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Effects of Hesperidin on Insulin Sensitivity (EHIS)

Primary Purpose

Obesity, Insulin Resistance

Status
Withdrawn
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Hesperidin
Placebo
Sponsored by
University of Maryland, Baltimore
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Obesity focused on measuring Obesity, Insulin Resistance, Endothelial dysfunction, Blood pressure

Eligibility Criteria

21 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

  • University of Maryland

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Hesperidin

Placebo

Arm Description

Subjects will receive oral hesperidin 500 mg/day

subjects will receive matching placebo to hesperidin daily for 1 month

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

basal hepatic glucose production
Determine whether or not hesperidin treatment reduces basal hepatic glucose production in obese and lean subjects using tracer-labeled glucose.
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)
blood pressure
Determine if oral hesperidin treatment reduces systolic and/or diastolic blood pressure in obese and lean subjects.
Inflammatory markers
Determine if oral hesperidin consumption (500 mg p.o. daily for 1 month) alters plasma levels of pro- and anti-inflammatory cytokines

Full Information

First Posted
January 17, 2013
Last Updated
February 17, 2022
Sponsor
University of Maryland, Baltimore
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1. Study Identification

Unique Protocol Identification Number
NCT01773486
Brief Title
Effects of Hesperidin on Insulin Sensitivity
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
February 2022
Overall Recruitment Status
Withdrawn
Why Stopped
Not funded
Study Start Date
June 2015 (undefined)
Primary Completion Date
December 2015 (Actual)
Study Completion Date
December 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Maryland, Baltimore

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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.
Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Obesity, Insulin Resistance
Keywords
Obesity, Insulin Resistance, Endothelial dysfunction, Blood pressure

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Hesperidin
Arm Type
Active Comparator
Arm Description
Subjects will receive oral hesperidin 500 mg/day
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
subjects will receive matching placebo to hesperidin daily for 1 month
Intervention Type
Drug
Intervention Name(s)
Hesperidin
Intervention Description
Citrus polyphenol, hesperidin
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo matching hesperidin
Primary Outcome Measure Information:
Title
insulin sensitivity (determined by glucose clamp)
Description
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
Time Frame
1 month
Secondary Outcome Measure Information:
Title
basal hepatic glucose production
Description
Determine whether or not hesperidin treatment reduces basal hepatic glucose production in obese and lean subjects using tracer-labeled glucose.
Time Frame
1 month
Title
endothelial function
Description
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)
Time Frame
1 month
Title
blood pressure
Description
Determine if oral hesperidin treatment reduces systolic and/or diastolic blood pressure in obese and lean subjects.
Time Frame
1 month
Title
Inflammatory markers
Description
Determine if oral hesperidin consumption (500 mg p.o. daily for 1 month) alters plasma levels of pro- and anti-inflammatory cytokines
Time Frame
1 month
Other Pre-specified Outcome Measures:
Title
pharmacokinetics
Description
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)
Time Frame
1 month

10. Eligibility

Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kashif Munir, MD
Organizational Affiliation
University of Maryland, Baltimore
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Maryland
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
21346065
Citation
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.
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Effects of Hesperidin on Insulin Sensitivity

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