time_frame>
      <description>Automated urine analyzer. Results expressed as milligrams per decilitre (mg/dL)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Urine bilirubin</measure>
      <time_frame>1 year</time_frame>
      <description>Automated urine analyzer. Results expressed as milligrams per decilitre (mg/dL)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Urine creatinine</measure>
      <time_frame>1 year</time_frame>
      <description>Automated urine analyzer. Results expressed as milligrams per decilitre (mg/dL)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Urine albumin/creatinine ratio (UACR)</measure>
      <time_frame>1 year</time_frame>
      <description>Automated urine analyzer. Results expressed as milligrams of albumin per gram of creatinine</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Leukocytes in urine</measure>
      <time_frame>1 year</time_frame>
      <description>Automated urine analyzer. Results expressed as count x 1 per microlitre (count x 1 /µL)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Presence of sediment in urine</measure>
      <time_frame>1 year</time_frame>
      <description>Automated urine analyzer. Results expressed as negative or positive</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">100</enrollment>
    <condition>Diabetic Patients</condition>
    <condition>Type II Diabetes Mellitus</condition>
    <arm_group>
      <arm_group_label>OA-enriched functional olive oil</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Functional olive oil elaborated enriching the control olive oil with high purity (&gt; 95 %) Oleanolic acid from olive leaf up to 600 mg OA/kg oil.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Control olive oil</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Commercial olive oil (blend of virgin and refined olive oils) chosen by its very low content of bioactive minor components.</description>
    </arm_group>
    <intervention>
      <intervention_type>Dietary Supplement</intervention_type>
      <intervention_name>OA-enriched functional olive oil</intervention_name>
      <description>Dietary intervention in diabetic patients. Oral intake of 55 mL/day of a functional olive oil enriched in Oleanolic acid (equivalent dose 30 mg/day OA) Oleanolic acid (CAS no. 598-02-1; PubChem CID 10494).</description>
      <arm_group_label>OA-enriched functional olive oil</arm_group_label>
      <other_name>Functional olive oil enriched in Oleanolic acid</other_name>
    </intervention>
    <intervention>
      <intervention_type>Dietary Supplement</intervention_type>
      <intervention_name>commercial olive oil</intervention_name>
      <description>Dietary intervention in diabetic patients. Oral intake of 55 mL/day of a commercial olive oil (blend of virgin and refined olive oils) chosen by its very low content of bioactive minor components.</description>
      <arm_group_label>Control olive oil</arm_group_label>
      <other_name>control olive oil</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. community-residing men and women aged.&#xD;
  &#xD;
            2. Body Mass Index (BMI) between 25 and 39.9 kg/m2.&#xD;
  &#xD;
            3. diagnosed with T2DM [Following the American Diabetes Association (ADA) 2019 criteria]&#xD;
               at least six months before being included in this trial.&#xD;
  &#xD;
            4. be treated with metformin (stable dose &gt;= 850 mg/day at least three months before&#xD;
               recruitment) as monotherapy, or in combination with other hypoglycemic agents&#xD;
               (administration of insulin exclusively in a single basal dose), except pioglitazone&#xD;
               and sulphonylureas.&#xD;
  &#xD;
            5. HbA1c below 9% at baseline, with a variation compared with a prior HbA1c from at least&#xD;
               three months before inclusion in this trial of less than +/- 0.5 %.&#xD;
  &#xD;
            6. be able to give voluntary informed consent and willing to comply with all study&#xD;
               procedures.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. suffering from Type 1 Diabetes Mellitus or latent autoimmune diabetes in adults.&#xD;
  &#xD;
            2. suffering from chronic kidney disease (estimated glomerular filtration rate (eGFR) &lt;30&#xD;
               ml/min/1.73m2).&#xD;
  &#xD;
            3. suffering from acute or chronic hepatitis, signs and symptoms of any liver disease&#xD;
               other than non-alcoholic fatty liver disease (NAFLD), or ALT/AST ratio &gt;3 times the&#xD;
               upper limit of the reference range.&#xD;
  &#xD;
            4. To present, at the time of recruitment, allergies and intolerances associated with&#xD;
               food consumption.&#xD;
  &#xD;
            5. pregnant and lactating women.&#xD;
  &#xD;
            6. lack of willingness to use a highly effective contraceptive method (in women of&#xD;
               childbearing potential).&#xD;
  &#xD;
            7. fasting triglyceridemia &gt; 600 mg/dL despite adequate treatment.&#xD;
  &#xD;
            8. grade 3 hypertension (systolic blood pressure ≥ 180 mm Hg and/or diastolic blood&#xD;
               pressure ≥ 110 mm Hg) according to the 2018 guidelines of the European Society of&#xD;
               Hypertension.&#xD;
  &#xD;
            9. use of pioglitazone or sulfonylureas.&#xD;
  &#xD;
           10. being treated with medications that promote weight loss (eg, Saxenda® [liraglutide 3.0&#xD;
               mg], Xenical® [orlistat], or similar over-the-counter [OTC] medications) within six&#xD;
               months prior to the start of the trial.&#xD;
  &#xD;
           11. Being on chronic (&gt;14 days) therapy with systemic glucocorticoids (excluding topical,&#xD;
               intraocular, intranasal, intra-articular, or inhaled preparations) within six months&#xD;
               prior to enrollment.&#xD;
  &#xD;
           12. Presenting any of the following cardiovascular conditions within 6 months prior to&#xD;
               study entry: acute myocardial infarction, unstable angina, New York Heart Association&#xD;
               (NYHA) class III or class IV heart failure, or cerebrovascular accident.&#xD;
  &#xD;
           13. Evidence, in the investigators' opinion, of significant uncontrolled endocrine&#xD;
               abnormality (e.g., thyrotoxicosis, adrenal crisis) at baseline.&#xD;
  &#xD;
           14. History of active or untreated malignancy, or being in remission from a clinically&#xD;
               significant malignancy (other than basal or squamous cell skin cancer, cervical&#xD;
               carcinoma in situ, or prostate cancer in situ) during the last 5 years before the&#xD;
               study entry.&#xD;
  &#xD;
           15. Participation in the last 30 days in a clinical trial with an investigational product&#xD;
               [if the previous investigational product has a long half-life, 3 months or 5&#xD;
               half-lives (whichever is longer) should have passed].&#xD;
  &#xD;
           16. Being, at the time of recruitment, enrolled in any other clinical trial involving an&#xD;
               investigational product or any other type of medical research that is not considered&#xD;
               scientifically or medically compatible with this study.&#xD;
  &#xD;
           17. Presence of any hematologic condition that may interfere with HbA1c measurement (eg,&#xD;
               hemolytic anemias, sickle cell anemia).&#xD;
  &#xD;
           18. History of any other condition (eg, known drug or alcohol abuse or psychiatric&#xD;
               disorder, or any other physical or intellectual limitations), which, in the opinion of&#xD;
               the investigator, may prevent the patient from following and completing the protocols.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>75 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>José María Castellano, PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Spanish National Research Council (CSIC)</affiliation>
    </overall_official>
    <overall_official>
      <last_name>Pedro Pablo García-Luna, MD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Virgen del Rocío University Hospital</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Pedro Pablo García-Luna, MD</last_name>
      <phone>+34 955013551</phone>
      <email>garcialunapp@yahoo.es</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>José María Castellano, PhD</last_name>
      <phone>+34 954611550</phone>
      <phone_ext>431088</phone_ext>
      <email>jmcas@ig.csic.es</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Virgen del Rocío University Hospital</name>
        <address>
          <city>Sevilla</city>
          <state>Andalicía</state>
          <zip>41013</zip>
          <country>Spain</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Pedro Pablo García-Luna, MD</last_name>
        <phone>+34 955013551</phone>
        <email>garcialunapp@yahoo.es</email>
      </contact>
    </location>
    <location_countries>
      <country>Spain</country>
    </location_countries>
    <link>
      <url>https://estudiooltrad.wixsite.com/oltrad</url>
      <description>website of the OLTRAD Project (BIO-OLTRAD and OLTRAD trials</description>
    </link>
    <reference>
      <citation>Castellano JM, Ramos-Romero S, Perona JS. Oleanolic Acid: Extraction, Characterization and Biological Activity. Nutrients. 2022 Jan 31;14(3):623. doi: 10.3390/nu14030623.</citation>
      <PMID>35276982</PMID>
    </reference>
    <reference>
      <citation>Fernandez-Aparicio A, Schmidt-RioValle J, Perona JS, Correa-Rodriguez M, Castellano JM, Gonzalez-Jimenez E. Potential Protective Effect of Oleanolic Acid on the Components of Metabolic Syndrome: A Systematic Review. J Clin Med. 2019 Aug 23;8(9):1294. doi: 10.3390/jcm8091294.</citation>
      <PMID>31450844</PMID>
    </reference>
    <reference>
      <citation>Castellano JM, Guinda A, Delgado T, Rada M, Cayuela JA. Biochemical basis of the antidiabetic activity of oleanolic acid and related pentacyclic triterpenes. Diabetes. 2013 Jun;62(6):1791-9. doi: 10.2337/db12-1215.</citation>
      <PMID>23704520</PMID>
    </reference>
    <reference>
      <citation>Santos-Lozano JM, Rada M, Lapetra J, Guinda A, Jimenez-Rodriguez MC, Cayuela JA, Angel-Lugo A, Vilches-Arenas A, Gomez-Martin AM, Ortega-Calvo M, Castellano JM. Prevention of type 2 diabetes in prediabetic patients by using functional olive oil enriched in oleanolic acid: The PREDIABOLE study, a randomized controlled trial. Diabetes Obes Metab. 2019 Nov;21(11):2526-2534. doi: 10.1111/dom.13838. Epub 2019 Aug 28.</citation>
      <PMID>31364228</PMID>
    </reference>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>July 24, 2023</study_first_submitted>
    <study_first_submitted_qc>September 1, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 11, 2023</study_first_posted>
    <last_update_submitted>September 1, 2023</last_update_submitted>
    <last_update_submitted_qc>September 1, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 11, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Spanish National Research Council</investigator_affiliation>
      <investigator_full_name>José M. Castellano, PhD</investigator_full_name>
      <investigator_title>Principal Investigator</investigator_title>
    </responsible_party>
    <keyword>Oleanolic acid</keyword>
    <keyword>T2DM treatment</keyword>
    <keyword>randomized controlled trial</keyword>
    <keyword>parallel groups design</keyword>
    <keyword>dietary intervention</keyword>
    <keyword>functional olive oil</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Diabetes Mellitus</mesh_term>
      <mesh_term>Diabetes Mellitus, Type 2</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: download date: ClinicalTrials.gov processed this data on September 20, 2023
  link text: Link to the current ClinicalTrials.gov record.
  url: https://clinicaltrials.gov/ct2/show/NCT06030544
  org study id: PID2019-107837RB-I00
  nct id: NCT06030544
  lead sponsor: 
  collaborator: 
  collaborator: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  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.
  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.
  
        FOLLOW-UP Participants in the clinical trial will be followed up for 12 months from
        enrollment, according to a plan of quarterly visits.
  
        At the time of recruitment and every three months thereafter, participants will be measured
        for anthropometric, blood pressure, and heart rate measurements. They will also be asked
        about gastrointestinal disorders or other types of complaints, and will complete a
        questionnaire on lifestyle (diet, physical activity, alcohol and tobacco use), medical
        conditions, and medication use.
  
        Also at the beginning of participation in the study and every three months thereafter,
        fasting blood samples will be drawn from the cubital vein, which will be collected in sterile
        plastic tubes with a vacuum system. Similarly, participants will provide aliquots of their
        first morning urine in sterile plastic tubes. The analytical determinations in blood and
        urine will be carried out in the Clinical Biochemistry and Analysis Laboratory of the 'Virgen
        del Rocío' University Hospital in Seville (HUVR).
  
        In addition, aliquots of plasma will be sent to the 'Instituto de la Grasa' (IG-CSIC) for
        complementary biochemical determinations. Laboratory technicians from both institutions will
        receive the samples identified with alphanumeric ID codes and, therefore, will be blinded to
        the intervention groups.
  
        In these quarterly visits, volunteers will participate in sessions of the nutritional
        education program and will receive 6 L of the assigned oil for free. Adherence to the dietary
        intervention will be assessed quarterly through the Haynes-Sackett's self-reported compliance
        test and the return of empty bottles presumably consumed.
  
        The primary outcome of the trial is the improvement in glycemic control, assessed by the
        evolution of HbA1c. As secondary results, we will obtain data on anthropometric and clinical
        variables, as well as on biochemical parameters of blood and urine.
  
        ANAMNESIS AND CLINICAL EXAMINATION OF PARTICIPANTS The medical researchers of the project
        have access to the electronic medical records of the participants in the platform DIRAYA of
        the Andalusian Health Service, and will carry out the anamnesis and physical examination of
        the participants, which will include vital data and general medical and surgical history, as
        well as the pharmacological treatments followed. Information will also be obtained on
        lifestyle, perception of their own body image, diet, and the type and intensity of physical
        activity. In addition, a general clinical examination will be carried out including general
        appearance and inspection of hands and arms, feet and legs, skin, face, eyes, mouth, neck,
        abdomen, edema, lymph nodes, and vital signs (temperature, pulse, respiratory rate and blood
        pressure).
  
        ANTHROPOMETRIC STUDY AND BODY COMPOSITION The anthropometric study will include the
        determination of total body weight, height, body mass index (BMI), as well as waist and hip
        circumferences. The study and evaluation of these variables will be carried out according to
        the guidelines of the International Society for the Advancement of Kinanthropometry (ISAK).
        The study of body composition will be carried out by electrical bioimpedance. Fat mass, lean
        mass, muscle mass, total water, bone mass, basal metabolism, and visceral fat will be
        quantified with this technique, using validated prediction equations adjusted for age and
        sex.
  
        ASSESSMENT OF FOOD INTAKE AND NUTRITIONAL TRAINING A nutritional education program will be
        implemented to assess the food intake of the participants and reinforce compliance with the
        dietary recommendations given. To measure food intake, we will use the food intake
        registration form designed by the University of Navarra (Spain) and used successfully in
        other trials, such as the PREvención con DIeta MEDiterránea (PREDIMED) study. This form is a
        validated tool that quantifies food intake in terms of food portions or food groups for
        adults living in Spain. On the other hand, all the participants will join workshops where
        they will receive specific dietary recommendations for patients with T2DM, and they will be
        instructed on a healthy diet, the best food options and adequate portions, limiting highly
        processed foods, cakes, sugar, fatty foods as well as sugary and alcoholic beverages.
        Additionally, patients will gain information on recipes, seasonal shopping lists, and the use
        of olive oil for cooking and dressing. The eating habits of the participants will be analyzed
        quarterly by means of a 24-hour recall questionnaire. The 'NUTRIUM' software
        (https://nutrium.com/; Braga; Portugal) for the nutritional evaluation of the diets will be
        used.
  
        BLOOD BIOCHEMISTRY IN HUVR In ulnar blood samples, determinations related to circulating
        lipids [total triglycerides, total cholesterol, LDL, HDL, total apolipoprotein B and
        lipoprotein A]; glucose homeostasis [glycemia, insulinemia, C-peptide, HOMA-IR index, HbA1c];
        oxidative stress and inflammation [uric acid, bilirubin, malondialdehyde, ultrasensitive
        C-reactive protein, thyroid-stimulating hormone (TSH)], as well as those associated with
        liver and kidney damage [lactate dehydrogenase (LDH), liver transaminases (ALT, AST, GGT )
        and creatinine] will be performed.
  
        Plasma level of vitamin B12 will be also assessed. In addition, the possible appearance of
        liver fibrosis will be evaluated through the Hepamet Fibrosis Score, a non-invasive method
        that calculates a score taking into account factors such as age, sex, presence of diabetes,
        glucose levels, insulin, albumin, platelets, and AST. This tool, designed by the Seville
        Institute of Biomedicine (IBiS), is indicated to assess suspected fibrosis in patients with
        obesity, diabetes, metabolic syndrome, hepatic steatosis, and/or abnormal liver function
        markers. The method offers diagnostic reliability and a cost/benefit ratio that is superior
        to other methods, such as the FIB-4 and the NAFLD Fibrosis Score.
  
        CONTINUOUS BLOOD GLUCOSE MONITORING Plasma glucose will be continuously monitored using the
        'FreeStyle Libre' subcutaneous system (ABBOTT Diagnostics; Chicago, IL.; USA). The sensors
        will be attached to the participants at two times throughout the trial: at baseline and after
        12 months of follow-up, and will collect data for 48 hours. With this system, different
        glycemic parameters will be determined, such as the area under the curve (AUC), the mean
        amplitude of the glycemic excursion (MAGE), the mean glycemia, as well as the standard
        deviation (SD) and the coefficient of variation (CV).
  
        PLASMA BIOCHEMISTRY IN IG-CSIC The investigators of the IG-CSIC will perform a number of
        complementary determinations in plasma samples, such as the plasmatic concentrations of OA,
        the glutathione (GSH and GSSG) levels, the fatty acid composition, serum adipokines
        (ceruloplasmin, adiponectin, leptin, resistin, and ghrelin). Serum Antioxidant enzymes
        (superoxide dismutase, catalase) and proinflammatory cytokines (TNF-α, IL-1β, IL-6) will also
        be determined.
  
        On the other hand, the VLDL fraction of plasma lipoproteins will be isolated by
        ultracentrifugation (230,000 × g for 18 h at 4 °C). In these particles, the total content of
        fatty acids, triglycerides, diglycerides, phospholipids and total Apolipoprotein B will be
        measured.
  
        URINE ANALYSIS The first morning urine samples will be analyzed for the usual physical,
        chemical, and microscopic determinations (pH, density, glycosuria, ketones, nitrites,
        urobilinogen, bilirubin, sediment, leukocytes, microalbuminuria/g creatinine). The
        determination of these parameters will also be carried out in the facilities of the Clinical
        Biochemistry and Analysis Laboratory of the 'Virgen del Rocío' University Hospitals in
        Seville.
  
        STATISTICAL ANALYSIS The trial will be conducted according to the intention-to-treat (ITT)
        principle. Qualitative variables will be expressed by their absolute and relative
        frequencies, whereas the quantitative ones with normal distribution will be expressed by the
        mean and standard deviation and those with non-normal distribution by the median and
        interquartile range (IQR). Comparisons between study groups for qualitative variables will be
        performed with the Chi-square and McNemar's tests, whereas comparisons for quantitative
        variables will be executed with the Student's t-test and ANOVA. The homogeneity of the
        populations included in the allocation groups will be evaluated using
        theMann-Whitney-Wilcoxon U-test. All P-values will be two-tailed at α = 0.05. Statistical
        analysis will be performed with SPSS 27 (IBM SPSS Statistics, NY, USA) software
  allocation: Randomized
  intervention model: Parallel Assignment
  intervention model description: prospective, parallel group, randomized, double-blind, controlled trial
  primary purpose: Treatment
  masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  masking description: 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.
  measure: HbA1c
  time frame: 1 year
  description: 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 %
  measure: Body weight
  time frame: 1 year
  description: Body weight (expressed in kilograms, kg) wil be determined using a TANITA® model BC-418MA body composition analyzer.
  measure: Body height
  time frame: 1 year
  description: The body height (expressed in meters, m) will be determined by using an approved column stadiometer
  measure: Body mass index (BMI)
  time frame: 1 year
  description: body weight and height will be combined to report BMI in kg/m^2, according to the equation BMI = body mass/(height)^2
  measure: Waist circumference
  time frame: 1 year
  description: Waist circumference (expressed in centimeters, cm) will be measured with a measuring tape
  measure: Hip circumference
  time frame: 1 year
  description: Hip circumference (expressed in centimeters, cm) will be measured with a measuring tape
  measure: Body composition - fat mass
  time frame: 1 year
  description: Fat mass (expressed in kilograms, kg) will be measured using a TANITA® (model BC-418MA) body composition analyzer. Quantification will be made using validated prediction equations adjusted for age and sex.
  measure: Body composition - visceral fat mass
  time frame: 1 year
  description: Visceral fat mass (expressed in kilograms, kg) will be measured using a TANITA® (model BC-418MA) body composition analyzer. Quantification will be made using validated prediction equations adjusted for age and sex.
  measure: Body composition - lean mass
  time frame: 1 year
  description: Lean mass (expressed in kilograms, kg) will be measured using a TANITA® (model BC-418MA) body composition analyzer. Quantification will be made using validated prediction equations adjusted for age and sex.
  measure: Body composition - muscle mass
  time frame: 1 year
  description: Muscle mass (expressed in kilograms, kg) will be measured using a TANITA® (model BC-418MA) body composition analyzer. Quantification will be made using validated prediction equations adjusted for age and sex.
  measure: Body composition - bone mass
  time frame: 1 year
  description: Bone mass (expressed in kilograms, kg) will be measured using a TANITA® (model BC-418MA) body composition analyzer. Quantification will be made using validated prediction equations adjusted for age and sex.
  measure: Body composition - total water composition
  time frame: 1 year
  description: Total water composition (expressed in litre, L) will be measured using a TANITA® (model BC-418MA) body composition analyzer. Quantification will be made using validated prediction equations adjusted for age and sex.
  measure: Basal metabolism
  time frame: 1 year
  description: Basal metabolism (expressed in kilojoule, kJ) will be measured using a TANITA® (model BC-418MA) body composition analyzer. Quantification will be made using validated prediction equations adjusted for age and sex.
  measure: Diastolic blood pressure (DBP)
  time frame: 1 year
  description: DBP (expressed in milimeters of mercury) using a calibrated automatic sphygmomanometer
  measure: Systolic blood pressure (SBP)
  time frame: 1 year
  description: SBP (expressed in milimeters of mercury) using a calibrated automatic sphygmomanometer
  measure: Pulse
  time frame: 1 year
  description: heart rate measured with a calibrated automatic sphygmomanometer
  measure: Serum glucose
  time frame: 1 year
  description: Determined by enzymatic method and expressed in miligrams/decilitre (mg/dL)
  measure: Serum insulin
  time frame: 1 year
  description: determined by commercial ELISA kit and expressed in international microunits per millilitre (µIU/mL)
  measure: HOMA-IR index
  time frame: 1 year
  description: serum glucose (expressed in millimole/litre) and serum insulin (expressed in µIU/mL) are combined to report the homeostatic model assessment for insulin resistance (HOMA-IR), according to the equation HOMA-IR = (glucose x insulin)/22.5 HOMA-IR= [serum insulin (μU/ml) × blood glucose (mmol/l)]/22.5}.
  measure: Serum C-peptide
  time frame: 1 year
  description: measured by commercial ELISA kit and expressed as nanogram/millilitre (ng/mL)
  measure: Plasma triglycerides (TG)
  time frame: 1 year
  description: plasma concentrations of total triglycerides is determined by an automated colorimetric enzymatic method (GPO-PAP, Roche Diagnostics, Mannheim, Germany) and expressed as milligrams/decilitre (mg/dL)
  measure: Plasma total cholesterol (CT)
  time frame: 1 year
  description: plasma concentrations of total cholesterol is determined by an automated colorimetric enzymatic method (CHOD-PAP, Roche Diagnostics, Mannheim, Germany) and expressed as milligrams/decilitre (mg/dL)
  measure: Plasma high density lipoproteins (HDL)
  time frame: 1 year
  description: plasma concentrations of HDL is determined by an automated direct enzymatic method (HDL-C-plus 2nd generation, Roche Diagnostics, Mannheim, Germany) and expressed as milligrams/decilitre (mg/dL)
  measure: Plasma low density lipoproteins (LDL)
  time frame: 1 year
  description: Triglycerides, total cholesterol and high densitity lipoproteins are combined to report LDL, according to the Friedewald formula:
  LDL = CT - (TG/ 5) - HDL
  measure: Plasma lipoprotein A
  time frame: 1 year
  description: the plasma content of lipoprotein A is quantified by ELISA and the values are expressed as milligram/decilitre (mg/dL)
  measure: Plasma total lipoprotein B
  time frame: 1 year
  description: the plasma content of total lipoprotein B (Apo B48 + Apo B100) is quantified by an immunoturbidimetric assay (Tinaquant; Roche Diagnostics, Mannheim, Germany), The values are expressed as milligram/decilitre (mg/dL)
  measure: Plasma creatinine
  time frame: 1 year
  description: standard spectrophotometric assay. Values expressed as milligrams per decilitre (mg/dL)
  measure: Plasma uric acid
  time frame: 1 year
  description: Evaluated by an enzymatic procedure, with results expressed in milligrams per decilitre (mg/dL)
  measure: Plasma alanine aminotransferase (ALT)
  time frame: 1 year
  description: use of a diagnose kit with values expressed as units per litre (U/L)
  measure: Plasma aspartate aminotransferase (AST)
  time frame: 1 year
  description: use of a diagnose kit with values expressed as units per litre (U/L)
  measure: Plasma gamma-glutamyl transferase (GGT)
  time frame: 1 year
  description: use of a diagnose kit with values expressed as units per litre (U/L)
  measure: Plasma lactate dehydrogenase (LDH)
  time frame: 1 year
  description: L-Lactic Dehydrogenase kit. Results expressed as units per litre (U/L)
  measure: Plasma bilirubin
  time frame: 1 year
  description: Spectrofotometric assay. Results expressed as milligrams per decilitre (mg/dL)
  measure: Plasma levels of glutathion (GSH and GSSG)
  time frame: 1 year
  description: Glutathione Reductase (GR) Assay Kit. Values expressed as milliunits per millilitre (mU/mL)
  measure: Plasma malondialdehyde
  time frame: 1 year
  description: Thiobarbituric acid (TBA) assay and HPLC determination. Results expressed as µmole per litre (µmol/L)
  measure: Plasma ultra-sensitive C-reactive protein
  time frame: 1 year
  description: Immunoturbidimetric method. Results expressed as milligrams per litre (mg/L)
  measure: Plasma vitamin B12
  time frame: 1 year
  description: chemiluminescence immunoassay (CLIA). Results expressed as picograms per millilitre (pg/mL)
  measure: Plasma thyroid-stimulating hormone (TSH)
  time frame: 1 year
  description: ELISA kit. Values expressed as international micro-units per millilitre (µlU/ml)
  measure: Plasma levels of Oleanolic acid
  time frame: 1 year
  description: Liquid/liquid extraction and quantification by gas chromatography con flame ionization detection (GC-FID). Values expressed as nanograms per millilitre (ng/mL)
  measure: Serum fatty acids composition
  time frame: 1 year
  description: Liquid/liquid extraction and quantification by gas chromatography con flame ionization detection (GC-FID). Values expressed as percentage of the total of fatty acids (%)
  measure: Plasma adiponectin
  time frame: 1 year
  description: ELISA kit. values expressed as picograms per millilitre (pg/mL)
  measure: Plasma ceruloplasmin
  time frame: 1 year
  description: ELISA kit. values expressed as milligrams per decilitre (mg/dL)
  measure: Plasma leptin
  time frame: 1 year (measures at the time of recruitment and every three months thereafter)
  description: ELISA kit. values expressed as picograms per millilitre (pg/mL)
  measure: Plasma resistin
  time frame: 1 year
  description: ELISA kit. values expressed as picograms per millilitre (pg/mL)
  measure: Plasma ghrelin
  time frame: 1 year
  description: ELISA kit. values expressed as picograms per millilitre (pg/mL)
  measure: Plasma catalase
  time frame: 1 year
  description: ELISA kit. values expressed as micromole per milligrams of protein (µmol/mg protein)
  measure: Plasma superoxide dismutase
  time frame: 1 year
  description: ELISA kit. values expressed as units per millilitre (U/mL)
  measure: Plasma tumor necrosis factor-alpha (TNF-alpha)
  time frame: 1 year
  description: ELISA kit. values expressed as picograms per millilitre (pg/mL)
  measure: Plasma interleukine 1-beta
  time frame: 1 year
  description: ELISA kit. values expressed as picograms per millilitre (pg/mL)
  measure: Plasma interleukine 6
  time frame: 1 year
  description: ELISA kit. values expressed as picograms per millilitre (pg/mL)
  measure: Triglycerides in VLDL
  time frame: 1 year
  description: the VLDL fraction of plasma lipoproteins will be isolated by ultracentrifugation (230,000 × g for 18 h at 4 0C). Lipds will be extracted by a modification of the Folch's method. Triglycerides are determined by HPLC, and results expressed as milligrams per milligram of protein (mg/mg protein)
  measure: Diglycerides in VLDL
  time frame: 1 year
  description: the VLDL fraction of plasma lipoproteins will be isolated by ultracentrifugation (230,000 × g for 18 h at 4 0C). Lipds will be extracted by a modification of the Folch's method. Diglycerides are determined by HPLC, and results expressed as milligrams per milligram of protein (mg/mg protein)
  measure: Phospholipids in VLDL
  time frame: 1 year
  description: the VLDL fraction of plasma lipoproteins will be isolated by ultracentrifugation (230,000 × g for 18 h at 4 0C). Lipds will be extracted by a modification of the Folch's method. Phospholipids are determined by HPLC, and results expressed as milligrams per milligram of protein (mg/mg protein)
  measure: Fatty acids composition of VLDL
  time frame: 1 year
  description: the VLDL fraction of plasma lipoproteins will be isolated by ultracentrifugation (230,000 × g for 18 h at 4 0C). Lipds will be extracted by a modification of the Folch's method. Fatty acids are derivatized to their methyl esters and analyzed by gas chromatography. The results are expressed as percentage of the total of fatty acids (%)
  measure: Apo B in VLDL
  time frame: 1 year
  description: Determined by immunoturbidimetry using a commercial kit. Values expressed as micrograms per milligram of protein (µg/mg protein)
  measure: Continuous blood glucose monitoring
  time frame: 1 year
  description: FreeStyle Libre subcutaneous system (ABBOTT Diagnostics). Values expressed as milligrams per decilitre (mg/dL)
  measure: Blood Count - hematocrit
  time frame: 1 year
  description: Automated blood analyzer. Results expressed as percentage (%)
  measure: Blood Count - red blood cells
  time frame: 1 year
  description: Automated blood analyzer. Results expressed as cell count x 10^6 per microlitre (count x 10^6/µL)
  measure: Blood Count - hemoglobin
  time frame: 1 year
  description: Automated blood analyzer. Results expressed as gram per decilitre (g/dL)
  measure: Blood Count - mean corpuscular volume
  time frame: 1 year
  description: Automated blood analyzer. Results expressed as femtolitre (fL)
  measure: Blood Count - mean corpuscular hemoglobin
  time frame: 1 year
  description: Automated blood analyzer. Results expressed as picograms (pg)
  measure: Blood Count - leukocytes
  time frame: 1 year
  description: Automated blood analyzer. Results expressed as count x 10^3 per microlitre (count x 10^3 /µL)
  measure: Blood Count - neutrophils
  time frame: 1 year
  description: Automated blood analyzer. Results expressed as count x 10^3 per microlitre (count x 10^3 /µL)
  measure: Blood Count - lymphocytes
  time frame: 1 year
  description: Automated blood analyzer. Results expressed as count x 10^3 per microlitre (count x 10^3 /µL)
  measure: Blood Count - monocytes
  time frame: 1 year
  description: Automated blood analyzer. Results expressed as count x 10^3 per microlitre (count x 10^3 /µL)
  measure: Blood Count - eosinophils
  time frame: 1 year
  description: Automated blood analyzer. Results expressed as count x 10^3 per microlitre (count x 10^3 /µL)
  measure: Blood Count - basophils
  time frame: 1 year
  description: Automated blood analyzer. Results expressed as count x 10^3 per microlitre (count x 10^3 /µL)
  measure: Blood Count - platelets
  time frame: 1 year
  description: Automated blood analyzer. Results expressed as count x 10^3 per microlitre (count x 10^3 /µL)
  measure: Blood Count - partial thromboplastin time
  time frame: 1 year
  description: Automated blood analyzer. Results expressed as seconds (s)
  measure: Blood Count - prothrombin time
  time frame: 1 year
  description: Automated blood analyzer. Results expressed as seconds (s)
  measure: Blood Count - coagulative fibrinogen
  time frame: 1 year
  description: Automated blood analyzer. Results expressed as milligrams per decilitre (mg/dL)
  measure: Urine pH
  time frame: 1 year
  description: Urine pH
  measure: Urine density
  time frame: 1 year
  description: Automated urine analyzer. Results expressed as milligrams per millilitre (mg/mL)
  measure: Glycosuria
  time frame: 1 year
  description: Automated urine analyzer. Results expressed as milligrams per decilitre (mg/dL)
  measure: Ketone bodies in urine
  time frame: 1 year
  description: Automated urine analyzer. Results expressed as millimole per litre (mmol/L)
  measure: Presence of nitrite in urine
  time frame: 1 year
  description: Automated urine analyzer. Results expressed as negative or positive
  measure: Urobilinogen
  time frame: 1 year
  description: Automated urine analyzer. Results expressed as milligrams per decilitre (mg/dL)
  measure: Urine bilirubin
  time frame: 1 year
  description: Automated urine analyzer. Results expressed as milligrams per decilitre (mg/dL)
  measure: Urine creatinine
  time frame: 1 year
  description: Automated urine analyzer. Results expressed as milligrams per decilitre (mg/dL)
  measure: Urine albumin/creatinine ratio (UACR)
  time frame: 1 year
  description: Automated urine analyzer. Results expressed as milligrams of albumin per gram of creatinine
  measure: Leukocytes in urine
  time frame: 1 year
  description: Automated urine analyzer. Results expressed as count x 1 per microlitre (count x 1 /µL)
  measure: Presence of sediment in urine
  time frame: 1 year
  description: Automated urine analyzer. Results expressed as negative or positive
  arm group label: OA-enriched functional olive oil
  arm group type: Experimental
  description: Functional olive oil elaborated enriching the control olive oil with high purity (> 95 %) Oleanolic acid from olive leaf up to 600 mg OA/kg oil.
  arm group label: Control olive oil
  arm group type: Active Comparator
  description: Commercial olive oil (blend of virgin and refined olive oils) chosen by its very low content of bioactive minor components.
  intervention type: Dietary Supplement
  intervention name: OA-enriched functional olive oil
  description: Dietary intervention in diabetic patients. Oral intake of 55 mL/day of a functional olive oil enriched in Oleanolic acid (equivalent dose 30 mg/day OA) Oleanolic acid (CAS no. 598-02-1; PubChem CID 10494).
  arm group label: OA-enriched functional olive oil
  other name: Functional olive oil enriched in Oleanolic acid
  intervention type: Dietary Supplement
  intervention name: commercial olive oil
  description: Dietary intervention in diabetic patients. Oral intake of 55 mL/day of a commercial olive oil (blend of virgin and refined olive oils) chosen by its very low content of bioactive minor components.
  arm group label: Control olive oil
  other name: control olive oil
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 75 Years
  healthy volunteers: No
  last name: José María Castellano, PhD
  role: Principal Investigator
  affiliation: Spanish National Research Council (CSIC)
  last name: Pedro Pablo García-Luna, MD
  role: Principal Investigator
  affiliation: Virgen del Rocío University Hospital
  last name: Pedro Pablo García-Luna, MD
  phone: +34 955013551
  email: garcialunapp@yahoo.es
  last name: José María Castellano, PhD
  phone: +34 954611550
  phone ext: 431088
  email: jmcas@ig.csic.es
  facility: 
  status: Recruiting
  contact: 
  country: Spain
  url: https://estudiooltrad.wixsite.com/oltrad
  description: website of the OLTRAD Project (BIO-OLTRAD and OLTRAD trials
  citation: Castellano JM, Ramos-Romero S, Perona JS. Oleanolic Acid: Extraction, Characterization and Biological Activity. Nutrients. 2022 Jan 31;14(3):623. doi: 10.3390/nu14030623.
  PMID: 35276982
  citation: Fernandez-Aparicio A, Schmidt-RioValle J, Perona JS, Correa-Rodriguez M, Castellano JM, Gonzalez-Jimenez E. Potential Protective Effect of Oleanolic Acid on the Components of Metabolic Syndrome: A Systematic Review. J Clin Med. 2019 Aug 23;8(9):1294. doi: 10.3390/jcm8091294.
  PMID: 31450844
  citation: Castellano JM, Guinda A, Delgado T, Rada M, Cayuela JA. Biochemical basis of the antidiabetic activity of oleanolic acid and related pentacyclic triterpenes. Diabetes. 2013 Jun;62(6):1791-9. doi: 10.2337/db12-1215.
  PMID: 23704520
  citation: Santos-Lozano JM, Rada M, Lapetra J, Guinda A, Jimenez-Rodriguez MC, Cayuela JA, Angel-Lugo A, Vilches-Arenas A, Gomez-Martin AM, Ortega-Calvo M, Castellano JM. Prevention of type 2 diabetes in prediabetic patients by using functional olive oil enriched in oleanolic acid: The PREDIABOLE study, a randomized controlled trial. Diabetes Obes Metab. 2019 Nov;21(11):2526-2534. doi: 10.1111/dom.13838. Epub 2019 Aug 28.
  PMID: 31364228
  responsible party type: Principal Investigator
  investigator affiliation: Spanish National Research Council
  investigator full name: José M. Castellano, PhD
  investigator title: Principal Investigator
  mesh term: Diabetes Mellitus
  mesh term: Diabetes Mellitus, Type 2
  sharing ipd: No