Antidiabetic Effect of Olive Pomace Oil (OPODIABE)

Assessment of the Potential Antidiabetic Effects of Olive Pomace Oil in Diabetic or Prediabetic Subjects: Postprandial Study and Chronic Intervention

This clinical trial aims at assessing whether consumption of olive pomace oil in the diet may benefit persons with type 2 diabetes mellitus or persons at risk of developing the disease (prediabetic persons).

The main questions the study aims to answer are:

• May olive pomace oil prevent a high increase of blood glucose levels when consumed in a meal together with carbohydrates in diabetic/prediabetic patients?
• May olive pomace oil decrease fasting blood glucose levels of diabetic/prediabetic patients after consuming it daily?
• May daily consumption of olive pomace oil improve glucose homeostasis and other alterations like elevated blood lipids or inflammation, which also affect persons with diabetes or prediabetes?

Researchers will compare the effect of consuming olive pomace oil to the effects of a comparison oil (high-oleic acid sunflower oil).

Participants will:

In different days, they will consume white bread alone or the oils (olive pomace oil, high-oleic acid sunflower oil or extra virgin olive oil) spread on white bread and blood will be collected at different times during 2 h. This study to observe the increase of blood glucose after a carbohydrate-rich breakfast will be part of the so-called "postprandial" study, and will be conducted during 3 weeks, during which participants will consume corn oil on a daily basis.

Participants will also take part in the "chronic" study, that will last 22 weeks in total. During this study, they will firstly "wash" the effects of the oil they normally consume in their diets by consuming corn oil during 3 weeks. It is during these weeks when they will attend the Human Nutrition Unit (HNU) of ICTAN to carry on the "postprandial" study described in the previous paragraph.

After the initial 3 weeks, participants will consume olive pomace oil as the only oil in their diets during 8 weeks, "wash" its effects again by consuming corn oil during 3 weeks and then change to consume the other oil (high-oleic acid sunflower oil) during 8 weeks.

During the chronic study, they will visit the clinic once every 4 weeks for checkups and tests. They will refrain from eating other oils or specific fat-rich foods. Participants will also attend our phone calls to ask them what they ate the day before on different weeks during the study, and wear an accelerometer during 1 week to record their physical activity. They will keep a diary of the doses of insulin/metformin used and the blood glucose levels they measured at home.

Study Overview

• Status: Recruiting
• Conditions: Diabetes Mellitus; Diabetes; Type 2 Diabetes Mellitus; Prediabetic State; Prediabetes (Insulin Resistance, Impaired Glucose Tolerance)
• Intervention / Treatment: Dietary supplement: Experimental arm: Olive pomace oil; Dietary supplement: High-oleic acid sunflower oil

Detailed Description

This trial comprises 2 studies in parallel, a postprandial study and a chronic intervention.

In the postprandial study, participants will attend the Human Nutrition Unit (HNU) of ICTAN in different days. During these visits, they will consume white bread (50 g) alone or with 10 g of extra virgin olive oil (EVOO), olive pomace oil (OPO) or high-oleic acid sunflower oil (HOSO). A nurse will insert a catheter in the non-prevailing arm and collect fasting blood (0 h) and blood samples 1 and 2 h after consuming the bread/oil to measure the postprandial glycemic/insulinemic response, as well as incretins (GLP-1, GIP). Blood lipids will also be determined. These visits will be carried out during the 3-week run-in period prior to the chronic intervention, when the EVOO and control (white bread) tests will be carried out (weeks 1 and 2, respectively). Then, coinciding with the first day of the chronic intervention, participants will consume either OPO or HOSO as corresponding to the randomized allocation to each oil. The other postprandial test will be carried out at the beginning of the second intervention after crossover and wash-out, thus avoiding additional visits and discomfort to the participants.

The chronic study is a crossover, randomized, blind, clinical trial. After a 3-week run-in during which participants will consume corn oil as the only dietary oil, they will be randomly allocated to one of each intervention arms, OPO or HOSO, each lasting 8 weeks. Then, a 3-week wash-out period with corn oil will follow before changing to consuming the other oil.

During the study, participants should avoid other oils and fats such as olives, sunflower seeds, butter, margarine, nuts or avocados.

During the chronic intervention, participants will visit the HNU at the beginning (week 1), middle (week 4) and at the end (week 8) of each intervention arm. A nurse will collect a fasting blood sample and measure blood pressure. An analysis of body weight and body composition (anthropometric and bioimpedance measurements) will be performed. Participants should maintain their habitual diet and exercise level throughout the study; diet will be monitored by periodic 24-h recall questionnaires (a trained member of the team will phone participants on 3 different days (including a festive one) before each visit to the HNU to enquire what they ate the previous day). In addition, a physical activity questionnaire will be completed at the beginning of the study and, on each intervention arm, participants will carry during 7 days an accelerometer to monitor real physical activity.

Biochemical, hormonal and inflammatory markers will be measured in blood samples to assess the potential effect of olive pomace oil on different outcomes of relevance in the management of blood glucose in diabetic/prediabetic persons, including glucose homeostasis, insulin resistance, blood lipid levels, liver function, different hormones, incretins, adipokines, pro- and anti-inflammatory cytokines, on integrity of the intestinal barrier.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Laura Bravo, Professor; Phone Number: 436350 +34 91 5492300; Email: lbravo@ictan.csic.es
• Study Contact Backup: Name: Beatriz Sarria, Dr; Phone Number: 436342 +34 91 5492300; Email: beasarria@ictan.csic.es

Study Locations

• Spain
  • Madrid, Spain, 28040
    • Recruiting
    • Institute of Food Science, Technology and Nutrition (ICTAN-CSIC)
    • Contact: Laura Bravo, Professor; Phone Number: 436350 +34 91 5492300; Email: lbravo@ictan.csic.es
    • Contact: Beatriz Sarria, Dr; Phone Number: 436342 +34 91 5492300; Email: beasarria@ictan.csic.es
    • Contact: Álvaro Fernandez-Cardero, MSc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Fasting blood glucose between 100-126 mg/dL and/or
• Glycated haemoglobin (HbA1c) between 5.7-6.4% and/or
• Diabetic persons with Fasting blood glucose >126 mg/dL and/or
• Diabetic persons with Glycated haemoglobin (HbA1c) > 6.4%

Exclusion Criteria:

• Kidney or liver diseases
• Gastrointestinal diseases (irritable bowel syndrome, Crohn disease, chronic bowel inflammation)
• Food allergies/intolerances
• Vegetarians/vegans
• Smoking
• Pregnant or lactating women
• On prescription drugs other than for hypertension/thyroid/dyslipidemia/glucose control, or changes in dosage in the last 3 months
• Consumption of vitamins, dietary supplements or nutraceuticals

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Olive pomace oil; Consumption of olive pomace oil as the only dietary fat.	Dietary supplement: Experimental arm: Olive pomace oil; Participants will consume during 8 weeks either the test oil (olive pomace oil) as the only dietary fat. They will consume 45 g/day of oil, using it in salads, fried foods, as spread on toasts, etc.
Active Comparator: High-sunflower olive oil; Consumption of high-oleic acid sunflower oil as the only dietary fat.	Dietary supplement: High-oleic acid sunflower oil; Participants will consume during 8 weeks either the test active comparator oil (high-oleic acid sunflower oil) as the only dietary fat. They will consume 45 g/day of oil, using it in salads, fried foods, as spread on toasts, etc.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fasting blood glucose	Change of fasting blood glucose levels at the end of the chronic intervention	From enrollment to the end of each treatment at 8 weeks
Postprandial blood glucose response	Change of postprandial blood glucose levels after consuming white bread with oil in comparison with white bread only. Blood will be collected at 0 h and 1 and 2 h after consuming the bread alone or with the corresponding oil. Olive pomace oil (active comparator) and high-oleic acid sunflower oil (active comparator) will be tested. Only in this postprandial study extra virgin olive oil will also be tested as a positive control (at the beginning of the run-in), along with white bread only (at week 2 of the run-in). Test/comparator oils will be assessed at the beginning of each arm, week 1 of each intervention arm (corresponding to weeks 4 and 14 of the study).	From enrollment until week 14 of the study

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Insulin levels	Change in fasting blood insulin levels at the end of the chronic intervention	From enrollment to the end of each treatment at 8 weeks
Insulin resistance	Change in homeostasis model assessment (HOMA) of insulin resistance (HOMA-IR) at the end of the chronic intervention	From enrollment to the end of each treatment at 8 weeks
Glycated hemoglobin	Change in blood levels of glycated hemoglobin (HbA1c) at the end of the chronic intervention	From enrollment to the end of each treatment at 8 weeks
Beta-cell function	Change in homeostasis model assessment (HOMA) of beta-cell function (HOMA-B) at the end of the chronic intervention	From enrollment to the end of each treatment at 8 weeks
Insulin sensitivity	Change in quantitative insulin levels sensitivity check index (QUICKI) at the end of the chronic intervention. Higher score in QUICKI means a better outcome compared to initial values.	From enrollment to the end of each treatment at 8 weeks
Postprandial insulin response	Change of postprandial blood insulin levels after consuming white bread with oil in comparison with white bread only. Blood will be collected at 0 h and 1 and 2 h after consuming the bread alone or with the corresponding oil. Olive pomace oil (active comparator) and high-oleic acid sunflower oil (active comparator) will be tested. Only in this postprandial study extra virgin olive oil will also be tested as a positive control (at the beginning of the run-in), along with white bread only (at week 2 of the run-in). Test/comparator oils will be assessed at the beginning of each arm, week 1 of each intervention arm (corresponding to weeks 4 and 14 of the study).	From enrollment to week 14 of the study
Postprandial incretins	Change of postprandial levels of GLP-1 and GIP after consuming white bread with oil in comparison with white bread only. Blood will be collected at 0 h and 1 and 2 h after consuming the bread alone or with the corresponding oil. Olive pomace oil (active comparator) and high-oleic acid sunflower oil (active comparator) will be tested. Only in this postprandial study extra virgin olive oil will also be tested as a positive control (at the beginning of the run-in), along with white bread only (at week 2 of the run-in). Test/comparator oils will be assessed at the beginning of each arm, week 1 of each intervention arm (corresponding to weeks 4 and 14 of the study).	From enrollment to week 14 of the study
Postprandial blood lipids	Change of postprandial blood lipid levels after consuming white bread with oil in comparison with white bread only. Blood will be collected at 0 h and 1 and 2 h after consuming the bread alone or with the corresponding oil. Olive pomace oil (active comparator) and high-oleic acid sunflower oil (active comparator) will be tested. Only in this postprandial study extra virgin olive oil will also be tested as a positive control (at the beginning of the run-in), along with white bread only (at week 2 of the run-in). Test/comparator oils will be assessed at the beginning of each arm, week 1 of each intervention arm (corresponding to weeks 4 and 14 of the study).	From enrollment to week 14 of the study

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood lipids	Change in serum levels of total cholesterol or LDL-cholesterol or HDL-cholesterol or triglycerides or apolipoprotein A1 or apolipoprotein B at the end of the chronic intervention	From enrollment to the end of each treatment at 8 weeks
Inflammatory cytokines	Change in the levels of C-reactive protein (CRP), or pro-inflammatory cytokines (tumor necrosis factor-alpha (TNF-a), or interferon gamma (IFN-g), or interleukin (IL)-1beta (IL-1b), or IL-2, or IL-5, or IL-6, or IL-7, or IL-8, or IL-13)) or anti-inflammatory cytokines IL-4 or IL-10 at the end of the chronic intervention	From enrollment to the end of each treatment at 8 weeks
Intestinal barrier function	Changes in blood levels of lipopolysaccharide (LPS) or zonulin at the end of the chronic intervention	From enrollment to the end of each treatment at 8 weeks
Liver function	No changes in serum levels of alanine transferase (ALAT), or aspartate transferase (ASAT) or gamma-glutamyl transferase (GGT) at the end of the chronic intervention	From enrollment to the end of each treatment at 8 weeks
Hormones, incretins and adipokines levels	Changes in serum levels of C peptide or glucagon or fibroblast growth factor 21 (FGF21) or glucagon inhibitory peptide (GIP) or glucagon-like peptide type 1 (GLP-1) or ghrelin or leptin or resistin or plasminogen activator inhibitor type 1 (PAI-1) or visfatin or adiponectin or adipsin or dipeptidyl peptidase IV (DPP IV) at the end of the chronic intervention	From enrollment to the end of each treatment at 8 weeks

Collaborators and Investigators

• Sponsor: Instituto de Ciencia y Tecnología de Alimentos y Nutrición
• Collaborators: ICTAN-CSIC - Madrid - Spain
• Investigators: Principal Investigator: Laura Bravo, Professor, ICTAN-CSIC

Study record dates

Study Major Dates

• Study Start (Estimated): January 15, 2025
• Primary Completion (Estimated): March 30, 2026
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: December 4, 2024
• First Submitted That Met QC Criteria: December 6, 2024
• First Posted (Actual): December 9, 2024

Study Record Updates

• Last Update Posted (Estimated): December 11, 2024
• Last Update Submitted That Met QC Criteria: December 6, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: Diabetes; Prediabetes; Olive pomace oil; Antidiabetic effect; Postprandial study; Chronic intervention; High-oleic acid sunflower oil
• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Glucose Metabolism Disorders; Hyperinsulinism; Hyperglycemia; Diabetes Mellitus, Type 2; Diabetes Mellitus; Insulin Resistance; Prediabetic State; Glucose Intolerance
• Other Study ID Numbers: 20232949; 253405 (Other Identifier: CSIC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Interesting researchers may contact the principal investigator
• IPD Sharing Time Frame: After completion of the study and publication of results
• IPD Sharing Access Criteria: Justified request to the principal investigator
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No