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

NCT03648996 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 2012106
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

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.

Conditions

Diabetes Mellitus, Type 2; Hyperuricemia

Keywords

arterial stiffness; endothelial dysfunction; type 2 diabetes; hyperuricemia

Outcome Measures

Primary Outcomes (1)

• Carotid Femoral Pulse Wave Velocity (cfPWV)

  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

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

Secondary Outcomes (2)

• Brachial Artery Flow Mediated Dilation (FMD)

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

• Insulin-stimulated Leg Blood Flow

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

Study Arms (4)

Low-fructose diet, isocaloric

EXPERIMENTAL

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

Other: Low-fructose diet, isocaloric

Allopurinol

EXPERIMENTAL

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

Drug: Allopurinol

Placebo

PLACEBO COMPARATOR

Subjects assigned to this arm will receive placebo

Drug: Placebo

Low-fructose diet, hypocaloric

EXPERIMENTAL

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

Other: Low-fructose, hypocaloric

Interventions

Low-fructose diet, isocaloric OTHER

6 month of consumption a low fructose diet

Low-fructose diet, isocaloric

Allopurinol DRUG

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

Also known as: Zyloprim

Allopurinol

Placebo DRUG

6 months of placebo treatment

Placebo

Low-fructose, hypocaloric OTHER

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

Low-fructose diet, hypocaloric

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• University of Missouri-Columbia: lead

Study Sites (1)

University of Missouri

Columbia, Missouri, 65212, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Hyperuricemia

Interventions

Allopurinol

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

The covid pandemic limited recruitment efforts. Protocol was modified to limit the risk of exposure of research staff and research participants.

Results Point of Contact

• Title: Dr. Camila Manrique, MD
• Organization: University of Missouri, School of Medicine

manriquec@umsystem.edu

(573) 882-2554

Study Officials

• Camila Manrique Acevedo, MD

  University of Missouri-Columbia

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: August 16, 2018
• First Posted: August 28, 2018
• Study Start: November 1, 2018
• Primary Completion: March 10, 2022
• Study Completion: March 10, 2022
• Last Updated: July 3, 2023
• Results First Posted: July 3, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)