Flavonoids in the Treatment of Endothelial Dysfunction in Children With Diabetes (flavonoid)

This study has been withdrawn prior to enrollment.
(No funding ever received)
Sponsor:
Information provided by (Responsible Party):
Texas Tech University Health Sciences Center
ClinicalTrials.gov Identifier:
NCT01307917
First received: November 15, 2010
Last updated: December 14, 2012
Last verified: December 2012
  Purpose

Diabetes is the most common metabolic disease of childhood. Vascular disease is a leading complication of diabetes, and attempts to maintain close glycemic control do not prevent the sequelae that claim the lives and quality of life of millions of diabetics each year. Up to forty percent of patients with diabetes mellitus ultimately develop diabetic nephropathy, the most common cause of end-stage renal disease requiring dialysis in the US. Flavonoid-rich diets are a promising intervention to prevent the endothelial dysfunction that apparently leads to this deadly complication. The mechanisms are still unclear but probably involve nitric oxide synthesis. The investigators hypothesize that early maintenance of the integrity of renal vasculature will significantly improve the lifelong prognosis for patients with diabetes. Flavonoids with anti-inflammatory and antioxidant activities could be used to protect endothelial function, and together with good glycemic control, prevent the development and progression of nephropathy. The investigators aims are to:

  1. compare endothelial function by studying reactive hyperemia, nitric oxide, and proinflammatory factors in adolescents (12-21 years old) with diabetes versus healthy sex- and age-matched control subjects.
  2. identify early markers in urine for vascular endothelial injury.
  3. examine the effects of flavonoids on vascular function, urine nitric oxide, and proinflammatory factors in patients with diabetes mellitus.

Condition Intervention
Diabetic Nephropathy
Endothelial Dysfunction
Dietary Supplement: flavonoids

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Endothelial Dysfunction and the Role of Flavonoids in the Prevention of Nephropathy Among Pediatric Patients With Diabetes

Resource links provided by NLM:


Further study details as provided by Texas Tech University Health Sciences Center:

Primary Outcome Measures:
  • compare endothelial function by studying reactive hyperemia, nitric oxide, and proinflammatory factors in adolescents (12-21 years old) with diabetes vs. healthy sex- and age-matched control subjects. [ Time Frame: day 0; day 14; day 21 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • identify early markers in urine for vascular endothelial injury [ Time Frame: screening, day 0, day 14, day 21 ] [ Designated as safety issue: No ]
  • examine the effects of flavonoids on vascular function, urine nitric oxide, and proinflammatory factors in patients with diabetes mellitus [ Time Frame: day 0, day 14, day 21 ] [ Designated as safety issue: No ]

Enrollment: 0
Study Start Date: July 2009
Study Completion Date: September 2012
Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: healthy controls high flavonoid
20 healthy adolescents (12-21 years old) receiving the flavonoid-rich capsule/supplement
Dietary Supplement: flavonoids
for 14 days, one dose two times per day, subjects will ingest a flavonoid-rich capsule containing 500 mg flavonoids or a placebo capsule made, stored, and dispensed by TTUHSC Pharmacy, with a similar look and taste.
Active Comparator: healthy controls low flavonoid
20 healthy adolescents (12-21 years old) receiving the placebo
Dietary Supplement: flavonoids
for 14 days, one dose two times per day, subjects will ingest a flavonoid-rich capsule containing 500 mg flavonoids or a placebo capsule made, stored, and dispensed by TTUHSC Pharmacy, with a similar look and taste.
Experimental: T1DM or T2DM high flavonoid
20 adolescents (12-21 years old) with Type 1 diabetes mellitus or Type 2 diabetes mellitus receiving the capsule/supplement
Dietary Supplement: flavonoids
for 14 days, one dose two times per day, subjects will ingest a flavonoid-rich capsule containing 500 mg flavonoids or a placebo capsule made, stored, and dispensed by TTUHSC Pharmacy, with a similar look and taste.
Active Comparator: T1DM or T2DM low flavonoid
20 adolescents (12-21 years old) with Type 1 diabetes mellitus or Type 2 diabetes mellitus receiving the placebo
Dietary Supplement: flavonoids
for 14 days, one dose two times per day, subjects will ingest a flavonoid-rich capsule containing 500 mg flavonoids or a placebo capsule made, stored, and dispensed by TTUHSC Pharmacy, with a similar look and taste.

Detailed Description:

Our proposal is the first attempt to use flavonoids to treat endothelial dysfunction as a causative factor of nephropathy in a pediatric population with diabetes. The investigators plan to recruit 40 adolescents with type 1 or 2 diabetes mellitus and 40 healthy peers into a double-blind, randomized, controlled study. Peripheral arterial tonometry, a noninvasive method to assess vascular status, will be employed to study endothelial function in both groups. Measurements of renal nitric oxide synthesis will be assayed using a nitric oxide chemiluminescence analyzer. Urinary protein microarray analyses will be conducted to assess early markers of kidney inflammation. The array is a multiplex sandwich fluorescent immunoassay for the simultaneous quantification of interleukin-1b (IL-1b), IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, interferon gamma, tumor necrosis factor-alpha, macrophage inflammatory protein-1-alpha and beta, and RANTES. The initial acute response and effect of 14 days of treatment with a flavonoid-rich capsulated supplement will be compared to a placebo. Study subjects will return for baseline assessments a week after the final flavonoid supplement to evaluate the sustainability of the response. Differences between group means for the measured variables before, during, and after the interventions will be tested for statistical significance using paired t-tests and nonparametric statistics. Univariate correlations will be calculated using Pearson's r.

  Eligibility

Ages Eligible for Study:   12 Years to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • adolescents 12 - 21 years old
  • with T1DM or T2DM and their healthy age- and sex-matched peers
  • DM subjects must maintain good glycemic control with HbA1C < 11

Exclusion Criteria:

  • no co-morbidities that could lead to inflammation or decline in renal function will be allowed
  • no non-steroidal anti-inflammatory drugs should be taken, for any reason, within 48 hours prior to the study days
  • no smoking will be permitted on the day of Pre-Study Evaluation or Study Days 0, 14, or 21
  • controls should not be taking any medications
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01307917

Locations
United States, Texas
Texas Tech University Health Sciences Center School of Medicine
Amarillo, Texas, United States, 79106
Sponsors and Collaborators
Texas Tech University Health Sciences Center
Investigators
Principal Investigator: Tetyana Vasylyeva, MD, PhD Texas Tech University Health Sciences Center
  More Information

No publications provided

Responsible Party: Texas Tech University Health Sciences Center
ClinicalTrials.gov Identifier: NCT01307917     History of Changes
Other Study ID Numbers: A09-3502
Study First Received: November 15, 2010
Last Updated: December 14, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Texas Tech University Health Sciences Center:
diabetes mellitus
diabetic nephropathy
vascular endothelial dysfunction
flavonoids
flow-mediated dilation

Additional relevant MeSH terms:
Diabetic Nephropathies
Kidney Diseases
Urologic Diseases
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases

ClinicalTrials.gov processed this record on August 19, 2014