Effects of Quercetin on Blood Sugar and Blood Vessel Function in Type 2 Diabetes.

NCT01839344 | Completed Phase 2

• 1 other identifier: 13A-1334
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to measure the effect of quercetin on glucose tolerance and postprandial endothelial function in comparison to placebo and Acarbose in participants with Type 2 Diabetes. Primary Hypothesis: We hypothesize that administration of quercetin (2g oral) prior to a 100g maltose tolerance test (MTT) will result in a decrease in postprandial blood glucose at 60 minutes compared to placebo. Acarbose (100mg oral), a pharmaceutical alpha-glucosidase inhibitor, will serve as a positive control. Secondary Hypothesis: We hypothesize that administration of quercetin (2g oral) will reduce the Area Under the Glucose Curve (AUC) for the 2 hours following a 100g MTT compared to placebo. AUC is hypothesized to be comparable between quercetin and Acarbose. Tertiary hypothesis: We hypothesize that administration of quercetin (2g oral) prior to a 100g MTT will result in a smaller reduction in flow mediated dilation (FMD) measured as an increase in Reactive Hyperemia Index (RHI) at 90 minutes compared to placebo.

Conditions

Diabetes Mellitus, Type 2

Keywords

hyperglycemia; Diabetes Mellitus, Type 2; endothelial dysfunction; quercetin; Acarbose; glucose tolerance; maltose

Outcome Measures

Primary Outcomes (1)

• Glucose tolerance following a maltose tolerance test

  Changes in serum glucose between fasting and 60 minutes after a maltose tolerance test will be calculated for each participant following each randomly assigned treatment. Mean difference in glucose will be calculated for the entire cohort and mean changes secondary to quercetin and Acarbose will be compared to placebo.

  Fasting (i.e., Time 0) and 60 minutes after a 100g maltose tolerance test

Secondary Outcomes (1)

• Area under the Glucose Curve (AUC)

  Fasting (i.e., Time 0), 30, 60 and 120 minutes after a 100g maltose tolerance test

Other Outcomes (1)

• Reactive Hyperemia Index (RHI)

  Fasting (i.e., Time 0) and 90 minutes after a 100g maltose tolerance test

Study Arms (3)

Quercetin

EXPERIMENTAL

Quercetin 250 mg capsules; oral single dose of 2000 mg

Dietary Supplement: Quercetin

Acarbose

ACTIVE COMPARATOR

Acarbose 100 mg tablet; oral single dose of 100 mg

Drug: Acarbose

Placebo

PLACEBO COMPARATOR

An oral single dose of a solid, colored empty capsule.

Drug: placebo

Interventions

Quercetin DIETARY_SUPPLEMENT

Quercetin 250 mg capsules; oral single dose of 2000 mg

Quercetin

Acarbose DRUG

Acarbose 100 mg tablet; oral single dose of 100 mg

Also known as: Precose

Acarbose

placebo DRUG

An oral single dose of a solid, colored empty capsule.

Placebo

Eligibility Criteria

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

You may qualify if:

• Adults aged 18-75 years with the International Classification of diseases book 9 (ICD-9) diagnosis of type 2 diabetes (250.XX). As lack of clarity in ICD-9 coding by providers is notorious in type 2 diabetes, we will specify ICD-9 diagnosis 250.XX in order to capture all subtypes of type 2 diabetes (see ICD-9 book for more information on subtypes).
• Patients on a stable dose (consistent dose for one month) of all medications and supplements.
• Hemoglobin A1c (HbA1c) of 6.5-10.5% within the last year. Since quercetin's effect on blood sugar and endothelial function may be related to its anti-oxidant properties, we are interested in looking at is effect on patients with higher levels of oxidative damage associated with higher blood sugars (i.e. elevated HbA1c \> 6.5%), yet we will exclude those with severe hyperglycemia.
• Stable exercise and diet for last 1 month.

You may not qualify if:

• Current use of quercetin.
• History of myocardial infarction within the last 6 months, angina, ischemic stroke, uncontrolled hypertension with systolic greater than 180 or diastolic greater than 110.
• Clinical or objective finding suggestive of congestive heart failure Class III or IV or shortness of breath with Activities of Daily Living (ADLs).
• Recent (\<14 days) history of infection. During the telephone screening, if patients have had an acute infection in the last 14 days they will be asked if we may recontact them in 3-4 weeks for a second telephone screening to determine qualification (including resolution of their recent infection \> 14 days).
• Stage IV or higher kidney disease (eGFR \< 30).
• Liver disease (defined as AST or ALT \> 2 x high normal (according to lab range)).
• Prior diagnosis of genetic abnormalities of carbohydrate metabolism (e.g. Congenital Sucrase-Isomaltase, Pompe Disease).
• Pregnant or breast feeding.
• Mental illness or other cognitive impairment prohibiting the candidate from making an informed choice (determined at the discretion of the PI in consult with the Research Assistants/Study Coordinator as needed) as assessed throughout telephone screening and informed consent process.
• Hypersensitivity to quercetin or Acarbose; based on past allergic symptoms taken with either drug or drug or supplement.
• Diagnosis of celiac disease/"sprue".
• Contraindications for EndoPAT:
• Participants on anti-platelet medications will be excluded if they have visible bruising (beyond petechiae).
• Participants will be excluded if they are unwilling to fast for 12 hours prior to maltose tolerance test and/or EndoPAT.
• Participants will be excluded if they have taken nitroglycerine, Cialis, or Viagra 12 hrs before test days.

Sponsors & Collaborators

• Bastyr University: lead

Study Sites (1)

Bastyr Center for Natural Health

Seattle, Washington, 98103, United States

Location

Related Publications (24)

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• Yee HS, Fong NT. A review of the safety and efficacy of acarbose in diabetes mellitus. Pharmacotherapy. 1996 Sep-Oct;16(5):792-805.

  PMID: 8888075 BACKGROUND

• Wascher TC, Schmoelzer I, Wiegratz A, Stuehlinger M, Mueller-Wieland D, Kotzka J, Enderle M. Reduction of postchallenge hyperglycaemia prevents acute endothelial dysfunction in subjects with impaired glucose tolerance. Eur J Clin Invest. 2005 Sep;35(9):551-7. doi: 10.1111/j.1365-2362.2005.01550.x.

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• Hanefeld M, Cagatay M, Petrowitsch T, Neuser D, Petzinna D, Rupp M. Acarbose reduces the risk for myocardial infarction in type 2 diabetic patients: meta-analysis of seven long-term studies. Eur Heart J. 2004 Jan;25(1):10-6. doi: 10.1016/s0195-668x(03)00468-8.

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• Shimabukuro M, Higa N, Chinen I, Yamakawa K, Takasu N. Effects of a single administration of acarbose on postprandial glucose excursion and endothelial dysfunction in type 2 diabetic patients: a randomized crossover study. J Clin Endocrinol Metab. 2006 Mar;91(3):837-42. doi: 10.1210/jc.2005-1566. Epub 2005 Dec 20.

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• Harwood M, Danielewska-Nikiel B, Borzelleca JF, Flamm GW, Williams GM, Lines TC. A critical review of the data related to the safety of quercetin and lack of evidence of in vivo toxicity, including lack of genotoxic/carcinogenic properties. Food Chem Toxicol. 2007 Nov;45(11):2179-205. doi: 10.1016/j.fct.2007.05.015. Epub 2007 Jun 7.

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• Jeong SM, Kang MJ, Choi HN, Kim JH, Kim JI. Quercetin ameliorates hyperglycemia and dyslipidemia and improves antioxidant status in type 2 diabetic db/db mice. Nutr Res Pract. 2012 Jun;6(3):201-7. doi: 10.4162/nrp.2012.6.3.201. Epub 2012 Jun 30.

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• Vessal M, Hemmati M, Vasei M. Antidiabetic effects of quercetin in streptozocin-induced diabetic rats. Comp Biochem Physiol C Toxicol Pharmacol. 2003 Jul;135C(3):357-64. doi: 10.1016/s1532-0456(03)00140-6.

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• Loke WM, Hodgson JM, Proudfoot JM, McKinley AJ, Puddey IB, Croft KD. Pure dietary flavonoids quercetin and (-)-epicatechin augment nitric oxide products and reduce endothelin-1 acutely in healthy men. Am J Clin Nutr. 2008 Oct;88(4):1018-25. doi: 10.1093/ajcn/88.4.1018.

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• Machha A, Achike FI, Mustafa AM, Mustafa MR. Quercetin, a flavonoid antioxidant, modulates endothelium-derived nitric oxide bioavailability in diabetic rat aortas. Nitric Oxide. 2007 Jun;16(4):442-7. doi: 10.1016/j.niox.2007.04.001. Epub 2007 Apr 20.

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• Ajay M, Achike FI, Mustafa AM, Mustafa MR. Effect of quercetin on altered vascular reactivity in aortas isolated from streptozotocin-induced diabetic rats. Diabetes Res Clin Pract. 2006 Jul;73(1):1-7. doi: 10.1016/j.diabres.2005.11.004. Epub 2005 Dec 27.

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• Ajay M, Achike FI, Mustafa AM, Mustafa MR. Direct effects of quercetin on impaired reactivity of spontaneously hypertensive rat aortae: comparative study with ascorbic acid. Clin Exp Pharmacol Physiol. 2006 Apr;33(4):345-50. doi: 10.1111/j.1440-1681.2006.04373.x.

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• Kim JH, Kang MJ, Choi HN, Jeong SM, Lee YM, Kim JI. Quercetin attenuates fasting and postprandial hyperglycemia in animal models of diabetes mellitus. Nutr Res Pract. 2011 Apr;5(2):107-11. doi: 10.4162/nrp.2011.5.2.107. Epub 2011 Apr 23.

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• Harano Y, Sakamoto A, Izumi K, Shimizu Y, Hoshi M. Usefulness of maltose for testing glucose tolerance. Am J Clin Nutr. 1977 Jun;30(6):924-31. doi: 10.1093/ajcn/30.6.924. No abstract available.

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• Hussain SA, Ahmed ZA, Mahwi TO, Aziz TA. Effect of quercetin on postprandial glucose excursion after mono- and disaccharides challenges in normal and diabetic rats. Journal of Diabetes Mellitus. 2012;2(1):82-87. Doi:10.4236/jdm.2012.21013

  BACKGROUND

• Hussain SA, Ahmed ZA, Mahwi TO, Aziz TA. Quercetin dampens postprandial hyperglycemia in type 2 diabetic patients challenged with carbohydrates load. International Journal of Diabetes Research. 2012;1(3):32-35.

  BACKGROUND

• St. Peter JV, Pirner MA, Halstenson CE, Brundage RC, Khan MA. No impact on oral quercetin on plasma glucose in patients with type 2 diabetes. FASEB Journal. 2011;25:meeting abstracts.

  BACKGROUND

• Acarbose: Drug information (monograph). In: Uptodate.com. Accessed December 22, 2012.

  BACKGROUND

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Hyperglycemia

Interventions

Quercetin; Acarbose

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Flavonols; Flavonoids; Chromones; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Trisaccharides; Oligosaccharides; Polysaccharides; Carbohydrates

Study Officials

• Ryan Bradley, ND, MPH

  Bastyr University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 22, 2013
• First Posted: April 24, 2013
• Study Start: May 1, 2013
• Primary Completion: March 1, 2014
• Study Completion: March 1, 2015
• Last Updated: March 18, 2015

Record last verified: 2014-02

Locations

US (1)