Clinical trial NCT01307917: Flavonoids in the Treatment of Endothelial Dysfunction in Children With Diabetes
Official title: Endothelial Dysfunction and the Role of Flavonoids in the Prevention of Nephropathy Among Pediatric Patients With Diabetes
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Diabetic Nephropathy
Endothelial Dysfunction
Keywords: diabetes mellitus
diabetic nephropathy
vascular endothelial dysfunction
flavonoids
flow-mediated dilation
Lead sponsor: Texas Tech University Health Sciences Center
Sponsor class: OTHER
First posted: 2011-03-03
Enrollment: 0
Sex: ALL
Minimum age (years): 12
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

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 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

Primary outcomes:
measure: 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.
timeFrame: day 0; day 14; day 21
Secondary outcomes:
measure: identify early markers in urine for vascular endothelial injury
timeFrame: screening, day 0, day 14, day 21
measure: examine the effects of flavonoids on vascular function, urine nitric oxide, and proinflammatory factors in patients with diabetes mellitus
timeFrame: day 0, day 14, day 21
Other outcomes:
Locations:
city: Amarillo
country: United States
facility: Texas Tech University Health Sciences Center School of Medicine
state: Texas
Study officials:
affiliation: Texas Tech University Health Sciences Center
name: Tetyana Vasylyeva, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: