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Completed

NCT Number: NCT03648996

Sex-related Differences in Arterial Stiffness in Type 2 Diabetics: Role of Uric Acid

Three separate interventions will be undertaken with the primary outcome of improving pulse wave velocity. Initially, age and BMI-matched men and post-menopausal women, all with type 2 diabetes, will be treated with allopurinol (20 men, 20 women) for 6 months, in order to reduce serum uric acid (SUA) concentrations relative to placebo (10 men, 10 women). In a second intervention, dietary fructose will be restricted for a period of 6 months in type 2 diabetes (T2D) subjects who will maintain a stable weight (20 men, 20 women). In a third intervention, dietary fructose will be restricted for a period of 6 months in type 2 diabetes (T2D) subjects who will achieve a caloric deficit and weight reduction (20 men, 20 women). At the beginning and end of each of the studies, measures of arterial stiffness will be combined with assessments of endothelial function (flow-mediated dilation and insulin stimulated leg blood flow), measurements of systemic inflammation and oxidative stress.

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Key information

Conditions

Diabetes Mellitus, Type 2 Diabetes Mellitus Endocrine System Diseases Glucose Metabolism Disorders Hyperuricemia Metabolic Diseases Nutritional and Metabolic Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms

Age range

40 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

University of Missouri

Columbia, Missouri, 65212, United States

About this study

Sedentary, overweight and obese subjects diagnosed with T2D, ages 40-75 years old, will be recruited from the local community, via the University of Missouri's Endocrinology Clinic and the primary care clinics. During screening, and after consent, anthropometrics (waist circumference and body composition) will be obtained and fasting blood will be drawn for serum chemistries, A1c, complete blood count, liver and kidney function. Screening will also include completion of an oral glucose tolerance test with measurements of arterial stiffness and assessment of endothelial function. Following screening, eligible subjects will be assigned to one of the four groups (allopurinol, placebo, fructose restriction/isocaloric, or fructose restriction/hypocaloric). Allopurinol will be titrated to achieve a target dose of 300 mg/day. Along with placebo, this arm of the study is double-blinded. A separate group of men and women will be assigned to the isocaloric fructose-restriction study in which dietary fructose is replaced by starch and body weight is held constant. Lastly, a separate group of men and women will be assigned to the hypocaloric fructose-restriction in which baseline caloric intake will be reduced by 500 Calories/day while baseline intakes of protein and fat will remain constant. The subjects in these groups will not be blinded to the dietary treatment but the staff making measurements will be. Subjects in the four groups will be matched for age and BMI.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Men and women ages 40-75 years at randomization
  • BMI between 25.1 and 50 kg/m2.
  • Type 2 diabetes diagnosed > 3 months ago. Patients with T2D will be classified based on physician diagnosis.

Exclusion criteria

  • serum uric acid < 5.5 mg/dL (for medication/allopurinol and isocaloric low-fructose diet arm)
  • habitual diet containing low amount of sugars < 5% of total energy intake
  • recent CVD event (stroke, heart failure hospitalization, revascularization or acute coronary event in the last 12 months).
  • abnormal thyroid tests or chronic liver disease
  • stage IV renal disease (GFR <30)
  • hyperparathyroidism
  • use of azathioprine
  • active cancer
  • autoimmune diseases
  • excessive alcohol consumption (>14 drinks/week for men, >7 drinks/week for women)
  • current tobacco use
  • bodyweight change ≥10% within the last 6 months
  • history of gout or uncontrolled hypertension
  • A1C >10 % (only for medication/placebo arm)
  • Pregnancy or lactation in women (or women not using contraceptives)

Treatment and study plan

Low-fructose diet, isocaloric

Other

6 month of consumption a low fructose diet

Allopurinol

Drug

6 months of allopurinol treatment with the goal of decreasing uric acid compared to control group

Other names: Zyloprim

Placebo

Drug

6 months of placebo treatment

Low-fructose, hypocaloric

Other

6 month of consumption a low fructose diet with a 500 Calorie/day energy restriction

Primary outcomes

  1. Carotid Femoral Pulse Wave Velocity (cfPWV)

    Time frame: This will be assessed at baseline and 6 months (final). The goal is to assess changes from baseline when compared to final time point.

    It is the gold standard non-invasive index of arterial stiffness. Transit time between carotid and femoral pressure waves is calculated using the foot-to-foot method. cfPWV is calculated as distance traveled by the pulse wave (i.e., femoral location-sternal notch minus sternal notch-carotid location) divided by pulse transit time. All the measurements will be done by the same blinded technician

Secondary outcomes

  1. Brachial Artery Flow Mediated Dilation (FMD)

    Time frame: Baseline and 6 months (final). The goal is to assess changes from baseline when compared to final time point.

    Brachial artery FMD will be assessed at baseline and final. FMD is a measurement of conduit artery endothelial function. FMD is assessed immediately after each PWV measurement. Shear rate AUC until peak diameter is calculated as stimulus for FMD and used in covariate analysis as described. All measurements will be performed, under co-I supervision by the same blinded technician.

  2. Insulin-stimulated Leg Blood Flow

    Time frame: The goal is to assess insulin stimulated responses in blood flow after 6 mo of intervention.

    We will perform a hyperinsulinemic euglycemic clamp to evaluate insulin-stimulated leg blood flow (to be assessed via Doppler ultrasound). Insulin will be infused at a constant rate to mimic postprandial insulin concentrations and glucose maintained at fasting values via a variable 20% dextrose infusion. Femoral artery blood flow will be assessed at the beginning and at end of the 60-minute insulin infusion, and data are presented as percent of change from pre-insulin infusion values.

Sponsors and collaborators

Lead sponsor

University of Missouri-Columbia

Other

Registry information

Important dates

Study start
2018
Primary completion
2022
Study completion
2022
First posted
Aug 28, 2018
Registry last updated
Jul 3, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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