Effects of Hesperidin on Insulin Sensitivity

Obesity Clinical Trial

— EHIS  

Official title:

An Exploratory Study to Evaluate the Ability of the Citrus Polyphenol Hesperidin to Improve Insulin Sensitivity in Healthy Subjects and to Ameliorate Insulin Resistance in Obese Subjects

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01773486
• Other study ID #: HP-00051658
• Status: Withdrawn
• Phase: Phase 2
• Start date: June 2015
• Est. completion date: December 2015

Study information

• Verified date: February 2022
• Source: University of Maryland, Baltimore
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will examine whether hesperidin, a major component of citrus fruits, affects how the body responds to insulin in healthy and obese people. Laboratory studies suggest that hesperidin treatment lowers blood pressure, lowers blood sugar and increases blood flow. This study will see if hesperidin improves insulin resistance or insulin's effects on blood flow in people with insulin resistance.

Healthy normal weight or overweight people between 21 and 65 years of age may be eligible for this study. Participants are randomly assigned to take hesperidin or a placebo (inactive dummy pill ) for a 4-week treatment phase.

Description:

This study will examine whether hesperidin, a major component of citrus fruits, affects how the body responds to insulin in healthy and obese people. Insulin is not as effective in people who are overweight, have high blood pressure or diabetes. This condition is known as insulin resistance. Laboratory studies suggest that hesperidin treatment lowers blood pressure, lowers blood sugar and increases blood flow. This study will see if hesperidin improves insulin resistance or insulin's effects on blood flow in people with insulin resistance.

Healthy normal weight or overweight people between 21 and 65 years of age may be eligible for this study. Participants are randomly assigned to take hesperidin or a placebo (inactive dummy pill ) for a 4-week treatment phase. In addition to treatment, participants undergo the following procedures during the study period:

Screening, including medical history, physical examination and blood and urine tests.

Complete a dietary and physical activity questionnaire and consult with a dietitian

Blood and urine tests

At-home and clinic blood pressure monitoring

Glucose clamp test to measure how the body responds to insulin. This test is done two times during the study. A needle is placed in a vein in each of the subject's arms, one for sampling blood and the other for infusing insulin, glucose and potassium. Glucose and insulin levels, electrolytes, lipids, fatty acids, cytokines and hesperidin levels are measured. We will also use tracer-labeled glucose to determine how much glucose the body produces in the fasting state and during the clamp. This type of glucose has low levels of radiation.

Forearm blood flow measurement with finger plethysmography device. Before beginning the glucose clamp test, a test of how well the blood vessels relax is done. A device that measures the blood flow in the vessels of the forefingers is used. The test is performed at the before the glucose clamp test and again 2 hours after the beginning of the clamp.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: December 2015
• Est. primary completion date: December 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 21 Years to 65 Years

Eligibility

Inclusion Criteria:

Healthy Subjects - Men and women in good general health with no significant underlying illnesses who are between the ages of 21 - 65 years of age with HbA1C < 5.7 %, fasting blood glucose < 100 mg/dL, blood pressure less than 120/80, and BMI between 20 - 25 kg/m2. Subjects should have never smoked tobacco or not smoked within the previous year.

Obese Subjects - Men and women in good general health with no significant underlying illnesses except obesity who are between the ages of 21 - 65 years of age with HbA1C < 5.7 %, fasting blood glucose < 100 mg/dl, blood pressure less than 130/90, and BMI between 30 - 45 kg/m2.

Exclusion Criteria:

• Subjects will be excluded from our study if they are pregnant, breastfeeding, or if they plan pregnancy prior to the end of the study. In addition, subjects will be excluded if their age > 65 yrs, BMI = 45 kg/m2, or have liver disease (including liver transaminase levels greater than twice the upper limit of normal), pulmonary disease, renal insufficiency (serum creatinine greater than 2.0 mg/dl), coronary heart disease, heart failure (New York Heart Association heart failure Class III or IV), peripheral vascular disease, coagulopathy, Major depressive disorder, actively smoking or used tobacco within last year, history of cancer, in treatment for any form of cancer, positive tests for HIV, hepatitis B or C, or take systemic corticosteroids, thiazolidinediones (within 3 months), insulin, or anticoagulants, use food supplements that cannot be discontinued, regular intake of 8 or more cups of tea per week within 3 months prior to study entry, regular alcoholic beverage intake of more than two drinks per day (a drink corresponds to approximately 12 ounces of beer, 4 ounces of table wine, and between 1 and 1.5 ounces of 80-proof spirits), poor compliance during run-in period or regular use of medications that affect insulin sensitivity, blood pressure or vascular function and that cannot be discontinued. In addition, history of any other medical disease, laboratory abnormalities, or psychological conditions that would make the subject (based upon the principal investigator's judgment) unsuitable for study enrollment. Subjects will be excluded if they are unable to give informed consent for all procedures.

Related Conditions & MeSH terms

• Insulin Resistance
• Obesity

Intervention

Drug:
• Hesperidin
Citrus polyphenol, hesperidin
• Placebo
Placebo matching hesperidin

Locations

Country	Name	City	State
United States	University of Maryland	Baltimore	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
University of Maryland, Baltimore

Country where clinical trial is conducted

United States, 

References & Publications (1)

Rizza S, Muniyappa R, Iantorno M, Kim JA, Chen H, Pullikotil P, Senese N, Tesauro M, Lauro D, Cardillo C, Quon MJ. Citrus polyphenol hesperidin stimulates production of nitric oxide in endothelial cells while improving endothelial function and reducing inflammatory markers in patients with metabolic syndrome. J Clin Endocrinol Metab. 2011 May;96(5):E782-92. doi: 10.1210/jc.2010-2879. Epub 2011 Feb 23. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	pharmacokinetics	Determine steady-state levels of hesperidin before and after 1 month treatment with hesperidin or placebo. Determine hesperidin pharmacokinetics in plasma after oral administration of hesperidin (500 mg)	1 month
Primary	insulin sensitivity (determined by glucose clamp)	To determine if oral hesperidin consumption (500 mg p.o. daily for 1 month) improves insulin sensitivity (determined by glucose clamp) in healthy individuals or improves insulin resistance in subjects with obesity when compared with placebo treatment	1 month
Secondary	basal hepatic glucose production	Determine whether or not hesperidin treatment reduces basal hepatic glucose production in obese and lean subjects using tracer-labeled glucose.	1 month
Secondary	endothelial function	Determine if oral hesperidin consumption (500 mg p.o. daily for 1 month) improves baseline and insulin-stimulated endothelial function as measured by finger plethysmography via Endo-PAT (before and during glucose clamp studies)	1 month
Secondary	blood pressure	Determine if oral hesperidin treatment reduces systolic and/or diastolic blood pressure in obese and lean subjects.	1 month
Secondary	Inflammatory markers	Determine if oral hesperidin consumption (500 mg p.o. daily for 1 month) alters plasma levels of pro- and anti-inflammatory cytokines	1 month