Gender Differences in the Metabolic Effects of Uric Acid

NCT03076684 | Withdrawn Early Phase 1 FDA Drug

• 1 other identifier: 2007093
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Increased stiffening of the heart and blood vessels is a predictor of heart disease. Stiffening has been found to be greater in women than men, which puts women with poor blood sugar control at a greater risk for heart disease than men. In women only, a molecule in the blood called uric acid can be elevated due to diets high in fructose consumption and it is thought to be a cause of heart and vessel stiffening. From previous research, we have found that restricting fructose in the diet lowers uric acid more in women than men. There is also a drug that can be used to lower uric acid. These findings suggest a potential approach to decrease vessel and heart stiffness in women. The present study will investigate fructose restriction in the diet and drug treatment to lower uric acid in the blood and its effects on heart disease risk in women compared to men.

Conditions

Hyperuricemia

Outcome Measures

Primary Outcomes (1)

• vessel stiffness

  blood vessel stiffness is measured non-invasively with pulse wave velocity

  Change from baseline at 4 months

Study Arms (3)

low-fructose diet

EXPERIMENTAL

Intervention: low-fructose Subjects will consume a four-month diet with the goal of reducing added sugar intake from ≥13% of energy to \<5% of energy and keeping their weight stable.

Other: low-fructose diet

allopurinol treatment

EXPERIMENTAL

Subjects participating in the allopurinol treatment arm will begin with an initial dose of drug of 100 mg/d p.o. daily for 2 wks. The dose is then slowly increased over the next 8 wks to achieve a serum uric acid concentration of 6 mg/dL (maximum allopurinol dose is 800 mg/d). Once uric acid reaches 6 mg/dL, the subject stays on this dose and is seen for the interim visit (4 months), at which time all procedures are repeated. After this, drug treatment continues for another 4 months and the subject returns for the final visit at 8 months. The same procedures performed at baseline are repeated at this time. The dose of allopurinol will be taken the morning of the final visit.

Drug: Allopurinol

control arm

NO INTERVENTION

After completion of the baseline visit (procedures described above), subjects participating in the control arm are not seen again until the 4-month time point, when the same procedures performed at baseline are repeated, except for the MRI. Following this, they are seen again at 8-months, when all baseline procedures are repeated. Cardiac MRI and labeled water consumption occur at the baseline and final visits.

Interventions

low-fructose diet OTHER

Subjects will consume a four-month diet with the goal of reducing added sugar intake from ≥13% of energy to \<5% of energy and keeping their weight stable.

low-fructose diet

Allopurinol DRUG

Subjects in the drug arm will take the drug allopurinol daily.

allopurinol treatment

Eligibility Criteria

• Age: 40 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women with characteristics of the metabolic syndrome.
• years of age
• Overweight/obese subjects with BMI 25.1 - 40.0 kg/m2
• Pre-diabetes defined as fasting glucose 100 - 125 mg/dL or 2h glucose 140 - 200 mg/dL
• Habitual diets containing ≥ 13.0% of energy from added sugars
• Serum uric acid ≥ 7.0 mg/dL for men and women

You may not qualify if:

• Renal dysfunction (defined by glomerular filtration rate \[GFR\] \<60), abnormal thyroid function or liver disease
• Use of diuretics or azathioprine
• Diabetes defined as fasting glucose ≥ 125 mg/dL or HbA1c ≥ 7%
• Use of medications that interfere with lipid, protein, or carbohydrate metabolism, or occasional or regular tobacco use
• Habitual diets with low content of added sugars (\<5% of total energy)
• History of gout , gouty arthritis, or uncontrolled hypertension
• Pregnant
• Vegetarian food restrictions (the diets consumed contain some meat, eggs and dairy)
• Alcohol intake: females \> 70 g/wk, males \>140 g/wk
• Inability to have an MRI

Sponsors & Collaborators

• University of Missouri-Columbia: lead

Study Sites (1)

University of Missouri

Columbia, Missouri, 65212, United States

Location

MeSH Terms

Conditions

Hyperuricemia

Interventions

Allopurinol

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

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

Study Officials

• Elizabeth Parks, PhD

  University of Missouri-Columbia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professsor

Model Details: There are three arms of this study: a diet-treated group, a drug-treated group and a control group.

Study Record Dates

• First Submitted: March 1, 2017
• First Posted: March 10, 2017
• Study Start: March 3, 2017
• Primary Completion: December 1, 2018
• Study Completion: March 13, 2019
• Last Updated: April 17, 2019

Record last verified: 2019-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)