Therapeutic Intervention of Eriomin Associated with Metformin in the Control of Hyperglycemia in Pre-Diabetic Patients

NCT06005142 | Active Not Recruiting DMC

• 1 other identifier: SaoPSU23
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

Citrus bioflavonoids, such as eriocitrin, hesperidin and naringin, have been shown improved hyperglycemia, insulin resistance and systemic inflammation, related to the development of type 2 diabetes. The nutraceutical Eriomin, a lemon flavonoid extract composed mainly by eriocitrin (70%) and other flavonoids (30%), improved the control of moderate hyperglycemia in pre-diabetic and diabetic patients without drug therapy. However, most patients with pre-diabetes are on oral biguanide (metformin) therapy, despite its limited efficacy (30-40%) on glycemic control and its undesirable gastrointestinal effects. Therefore, in the current study, Eriomin will be administered at a dose of 250 mg/d to adults diagnosed with pre-diabetes and being treated with metformin (1,000 mg/d). This clinical trial was designed as a placebo-control, double-blind, two-arm, crossover design. Clinical characteristics, body composition, food consumption, metabolic and inflammatory biomarkers and the microbiota of all patients will be evaluated before, during and at the end of the 12-week period (arm). Biochemical and metabolic parameters associated with prediabetes are expected to improve or return to normal with Eriomin in combination with metformin. At the same time, an increase in beneficial intestinal bacteria is expected, reducing pre-diabetic dysbiosis, and perhaps a noticeable improvement in body composition.

Conditions

Pre-diabetes

Keywords

citrus flavonoids; Eriomin; oral antidiabetic biguanide (metformin); hyperglycemia; microbiota

Outcome Measures

Primary Outcomes (1)

• Fasting Glycemia

  Dosages of glycemia concentration (mg/dL) before and after intervention with Eriomin/placebo

  0-12-18-26 week

Secondary Outcomes (12)

• Oral Glucose Tolerance Test (OGTT)

  0-12-18-26 week

• HbA1c

  0-12-18-26 week

• Insulin

  0-12-18-26 week

• Blood Lipids profile

  0-12-18-26 week

• Antioxidant Capacity

  0-12-18-26 week

Study Arms (2)

Eriomin/Placebo

ACTIVE COMPARATOR

Group A will receive Eriomin (250 mg/day) for 12 weeks, followed by a 2-week washout period, and then placebo (250 mg/day) for 12 weeks.

Dietary Supplement: Eriomin; Dietary Supplement: Washout; Dietary Supplement: Placebo

Placebo/Eriomin

PLACEBO COMPARATOR

Group B will receive placebo (250 mg/day) for 12 weeks, followed by a 2-week washout period, and then Eriomin (250 mg/day) for 12 weeks.

Dietary Supplement: Eriomin; Dietary Supplement: Washout; Dietary Supplement: Placebo

Interventions

Eriomin DIETARY_SUPPLEMENT

Pre-diabetic patients on oral biguanide (metformin) (1000 mg/day) will receive a 250 mg/day capsule of Eriomin for 12 weeks.

Eriomin/Placebo; Placebo/Eriomin

Washout DIETARY_SUPPLEMENT

After 12 weeks of treatment with the active component (Eriomin) or placebo, the participants will follow a washout for 2 weeks.

Eriomin/Placebo; Placebo/Eriomin

Placebo DIETARY_SUPPLEMENT

Pre-diabetic patients on oral biguanide (metformin) (1000 mg/day) will receive a 250 mg/day placebo capsule for 12 weeks.

Eriomin/Placebo; Placebo/Eriomin

Eligibility Criteria

• Age: 35 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Glycemia of 6.1 to 7.0 mmol / L
• Glycated hemoglobin with values between 5.7 and 6.4%

You may not qualify if:

• use of drugs, vitamins and dietary supplements, alcohol consumption (\> 20 g alcohol/d), and intense physical activity (\> 5 hours/week).
• History of cardiovascular disease, diabetes mellitus, liver, kidney or pancreatic disease

Sponsors & Collaborators

• Thais Cesar: lead
• Ingredients by Nature TM: collaborator

Study Sites (1)

Centro de Estudos e Praticas em Nutrição (CEPRAN)

Botucatú, São Paulo, 18618-689, Brazil

Location

Related Publications (10)

• Testa R, Bonfigli AR, Genovese S, De Nigris V, Ceriello A. The Possible Role of Flavonoids in the Prevention of Diabetic Complications. Nutrients. 2016 May 20;8(5):310. doi: 10.3390/nu8050310.

  PMID: 27213445 BACKGROUND

• Vinayagam R, Xu B. Antidiabetic properties of dietary flavonoids: a cellular mechanism review. Nutr Metab (Lond). 2015 Dec 23;12:60. doi: 10.1186/s12986-015-0057-7. eCollection 2015.

  PMID: 26705405 BACKGROUND

• Minato K, Miyake Y, Fukumoto S, Yamamoto K, Kato Y, Shimomura Y, Osawa T. Lemon flavonoid, eriocitrin, suppresses exercise-induced oxidative damage in rat liver. Life Sci. 2003 Feb 21;72(14):1609-16. doi: 10.1016/s0024-3205(02)02443-8.

  PMID: 12551749 BACKGROUND

• Hiramitsu M, Shimada Y, Kuroyanagi J, Inoue T, Katagiri T, Zang L, Nishimura Y, Nishimura N, Tanaka T. Eriocitrin ameliorates diet-induced hepatic steatosis with activation of mitochondrial biogenesis. Sci Rep. 2014 Jan 15;4:3708. doi: 10.1038/srep03708.

  PMID: 24424211 BACKGROUND

• Miyake Y, Shimoi K, Kumazawa S, Yamamoto K, Kinae N, Osawa T. Identification and antioxidant activity of flavonoid metabolites in plasma and urine of eriocitrin-treated rats. J Agric Food Chem. 2000 Aug;48(8):3217-24. doi: 10.1021/jf990994g.

  PMID: 10956094 BACKGROUND

• Ferreira PS, Spolidorio LC, Manthey JA, Cesar TB. Citrus flavanones prevent systemic inflammation and ameliorate oxidative stress in C57BL/6J mice fed high-fat diet. Food Funct. 2016 Jun 15;7(6):2675-81. doi: 10.1039/c5fo01541c. Epub 2016 May 16.

  PMID: 27182608 BACKGROUND

• Ribeiro CB, Ramos FM, Manthey JA, Cesar TB. Effectiveness of Eriomin(R) in managing hyperglycemia and reversal of prediabetes condition: A double-blind, randomized, controlled study. Phytother Res. 2019 Jul;33(7):1921-1933. doi: 10.1002/ptr.6386. Epub 2019 Jun 11.

  PMID: 31183921 BACKGROUND

• Cesar TB, Ramos FMM, Ribeiro CB. Nutraceutical Eriocitrin (Eriomin) Reduces Hyperglycemia by Increasing Glucagon-Like Peptide 1 and Downregulates Systemic Inflammation: A Crossover-Randomized Clinical Trial. J Med Food. 2022 Nov;25(11):1050-1058. doi: 10.1089/jmf.2021.0181. Epub 2022 Jul 7.

  PMID: 35796695 BACKGROUND

• Flory J, Lipska K. Metformin in 2019. JAMA. 2019 May 21;321(19):1926-1927. doi: 10.1001/jama.2019.3805.

  PMID: 31009043 BACKGROUND

• Cesar T, Oliveira MR, Sandrim V, Mendes A, Bruder R, Oliveira R, Sivieri K, Milenkovic D. Citrus flavonoid supplement enhances glycemic and metabolic control in prediabetic patients on metformin: a randomized controlled trial. Front Nutr. 2025 Aug 19;12:1639901. doi: 10.3389/fnut.2025.1639901. eCollection 2025.

  PMID: 40904779 DERIVED

MeSH Terms

Conditions

Glucose Intolerance; Hyperglycemia

Interventions

WASH protein, Drosophila

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Thais B Cesar, PhD

  São Paulo State University

  PRINCIPAL INVESTIGATOR

• Maria Rita M De Oliveira, PhD

  São Paulo State University

  STUDY DIRECTOR

• Valeria Cristina Samdrim, PhD

  São Paulo State University

  STUDY CHAIR

• Katia Sivieri, PhD

  São Paulo State University

  STUDY CHAIR

• Adriana Lucia Mendes, PhD

  São Paulo State University

  STUDY CHAIR

• Gabriela A Meira, Nutrition

  São Paulo State University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: All subjects and the principal investigator will remain blinded to treatment until data analysis is complete. Eriomin (lemon flavonoids extract) and Placebo (composed of microcrystalline corn starch) were encapsulated in tablets of the same size, shape, and color, by a registered pharmacist.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Visiting Professor

Model Details: A crossover, randomized, placebo-controlled, double-blind clinical trial will be conducted for 12 weeks, with a two-week washout interval, followed by another 12 weeks, totaling 26 weeks. All participants must be under oral biguanide (metformin) (1000 mg/day) regimen by at least two weeks before the intervention, and they will be measure for glycemia, HbA1c and OGTT, and an interview with an MD and Nutritionist in order to confirm eligibility, according to the inclusion/exclusion criteria. The selected individuals will be randomly distributed into 2 groups, and they will receive alternately Eriomin (or placebo), followed by 2-weeks of washout, and placebo (or Eriomin) for 12 weeks. At the beginning of the first, 12th, 14th, and 26th weeks, all subjects will be evaluated for the following: Glycemia, OGTT, HbA1c, Insulin, Lipids, TEAC, MDA, GLP-1, inflammatory, hepatic, kidney, and anthropometric parameters, and microbiota composition.

Study Record Dates

• First Submitted: March 27, 2023
• First Posted: August 22, 2023
• Study Start: January 15, 2024
• Primary Completion: December 30, 2024
• Study Completion: December 30, 2024
• Last Updated: November 29, 2024

Record last verified: 2024-11

Locations

BR (1)