Effect of Totum-63 on Glucose and Lipid Homeostasis in Subjects With Dysglycemia (REVERSE-IT)

NCT04423302 | Completed DMC

• 2 other identifiers: PEC160752020-A00604-35
• Study Type: interventional
• Target: 636
• Locations: 7 countries
• Sites: 52

Brief Summary

This clinical study aims to assess the efficacy of TOTUM-63, a mix of 5 plant extracts, consumed at the daily regimen of three times per day on glucose and lipid homeostasis in dysglycemic subjects. The hypothesis is that TOTUM-63, consumed 3 times per day, is superior to placebo for decrease of fasting plasma glucose (FPG) concentration after 24 weeks of consumption.

Conditions

Prediabetic State; Diabetes type2; Dysglycemia

Keywords

Dysglycemia; Prediabetes; Type 2 diabetes; Hyperglycemia; Insulinemia; Diabetes risk; Diet supplement; Plant extracts; Health condition; Hygiene and dietary recommendations; Diet

Outcome Measures

Primary Outcomes (1)

• Fasting plasma glucose concentration at V3 with a 3 times a day regimen

  Fasting plasma glucose concentration in mg/dL, TOTUM-63 3/day vs placebo

  V3 (24 weeks of intervention)

Secondary Outcomes (25)

• Evolution of the fasting plasma glucose concentration

  V1 (baseline), V2 (12 weeks of intervention) and V3 (24 weeks of intervention)

• Evolution of the HbA1c

  V1 (baseline), V2 (12 weeks of intervention) and V3 (24 weeks of intervention)

• Evolution of the glycemia at 120 minutes following the 75g glucose intake

  V1 (baseline), V2 (12 weeks of intervention), V3 (24 weeks of intervention) and V4 (12 weeks and the end of intervention)

• Evolution of the fasting insulinemia

  V1 (baseline), V2 (12 weeks of intervention) and V3 (24 weeks of intervention)

• Evolution of the HOMA-IR (HOmeostasis Model Assessment of Insulin Resistance) index

  V1 (baseline), V2 (12 weeks of intervention) and V3 (24 weeks of intervention)

Study Arms (3)

TOTUM-63 3 intakes per day

EXPERIMENTAL

Experimental active diet supplement TOTUM-63 taken 3 times per day (blinded arm)

Dietary Supplement: TOTUM-63 3 intakes per day

Placebo 3 intakes per day

PLACEBO COMPARATOR

Placebo comparator taken 3 times per day (blinded arm)

Dietary Supplement: Placebo 3 intakes per day

TOTUM-63 2 intakes per day

EXPERIMENTAL

Experimental active diet supplement TOTUM-63 taken 2 times per day (open arm)

Dietary Supplement: TOTUM-63 2 intakes per day

Interventions

TOTUM-63 3 intakes per day DIETARY_SUPPLEMENT

5-g dose of TOTUM-63 diet supplement, a mix of 5 plant extracts. Eight capsules per day to consume orally in three intakes (3 in the morning, 2 at lunch and 3 at dinner)

Also known as: Active product 3 intakes per day

TOTUM-63 3 intakes per day

Placebo 3 intakes per day DIETARY_SUPPLEMENT

Placebo. Eight capsules per day to consume orally in three intakes (3 in the morning, 2 at lunch and 3 at dinner)

Also known as: Comparator product 3 intakes per day

Placebo 3 intakes per day

TOTUM-63 2 intakes per day DIETARY_SUPPLEMENT

5-g dose of TOTUM-63 diet supplement, a mix of 5 plant extracts. Eight capsules per day to consume orally in two intakes (4 in the morning and 4 at dinner)

Also known as: Active product 2 intakes per day

TOTUM-63 2 intakes per day

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• I1. From 18 to 70 years (including ranges);
• I2. Dysglycemic, prediabetic or newly diagnosed type 2 diabetes, subject without any clinical symptoms of diabetes (e.g. polyuria, polydipsia, blurred vision…) and not requiring immediate anti-diabetic treatment;
• I3. Body mass index (BMI) between 25 and 40 kg/m² (including ranges);
• I4. Waist circumference \> 102 cm for men and \> 88 cm for women (-2% margin allowed, respectively ≥ 100 cm and ≥ 86.5 cm);
• I5. Weight stable within ± 5% in the last three months;
• I6. No significant change in food habits or in physical activity in the 3 months before the randomization and agreeing to follow hygiene and dietary (HD) recommendations given during the study;
• I7. For women: Non-menopausal with the same reliable contraception since at least three months before the beginning of the study and agreeing to keep it during the entire duration of the study (hormonal contraception, intra uterine device or surgical intervention) or menopausal with or without hormone replacement therapy (estrogenic replacement therapy begun from less than 3 months excluded);
• I8. Good general and mental health according to the opinion of the investigator: no clinically significant and relevant abnormalities of medical history or physical examination;
• I9. Able and willing to participate to the study by complying with the protocol procedures as evidenced by his dated and signed informed consent form;
• I10. Affiliated with a social security scheme;
• I11. Agreeing to be registered on the volunteers in biomedical research (applicable only for French centers).
• At V0 biological analysis, the subjects will be eligible to the study on the following criteria:
• I12. Fasting plasma glucose concentration ≥ 110 mg/dL.

You may not qualify if:

• E1. Suffering from a metabolic disorder such as treated diabetes, uncontrolled thyroidal dysfunction or other metabolic disorder needing a dose adjustment in drug intervention according to the professional recommendations;
• E2. Suffering from an uncontrolled arterial hypertension (systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 100 mmHg);
• E3. With a history of retinopathy, ischemic cardiovascular event, having undergone recent surgical procedure in the past 6 months or in the 9 months to come;
• E4. Suffering from a severe chronic disease (e.g. cancer, HIV, renal failure, hepatic or biliary disorders ongoing, chronic inflammatory digestive disease, arthritis or other chronic respiratory trouble, etc.) or gastrointestinal disorders found to be inconsistent with the conduct of the study by the investigator (e.g. celiac disease);
• E5. Under antidiabetic drug (e.g. biguanides, sulfonylureas, glinides, gliptins, glitazones, gliflozins, α-glucosidase inhibitors, incretins and insulin);
• E6. Under lipid-lowering treatment (e.g. statins, fibrates, ezetimibe, bile acid sequestrants, niacin, etc.) since less than 3 months or modification of the treatment dose since less than 3 months before the randomization. Subject with a stable lipid-lowering treatment since at least three months can be included in the study;
• E7. Under medication which could affect glucose and/or lipid homeostasis parameters or stopped less than 3 months before randomization (e.g. beta 2 agonists like salbutamol, Angiotensin Converting Enzyme (ACE) inhibitors, beta blockers, thiazide diuretics, Selective Serotonin Reuptake Inhibitors (SSRIs), Mono-Amine Oxidase Inhibitors (MAOIs), neuroleptics, long-term corticosteroid systemic drugs, systemic antibodies, androgens, phenytoin, interferons, immunosuppressants, antivirals and antiretrovirals, etc.):
• Beta 2 agonists like salbutamol, ACE inhibitors, beta blockers, thiazide diuretics, SSRIs, MAOIs are tolerated only if stable since more than 3 months before the randomization and maintained during the whole study;
• The others drugs (neuroleptics, long-term corticosteroid systemic drugs, systemic antibodies, androgens, phenytoin, interferons, immunosuppressants, antivirals and antiretrovirals, etc.) are not allowed during the study;
• E8. Regular intake of dietary supplements or "health foods", or products rich in plant stanol or sterol (like Pro-Activ® or Danacol® products), rich in long chain omega-3 fatty acids (especially soft gels containing fish oils), or in other substances intended to reduce glycemia (e.g. beta-glucans, konjac, olive leaf extract, berberine, cinnamon, etc.) or stopped less than 3 months before the randomization;
• E9. Under treatment or dietary supplement which could significantly affect parameter(s) followed during the study according to the investigator or stopped in a too short period before the randomization (for example consumed in the month before the randomization);
• E10. With a known or suspected food allergy or intolerance or hypersensitivity to any of the study products' ingredient;
• E11. Consuming more than 3 standard drinks daily of alcoholic beverage for men or 2 standard drinks daily for women or not agreeing to keep his alcohol consumption habits unchanged throughout the study;
• E12. With extreme and/or unbalanced eating habits (e.g. vegetarian, vegan, skipping meals regularly);
• E13. With a personal history of anorexia nervosa, bulimia or significant eating disorders according to the investigator;

Sponsors & Collaborators

• Valbiotis: lead
• Biofortis Mérieux NutriSciences: collaborator

Study Sites (52)

MHAT-Botevgrad EOOD, Botevgrad

Botevgrad, Bulgaria

Location

MHAT Sveta Karidad, First department of Internal Diseases

Plovdiv, 4004, Bulgaria

Location

Ambulatory for IPSOC in Endocrynology and Metabolic Diseases ENDO MED-CONSULT EOOD

Plovdiv, Bulgaria

Location

Diagnostic-consultative center 7 EOOD, Plovdiv

Plovdiv, Bulgaria

Location

Diagnostic Consultative Center "ALEXANDROVSKA"

Sofia, 1431, Bulgaria

Location

University Multiprofile Hospital for active treatment "Alexandrovska" EAD Clinic of Endocrinology and metabolic diseases

Sofia, 1431, Bulgaria

Location

4th Multiprofile Hospital for active treatment - EAD, Internal Diseases Departement

Sofia, 1606, Bulgaria

Location

Diagnostic Consultative Center

Sofia, Bulgaria

Location

CHU Amiens

Amiens, 80054, France

Location

CH Arras

Arras, 62000, France

Location

CIC Clermont Ferrand

Clermont-Ferrand, 63000, France

Location

CEN Nutriment

Dijon, 21000, France

Location

Eurofins Optimed

Gières, 38610, France

Location

CHU Grenoble

Grenoble, 38043, France

Location

Institut Pasteur de Lille

Lille, 59019, France

Location

CHU Lille

Lille, 59037, France

Location

CHU Nantes

Nantes, 44093, France

Location

CHU Nice

Nice, 06202, France

Location

Unité d'Investigation Clinique Biofortis Mérieux NutriSciences

Paris, 75012, France

Location

Unité de Recherche Clinique en Immunologie Lyon Sud

Pierre-Bénite, 69310, France

Location

CHU Rouen

Rouen, 76000, France

Location

Biofortis Mérieux NutriSciences

Saint-Herblain, 44800, France

Location

Analyze & Realize

Berlin, 13467, Germany

Location

Klinische Forschung Dresden

Dresden, 01069, Germany

Location

Medizentrum Essen Borbeck

Essen, 45355, Germany

Location

Biotesys

Esslingen am Neckar, 73728, Germany

Location

Klinische Forschung Hamburg

Hamburg, 20253, Germany

Location

Klinische Forschung Hannover-Mitte

Hanover, 30159, Germany

Location

Klinische Forschung Karlsruhe

Karlsruhe, 76137, Germany

Location

Gemeinschaftspraxis Dr. Med C. Klein/J Minnich

Künzing, Germany

Location

Zentrum fur Klinische Studien

Sankt Ingbert, Germany

Location

Klinische Forschung Schwerin

Schwerin, 19055, Germany

Location

Zentrum für Klinische Ernährung Stuttgart

Stuttgart, 70599, Germany

Location

Drug Resesarch Center (DRC)

Balatonfüred, 8230, Hungary

Location

Trial Pharma Ltd

Békéscsaba, 5600, Hungary

Location

ClinExpert Medical Center

Budapest, 1033, Hungary

Location

Agria - Study Ltd

Eger, 3300, Hungary

Location

Trial Pharma Ltd

Győr, 9000, Hungary

Location

Trial Pharma Ltd

Gyula, 5703, Hungary

Location

Clinical Research Unit (CRU)

Miskolc, 3529, Hungary

Location

Trial Pharma Ltd

Orosháza, 5900, Hungary

Location

Azienda Ospedaliera Universitaria "Mater Domini"

Catanzaro, 88100, Italy

Location

IRCCS Ospedale San Raffaele

Milan, 20132, Italy

Location

Azienda Ospedaliera Universitaria Policlinico "Paolo Giaccone"

Palermo, 90127, Italy

Location

Policlinico Umberto I

Roma, 00161, Italy

Location

Vitamed

Bydgoszcz, Poland

Location

Grupowa Praktyka Lekarska s.c

Katowice, Poland

Location

Centrum Medyczne Linden

Krakow, Poland

Location

Sana Monitoring

Bucharest, Romania

Location

Spitalul Municipal Caracal

Caracal, Romania

Location

Ames Research Cente

Călăraşi, Romania

Location

Clintrial Medical Center

Reșca, Romania

Location

MeSH Terms

Conditions

Prediabetic State; Diabetes Mellitus, Type 2; Hyperglycemia

Condition Hierarchy (Ancestors)

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

Study Officials

• Isabelle METREAU, MD

  Biofortis Mérieux NutriSciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 2 blinded arms (Active 3 intakes per day and Placebo 3 intakes per day) and 1 open arm (Active 2 intakes per day)
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 28, 2020
• First Posted: June 9, 2020
• Study Start: July 8, 2020
• Primary Completion: January 31, 2023
• Study Completion: June 23, 2023
• Last Updated: September 21, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

BU (8); FR (14); IT (4); PL (3); DE (11); HU (8); RO (4)