Oleanolic Acid as Therapeutic Adjuvant for Type 2 Diabetes Mellitus (OLTRAD STUDY)

NCT06030544 | Active Not Recruiting Phase 2

• 1 other identifier: PID2019-107837RB-I00
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Diabetic Patients; Type II Diabetes Mellitus

Keywords

Oleanolic acid; T2DM treatment; randomized controlled trial; parallel groups design; dietary intervention; functional olive oil

Outcome Measures

Primary Outcomes (1)

• HbA1c

  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 %

  1 year

Secondary Outcomes (81)

• Body weight

  1 year

• Body height

  1 year

• Body mass index (BMI)

  1 year

• Waist circumference

  1 year

• Hip circumference

  1 year

Study Arms (2)

OA-enriched functional olive oil

EXPERIMENTAL

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.

Dietary Supplement: OA-enriched functional olive oil

Control olive oil

ACTIVE COMPARATOR

Commercial olive oil (blend of virgin and refined olive oils) chosen by its very low content of bioactive minor components.

Dietary Supplement: commercial olive oil

Interventions

OA-enriched functional olive oil DIETARY_SUPPLEMENT

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).

Also known as: Functional olive oil enriched in Oleanolic acid

OA-enriched functional olive oil

commercial olive oil DIETARY_SUPPLEMENT

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.

Also known as: control olive oil

Control olive oil

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• community-residing men and women aged.
• Body Mass Index (BMI) between 25 and 39.9 kg/m2.
• diagnosed with T2DM \[Following the American Diabetes Association (ADA) 2019 criteria\] at least six months before being included in this trial.
• be treated with metformin (stable dose \>= 850 mg/day at least three months before recruitment) as monotherapy, or in combination with other hypoglycemic agents (administration of insulin exclusively in a single basal dose), except pioglitazone and sulphonylureas.
• be able to give voluntary informed consent and willing to comply with all study procedures.

You may not qualify if:

• suffering from Type 1 Diabetes Mellitus or latent autoimmune diabetes in adults.
• suffering from chronic kidney disease (estimated glomerular filtration rate (eGFR) \<30 ml/min/1.73m2).
• suffering from acute or chronic hepatitis, signs and symptoms of any liver disease other than non-alcoholic fatty liver disease (NAFLD), or ALT/AST ratio \>3 times the upper limit of the reference range.
• To present, at the time of recruitment, allergies and intolerances associated with food consumption.
• pregnant and lactating women.
• lack of willingness to use a highly effective contraceptive method (in women of childbearing potential).
• fasting triglyceridemia \> 600 mg/dL despite adequate treatment.
• grade 3 hypertension (systolic blood pressure ≥ 180 mm Hg and/or diastolic blood pressure ≥ 110 mm Hg) according to the 2018 guidelines of the European Society of Hypertension.
• use of pioglitazone or sulfonylureas.
• being treated with medications that promote weight loss (eg, Saxenda® \[liraglutide 3.0 mg\], Xenical® \[orlistat\], or similar over-the-counter \[OTC\] medications) within six months prior to the start of the trial.
• Being on chronic (\>14 days) therapy with systemic glucocorticoids (excluding topical, intraocular, intranasal, intra-articular, or inhaled preparations) within six months prior to enrollment.
• Presenting any of the following cardiovascular conditions within 6 months prior to study entry: acute myocardial infarction, unstable angina, New York Heart Association (NYHA) class III or class IV heart failure, or cerebrovascular accident.
• Evidence, in the investigators' opinion, of significant uncontrolled endocrine abnormality (e.g., thyrotoxicosis, adrenal crisis) at baseline.
• History of active or untreated malignancy, or being in remission from a clinically significant malignancy (other than basal or squamous cell skin cancer, cervical carcinoma in situ, or prostate cancer in situ) during the last 5 years before the study entry.
• Participation in the last 30 days in a clinical trial with an investigational product \[if the previous investigational product has a long half-life, 3 months or 5 half-lives (whichever is longer) should have passed\].

Sponsors & Collaborators

• Spanish National Research Council: lead
• Andalusian Health Service: collaborator
• Universidad Pablo de Olavide: collaborator

Study Sites (1)

Virgen del Rocío University Hospital

Seville, Andalicía, 41013, Spain

Location

Related Publications (4)

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

Related Links

• website of the OLTRAD Project (BIO-OLTRAD and OLTRAD trials

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Oleanolic Acid

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Pentacyclic Triterpenes; Triterpenes; Terpenes; Hydrocarbons; Organic Chemicals; Sapogenins

Study Officials

• José María Castellano, PhD

  Spanish National Research Council (CSIC)

  PRINCIPAL INVESTIGATOR

• Pedro Pablo García-Luna, MD

  Virgen del Rocío University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: prospective, parallel group, randomized, double-blind, controlled trial

Study Record Dates

• First Submitted: July 24, 2023
• First Posted: September 11, 2023
• Study Start: February 25, 2022
• Primary Completion: March 20, 2025
• Study Completion: June 30, 2025
• Last Updated: March 7, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)