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

NCT ID: NCT03648996

Last Updated: 2023-07-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 34 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-11-01
• Study Completion Date: 2022-03-10

Brief Summary

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.

Detailed Description

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.

Conditions

Diabetes Mellitus, Type 2; Hyperuricemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Low-fructose diet, isocaloric

Subjects assigned to this arm of the study will consume for 6 months a diet low in fructose while maintaining baseline body weight.

Group Type: EXPERIMENTAL

Low-fructose diet, isocaloric

Intervention Type: OTHER

6 month of consumption a low fructose diet

Allopurinol

Subjects assigned to this arm of the study will be treated for 6 months with allopurinol (max dose 300 mg)

Group Type: EXPERIMENTAL

Allopurinol

Intervention Type: DRUG

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

Placebo

Subjects assigned to this arm will receive placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

6 months of placebo treatment

Low-fructose diet, hypocaloric

Subjects assigned to this arm of the study will consume for 6 months a diet low in fructose with a 500 Calorie energy reduction.

Group Type: EXPERIMENTAL

Low-fructose, hypocaloric

Intervention Type: OTHER

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

Interventions

Low-fructose diet, isocaloric

6 month of consumption a low fructose diet

Intervention Type: OTHER

Allopurinol

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

Intervention Type: DRUG

Placebo

6 months of placebo treatment

Intervention Type: DRUG

Low-fructose, hypocaloric

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

Intervention Type: OTHER

Other Intervention Names

Zyloprim

Eligibility Criteria

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)

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Missouri-Columbia

OTHER

Sponsor Role: lead

Responsible Party

Camila Manrique, MD

Associate Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Camila Manrique Acevedo, MD

Role: PRINCIPAL_INVESTIGATOR

University of Missouri-Columbia

Locations

University of Missouri

Columbia, Missouri, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form: General

View Document

Document Type: Informed Consent Form: Allopurinol/Placebo Arm

View Document

Document Type: Informed Consent Form: Hypocaloric Low Fructose Diet Arm

View Document

Other Identifiers

2012106

Identifier Type: -

Identifier Source: org_study_id