Exploring Unconventional Plant-Derived Metabolites for Glycemic Control: the Case of Pomegranate (EXPLORER)

The EXPLORER study will investigate whether supplementation with a pomegranate extract rich in ellagitannins is able to improve well-being and metabolic health in individuals without diabetes. The aim is to establish for the first time an association between the intake of ellagitanninsa and glycaemic control, the processing/aggregation of IAPP (a protein associated with diabetes), the state of the intestinal microbiota and circulating levels of urolithin B (a small bioavailable molecule resulting from the metabolism of ellagitannins).

This is a 12-week pilot study that is double-blind (neither participants nor researchers know who gets the treatment) and placebo-controlled (some people will receive a non-active substance). It will involve volunteers who do not have diabetes.

Phase 1 - Recruitment: Volunteers without diabetes, who are patients at a family health unit, will be recruited. Participants will provide informed consent and information such as sociodemographic and biochemical data.

Phase 2 - Intervention: The recruited individuals will be divided into two groups: one receiving the pomegranate extract supplement (intervention group) and the other receiving a placebo. In total, 60 participants will take part in the study.

Study Overview

• Status: Completed
• Conditions: Prediabetes
• Intervention / Treatment: Dietary supplement: EPS supplement intervention; Dietary supplement: Placebo

Detailed Description

A double-blinded, randomized, placebo-controlled pilot study was designed to assess the effect of Ellagitannins Pomegranate Supplements (EPS) in metabolic health of participants.

Participants will be recruited at the family health unit USF São Martinho de Alcabideche from the grouping of health centres ACES Cascais, and the study will be conducted according to universal bioethical principles.

At least 60 individuals with pre-diabetes will be included in the study. After the fulfilment of the inclusion criteria, they will be randomly assigned to the intervention group (IG) and the placebo group (PG). Equal distribution of gender, age and BMI will be ensured between the groups.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Portugal
  • Lisbon, Portugal, 1749-024
    • Lusofona University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Individuals without diabetes
• Both sexes
• Aged between 18 and 65
• Body Mass Index (BMI) less than 29.9 kg/m2
• Fasting plasma glucose levels below 126 mg/dL
• Haemoglobin A1C levels between 5.7 - 6.5%

Exclusion Criteria:

• Not agreeing to take part in the study
• BMI>30 kg/m2
• Being diagnosed with diabetes
• Having any type of cognitive disorder
• Using anti-diabetic medication
• Alcohol or drug abuse
• Pomegranate allergy
• Regular use of food supplements
• Difficulty swallowing tablets
• Being on, or planning to be on during the study period, a different diet than usual
• Pregnancy, planning to become pregnant during the study, breastfeeding 1 year before or during the study
• Oncological, cardiac, hepatic, renal, thyroid or other endocrine diseases
• Medical or social conditions that may affect adherence
• Participating in another study at the same time.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Supplement Intervention Group; 31 healthy individuals, male and female, were recruted at one family health unit, and randomly assigned to the intervention group, and were given for 12 weeks of one daily dose of 1.5 g powdered capsules of EPS.	Dietary supplement: EPS supplement intervention; 31 healthy individuals, male and female, were recruted at one family health unit, and randomly assigned to the intervention group, and were given for 12 weeks of one daily dose of 1.5 g powdered capsules of EPS.
Placebo Comparator: Placebo Group; 29 individuals with pre-diabetes, male and female, were recruted at one family health unit, and randomly assigned to the intervention group, and were given for 12 weeks of one daily dose of placebo supplement (cellulose).	Dietary supplement: Placebo; 29 healthy individuals, male and female, were recruted at one family health unit, and randomly assigned to the placebo group, and were given for 12 weeks of one daily dose of placebo.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Targeted metabolites - urolithins profiling	Urine sample	12 weeks
pro-IAPP	Blood sample	12 weeks
IAPP (Islet Amiloide Polipeptide)	Boold sample	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Short-chain fatty acids profiling	Blood sample	12 weeks

Collaborators and Investigators

• Sponsor: Regina Menezes
• Collaborators: Universidade Lusófona de Humanidades e Tecnologias
• Investigators: Principal Investigator: Regina Menezes, PhD, Lusofona University - CBIOS

Publications and helpful links

General Publications

• Stumvoll M, Goldstein BJ, van Haeften TW. Type 2 diabetes: principles of pathogenesis and therapy. Lancet. 2005 Apr 9-15;365(9467):1333-46. doi: 10.1016/S0140-6736(05)61032-X.
• Raimundo AF, Ferreira S, Tomas-Barberan FA, Santos CN, Menezes R. Urolithins: Diet-Derived Bioavailable Metabolites to Tackle Diabetes. Nutrients. 2021 Nov 27;13(12):4285. doi: 10.3390/nu13124285.
• Banihani SA, Makahleh SM, El-Akawi Z, Al-Fashtaki RA, Khabour OF, Gharibeh MY, Saadah NA, Al-Hashimi FH, Al-Khasieb NJ. Fresh pomegranate juice ameliorates insulin resistance, enhances beta-cell function, and decreases fasting serum glucose in type 2 diabetic patients. Nutr Res. 2014 Oct;34(10):862-7. doi: 10.1016/j.nutres.2014.08.003. Epub 2014 Aug 20.
• Mansoor K, Bardees R, Alkhawaja B, Mallah E, AbuQatouseh L, Schmidt M, Matalka K. Impact of Pomegranate Juice on the Pharmacokinetics of CYP3A4- and CYP2C9-Mediated Drugs Metabolism: A Preclinical and Clinical Review. Molecules. 2023 Feb 24;28(5):2117. doi: 10.3390/molecules28052117.
• Raimundo AF, Ferreira S, Pobre V, Lopes-da-Silva M, Brito JA, Dos Santos DJVA, Saraiva N, Dos Santos CN, Menezes R. Urolithin B: Two-way attack on IAPP proteotoxicity with implications for diabetes. Front Endocrinol (Lausanne). 2022 Dec 15;13:1008418. doi: 10.3389/fendo.2022.1008418. eCollection 2022.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2024
• Primary Completion (Actual): August 30, 2024
• Study Completion (Actual): September 30, 2024

Study Registration Dates

• First Submitted: August 7, 2024
• First Submitted That Met QC Criteria: October 24, 2024
• First Posted (Actual): October 26, 2024

Study Record Updates

• Last Update Posted (Actual): October 29, 2024
• Last Update Submitted That Met QC Criteria: October 25, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: prediabetes; Urolithins; Food supplement; beta-cell function; IAPP
• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Hyperglycemia; Prediabetic State; Glucose Intolerance
• Other Study ID Numbers: CE.ECTS/P05-24

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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