- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03648996
Sex-related Differences in Arterial Stiffness in Type 2 Diabetics: Role of Uric Acid
June 30, 2023 updated by: Camila Manrique, MD, University of Missouri-Columbia
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
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.
Study Type
Interventional
Enrollment (Actual)
34
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Missouri
-
Columbia, Missouri, United States, 65212
- University of Missouri
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
40 years to 75 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
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)
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 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.
|
6 month of consumption a low fructose diet
|
Experimental: Allopurinol
Subjects assigned to this arm of the study will be treated for 6 months with allopurinol (max dose 300 mg)
|
6 months of allopurinol treatment with the goal of decreasing uric acid compared to control group
Other Names:
|
Placebo Comparator: Placebo
Subjects assigned to this arm will receive placebo
|
6 months of placebo treatment
|
Experimental: 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.
|
6 month of consumption a low fructose diet with a 500 Calorie/day energy restriction
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
Baseline and 6 months (final). The goal is to assess changes from baseline when compared to final time point.
|
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.
|
The goal is to assess insulin stimulated responses in blood flow after 6 mo of intervention.
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Camila Manrique Acevedo, MD, University of Missouri-Columbia
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
November 1, 2018
Primary Completion (Actual)
March 10, 2022
Study Completion (Actual)
March 10, 2022
Study Registration Dates
First Submitted
August 16, 2018
First Submitted That Met QC Criteria
August 23, 2018
First Posted (Actual)
August 28, 2018
Study Record Updates
Last Update Posted (Actual)
July 3, 2023
Last Update Submitted That Met QC Criteria
June 30, 2023
Last Verified
June 1, 2023
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Glucose Metabolism Disorders
- Metabolic Diseases
- Endocrine System Diseases
- Diabetes Mellitus
- Diabetes Mellitus, Type 2
- Hyperuricemia
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antirheumatic Agents
- Antimetabolites
- Protective Agents
- Antioxidants
- Free Radical Scavengers
- Gout Suppressants
- Allopurinol
Other Study ID Numbers
- 2012106
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
Yes
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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