Effect of Resveratrol Administration on Metabolic Syndrome, Insulin Sensitivity and Insulin Secretion

NCT02114892 | Completed Phase 2 Results

• 1 other identifier: RESV-MS
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

The Metabolic Syndrome is a high prevalence disease worldwide. About a quarter of the adult population suffers the disease. Resveratrol is a substance found in many plants, including grapes, nuts and wine, but it's also found in Polygonum cuspidatum. There is evidence that resveratrol consumption has beneficial effects on glucose and lipids metabolism, blood pressure and body weight. The aim of this study was to evaluate the effect of resveratrol on metabolic syndrome, insulin sensitivity and insulin secretion. The investigators hypothesis was that the administration of resveratrol modifies the metabolic syndrome, insulin sensitivity and insulin secretion.

Conditions

Metabolic Syndrome X

Keywords

metabolic syndrome; central obesity; resveratrol; insulin secretion; insulin sensitivity

Outcome Measures

Primary Outcomes (9)

• Triglycerides Levels at Week 12

  The triglycerides were evaluated at baseline and week 12 with enzymatic-colorimetric techniques and the entered values reflect the triglycerides level at week 12

  Week 12

• High Density Lipoprotein (c-HDL) Levels at Week 12.

  The c-HDL levels were evaluated at baseline and week 12 with enzymatic/colorimetric techniques and the entered values reflect the c-HDL level at week 12

  Baseline. Week 12

• Fasting Glucose Levels at Week 12.

  The fasting glucose levels were evaluated at baseline and week 12 with enzymatic/colorimetric techniques and the entered values reflect the fasting glucose level at week 12

  Week 12

• Systolic Blood Pressure at Week 12.

  The systolic blood pressure was evaluated at baseline and week 12 with a digital sphygmomanometer and the entered values reflect the systolic blood pressure at week 12

  Week 12

• First Phase of Insulin Secretion at Week 12.

  The first phase of insulin secretion was calculated at baseline and week 12 with Stumvoll index and the entered values reflect the first phase of insulin secretion at week 12

  Week 12

• Total Insulin Secretion at Week 12.

  The total insulin secretion was calculated at baseline and week 12 with insulinogenic index and the entered values reflect the total insulin secretion at week 12

  Week 12

• Total Insulin Sensitivity at Week 12.

  The insulin sensitivity was calculated at baseline and week 12 with Matsuda index and the entered values reflect the insulin sensitivity at week 12

  Week 12

• Waist Circumference at Week 12

  Waist circumference was evaluated at baseline and at week 12 with a flexible tape and the entered values reflect the waist circumference measure at week 12

  Week 12

• Diastolic Blood Pressure at Week 12

  The diastolic blood pressure was evaluated at baseline and week 12 with a digital sphygmomanometer and the entered values reflect the diastolic blood pressure at week 12

  Week 12

Secondary Outcomes (6)

• Weight at Week 12.

  Week 12

• Body Mass Index at Week 12

  Week 12

• Total Cholesterol at Week 12

  Week 12

• Low Density Lipoproteins (c-LDL) at Week 12

  Week 12

• Creatinine at Week 12.

  Baseline. Week 12.

Study Arms (2)

Resveratrol

EXPERIMENTAL

Resveratrol capsules, 500 mg, three times per day before meals during 90 days

Drug: Resveratrol

Placebo

PLACEBO COMPARATOR

Calcined magnesia capsules, 500 mg, three times per day before meals during 90 days

Drug: Placebo

Interventions

Resveratrol DRUG

Resveratrol capsules of 500 mg three times per day before meals with a total dosis of 1500 mg per day.

Also known as: Trans resveratrol, 3, 5, 4' -trihidroxiestilbeno

Resveratrol

Placebo DRUG

Calcined magnesia capsules, 500 mg, three times per day before meals with a total dose per day of 1500 mg

Also known as: Calcined magnesia

Placebo

Eligibility Criteria

• Age: 30 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Patients both sexes
• Age between 30 and 50 years
• Metabolic Syndrome according to the IDF criteria
• Waist circumference
• Man ≥90 cm
• Woman ≥80 cm
• And two of the following criteria:
• High density lipoprotein
• Man ≤40 mg/dL
• Woman ≤50 mg/dL
• Fasting glucose ≥100 mg/dL
• Triglycerides ≥150 mg/dL
• Blood pressure ≥130/85 mmHg
• Informed consent signed

You may not qualify if:

• Women with confirmed or suspected pregnancy
• Women under lactation and/or puerperium
• Hypersensibility to resveratrol
• Physical impossibility for taking pills
• Known uncontrolled renal, hepatic, heart or thyroid diseased
• Previous treatment for the metabolic syndrome components
• Body Mass Index ≥39.9 kg/m2
• Fasting glucose ≥126 mg/dL
• Triglycerides ≥500 mg/dL
• Total cholesterol ≥240 mg/dL
• Low density lipoprotein (c-LDL) ≥190 mg/dL
• Blood Pressure ≥140/90 mmHg

Sponsors & Collaborators

• University of Guadalajara: lead

Study Sites (1)

Intstituto de Terapeútica Experimental y Clínica. Centro Universitario de Ciencias de la Salud. Universidad de Guadalajara

Guadalajara, Jalisco, 45037, Mexico

Location

Related Publications (27)

• Beaudeux JL, Nivet-Antoine V, Giral P. Resveratrol: a relevant pharmacological approach for the treatment of metabolic syndrome? Curr Opin Clin Nutr Metab Care. 2010 Nov;13(6):729-36. doi: 10.1097/MCO.0b013e32833ef291.

  PMID: 20823772 BACKGROUND

• Szkudelska K, Szkudelski T. Resveratrol, obesity and diabetes. Eur J Pharmacol. 2010 Jun 10;635(1-3):1-8. doi: 10.1016/j.ejphar.2010.02.054. Epub 2010 Mar 19.

  PMID: 20303945 BACKGROUND

• Baur JA, Sinclair DA. Therapeutic potential of resveratrol: the in vivo evidence. Nat Rev Drug Discov. 2006 Jun;5(6):493-506. doi: 10.1038/nrd2060. Epub 2006 May 26.

  PMID: 16732220 BACKGROUND

• Timmers S, Auwerx J, Schrauwen P. The journey of resveratrol from yeast to human. Aging (Albany NY). 2012 Mar;4(3):146-58. doi: 10.18632/aging.100445.

  PMID: 22436213 BACKGROUND

• Kroon PA, Iyer A, Chunduri P, Chan V, Brown L. The Cardiovascular Nutrapharmacology of Resveratrol: Pharmacokinetics, Molecular Mechanisms and Therapeutic Potential. Curr Med Chem. 2010;17(23):2442-55. doi: 10.2174/092986710791556032.

  PMID: 20491649 BACKGROUND

• Baur JA. Resveratrol, sirtuins, and the promise of a DR mimetic. Mech Ageing Dev. 2010 Apr;131(4):261-9. doi: 10.1016/j.mad.2010.02.007. Epub 2010 Feb 26.

  PMID: 20219519 BACKGROUND

• Szkudelski T, Szkudelska K. Anti-diabetic effects of resveratrol. Ann N Y Acad Sci. 2011 Jan;1215:34-9. doi: 10.1111/j.1749-6632.2010.05844.x.

  PMID: 21261639 BACKGROUND

• Zhang J. Resveratrol inhibits insulin responses in a SirT1-independent pathway. Biochem J. 2006 Aug 1;397(3):519-27. doi: 10.1042/BJ20050977.

  PMID: 16626303 RESULT

• Rivera L, Moron R, Zarzuelo A, Galisteo M. Long-term resveratrol administration reduces metabolic disturbances and lowers blood pressure in obese Zucker rats. Biochem Pharmacol. 2009 Mar 15;77(6):1053-63. doi: 10.1016/j.bcp.2008.11.027. Epub 2008 Dec 3.

  PMID: 19100718 RESULT

• Hung LM, Chen JK, Huang SS, Lee RS, Su MJ. Cardioprotective effect of resveratrol, a natural antioxidant derived from grapes. Cardiovasc Res. 2000 Aug 18;47(3):549-55. doi: 10.1016/s0008-6363(00)00102-4.

  PMID: 10963727 RESULT

• Yu C, Shin YG, Chow A, Li Y, Kosmeder JW, Lee YS, Hirschelman WH, Pezzuto JM, Mehta RG, van Breemen RB. Human, rat, and mouse metabolism of resveratrol. Pharm Res. 2002 Dec;19(12):1907-14. doi: 10.1023/a:1021414129280.

  PMID: 12523673 RESULT

• Walle T, Hsieh F, DeLegge MH, Oatis JE Jr, Walle UK. High absorption but very low bioavailability of oral resveratrol in humans. Drug Metab Dispos. 2004 Dec;32(12):1377-82. doi: 10.1124/dmd.104.000885. Epub 2004 Aug 27.

  PMID: 15333514 RESULT

• Aumont V, Krisa S, Battaglia E, Netter P, Richard T, Merillon JM, Magdalou J, Sabolovic N. Regioselective and stereospecific glucuronidation of trans- and cis-resveratrol in human. Arch Biochem Biophys. 2001 Sep 15;393(2):281-9. doi: 10.1006/abbi.2001.2496.

  PMID: 11556815 RESULT

• Smoliga JM, Baur JA, Hausenblas HA. Resveratrol and health--a comprehensive review of human clinical trials. Mol Nutr Food Res. 2011 Aug;55(8):1129-41. doi: 10.1002/mnfr.201100143. Epub 2011 Jun 20.

  PMID: 21688389 RESULT

• Baur JA, Pearson KJ, Price NL, Jamieson HA, Lerin C, Kalra A, Prabhu VV, Allard JS, Lopez-Lluch G, Lewis K, Pistell PJ, Poosala S, Becker KG, Boss O, Gwinn D, Wang M, Ramaswamy S, Fishbein KW, Spencer RG, Lakatta EG, Le Couteur D, Shaw RJ, Navas P, Puigserver P, Ingram DK, de Cabo R, Sinclair DA. Resveratrol improves health and survival of mice on a high-calorie diet. Nature. 2006 Nov 16;444(7117):337-42. doi: 10.1038/nature05354. Epub 2006 Nov 1.

  PMID: 17086191 RESULT

• Fischer-Posovszky P, Kukulus V, Tews D, Unterkircher T, Debatin KM, Fulda S, Wabitsch M. Resveratrol regulates human adipocyte number and function in a Sirt1-dependent manner. Am J Clin Nutr. 2010 Jul;92(1):5-15. doi: 10.3945/ajcn.2009.28435. Epub 2010 May 12.

  PMID: 20463039 RESULT

• Baile CA, Yang JY, Rayalam S, Hartzell DL, Lai CY, Andersen C, Della-Fera MA. Effect of resveratrol on fat mobilization. Ann N Y Acad Sci. 2011 Jan;1215:40-7. doi: 10.1111/j.1749-6632.2010.05845.x.

  PMID: 21261640 RESULT

• Alberdi G, Rodriguez VM, Miranda J, Macarulla MT, Arias N, Andres-Lacueva C, Portillo MP. Changes in white adipose tissue metabolism induced by resveratrol in rats. Nutr Metab (Lond). 2011 May 10;8(1):29. doi: 10.1186/1743-7075-8-29.

  PMID: 21569266 RESULT

• Bruckbauer A, Zemel MB, Thorpe T, Akula MR, Stuckey AC, Osborne D, Martin EB, Kennel S, Wall JS. Synergistic effects of leucine and resveratrol on insulin sensitivity and fat metabolism in adipocytes and mice. Nutr Metab (Lond). 2012 Aug 22;9(1):77. doi: 10.1186/1743-7075-9-77.

  PMID: 22913271 RESULT

• Ramadori G, Gautron L, Fujikawa T, Vianna CR, Elmquist JK, Coppari R. Central administration of resveratrol improves diet-induced diabetes. Endocrinology. 2009 Dec;150(12):5326-33. doi: 10.1210/en.2009-0528. Epub 2009 Oct 9.

  PMID: 19819963 RESULT

• Szkudelski T. Resveratrol-induced inhibition of insulin secretion from rat pancreatic islets: evidence for pivotal role of metabolic disturbances. Am J Physiol Endocrinol Metab. 2007 Oct;293(4):E901-7. doi: 10.1152/ajpendo.00564.2006. Epub 2007 Jun 19.

  PMID: 17578889 RESULT

• Lagouge M, Argmann C, Gerhart-Hines Z, Meziane H, Lerin C, Daussin F, Messadeq N, Milne J, Lambert P, Elliott P, Geny B, Laakso M, Puigserver P, Auwerx J. Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha. Cell. 2006 Dec 15;127(6):1109-22. doi: 10.1016/j.cell.2006.11.013. Epub 2006 Nov 16.

  PMID: 17112576 RESULT

• Penumathsa SV, Thirunavukkarasu M, Zhan L, Maulik G, Menon VP, Bagchi D, Maulik N. Resveratrol enhances GLUT-4 translocation to the caveolar lipid raft fractions through AMPK/Akt/eNOS signalling pathway in diabetic myocardium. J Cell Mol Med. 2008 Dec;12(6A):2350-61. doi: 10.1111/j.1582-4934.2008.00251.x.

  PMID: 18266981 RESULT

• Dao TM, Waget A, Klopp P, Serino M, Vachoux C, Pechere L, Drucker DJ, Champion S, Barthelemy S, Barra Y, Burcelin R, Seree E. Resveratrol increases glucose induced GLP-1 secretion in mice: a mechanism which contributes to the glycemic control. PLoS One. 2011;6(6):e20700. doi: 10.1371/journal.pone.0020700. Epub 2011 Jun 6.

  PMID: 21673955 RESULT

• Brasnyo P, Molnar GA, Mohas M, Marko L, Laczy B, Cseh J, Mikolas E, Szijarto IA, Merei A, Halmai R, Meszaros LG, Sumegi B, Wittmann I. Resveratrol improves insulin sensitivity, reduces oxidative stress and activates the Akt pathway in type 2 diabetic patients. Br J Nutr. 2011 Aug;106(3):383-9. doi: 10.1017/S0007114511000316. Epub 2011 Mar 9.

  PMID: 21385509 RESULT

• Crandall JP, Oram V, Trandafirescu G, Reid M, Kishore P, Hawkins M, Cohen HW, Barzilai N. Pilot study of resveratrol in older adults with impaired glucose tolerance. J Gerontol A Biol Sci Med Sci. 2012 Dec;67(12):1307-12. doi: 10.1093/gerona/glr235. Epub 2012 Jan 4.

  PMID: 22219517 RESULT

• Szkudelski T. Resveratrol inhibits insulin secretion from rat pancreatic islets. Eur J Pharmacol. 2006 Dec 15;552(1-3):176-81. doi: 10.1016/j.ejphar.2006.09.046. Epub 2006 Sep 27.

  PMID: 17069794 RESULT

MeSH Terms

Conditions

Metabolic Syndrome; Obesity, Abdominal; Insulin Resistance

Interventions

Resveratrol

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Obesity; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Stilbestrols; Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polyphenols; Phenols

Results Point of Contact

• Title: Dr. Manuel González Ortiz
• Organization: Institute of Experimental andl Clinical Therapeutics

uiec@prodigy.net.mx

+52-33-10-58-52-00

Study Officials

• MANUEL GONZALEZ, PhD

  University of Guadalajara

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Researcher

Study Record Dates

• First Submitted: April 11, 2014
• First Posted: April 15, 2014
• Study Start: April 1, 2012
• Primary Completion: July 1, 2013
• Study Completion: September 1, 2013
• Last Updated: September 17, 2020
• Results First Posted: December 29, 2014

Record last verified: 2020-08

Locations

ME (1)