Diabetes Mellitus, Type 2Phase 2NCT03648996
Sex-related Differences in Arterial Stiffness in Type 2 Diabetics: Role of Uric Acid
A Phase 2 study testing Low-fructose diet, isocaloric, Allopurinol and Low-fructose, hypocaloric in people with Diabetes Mellitus, Type 2 and Hyperuricemia, run by University of Missouri-Columbia at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 40 to 75 years
- Conditions the study is for
- Diabetes Mellitus, Type 2, Hyperuricemia
- What is being tested?
- Low-fructose diet, isocaloric, Allopurinol and Low-fructose, hypocaloric
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 34 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Nov 2018to 10 Mar 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 15Show fewer
- 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)
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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
- Being tested
- Low-fructose diet, isocaloric, Allopurinol, Placebo, Low-fructose, hypocaloric
- Keywords
- arterial stiffness, endothelial dysfunction, type 2 diabetes, hyperuricemia
- Medical subject headings
- Diabetes Mellitus, Type 2, Hyperuricemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Low-fructose diet, isocaloricOther
6 month of consumption a low fructose diet
AllopurinolDrug
Also called Zyloprim
6 months of allopurinol treatment with the goal of decreasing uric acid compared to control group
PlaceboDrug
6 months of placebo treatment
Low-fructose, hypocaloricOther
6 month of consumption a low fructose diet with a 500 Calorie/day energy restriction
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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) Receives: Drug: Allopurinol |
| Placebo | Placebo comparator | Subjects assigned to this arm will receive placebo Receives: 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. Receives: Other: Low-fructose, hypocaloric |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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)
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.
Measured: Baseline and 6 months (final). The goal is to assess changes from baseline when compared to final time point.
Insulin-stimulated Leg Blood Flow
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.
Measured: The goal is to assess insulin stimulated responses in blood flow after 6 mo of intervention.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Aug 2018
- Study start1 Nov 2018
- Primary completion10 Mar 2022
- Study completion10 Mar 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Diabetes Mellitus, Type 2Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Missouri-Columbia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Camila Manrique, MD, University of Missouri-Columbia
- Investigators
- Camila Manrique Acevedo, MD, Principal investigator, University of Missouri-Columbia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03648996
- Sponsor's protocol ID
- 2012106
- Status last verified
- Jun 2023
- First submitted
- 16 Aug 2018
- Last updated
- 3 Jul 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sex-related Differences in Arterial Stiffness in Type 2 Diabetics: Role of Uric Acid
- ClinicalTrials.gov ID
- NCT03648996
- Acronym / sponsor ID
- 2012106
- Conditions
- Diabetes Mellitus, Type 2, Hyperuricemia
- Keywords
- arterial stiffness, endothelial dysfunction, type 2 diabetes, hyperuricemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 34 participants (actual)
- Lead sponsor
- University of Missouri-ColumbiaUniversity, hospital or other
- Study start
- 1 Nov 2018 (actual)
- Primary completion
- 10 Mar 2022 (actual)
- Study completion
- 10 Mar 2022 (actual)
- First posted
- 28 Aug 2018 (actual)
- Results
- Posted 3 Jul 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Low-fructose diet, isocaloric | Experimental | Other: Low-fructose diet, isocaloricSubjects assigned to this arm of the study will consume for 6 months a diet low in fructose while maintaining baseline body weight. |
| Allopurinol | Experimental | Drug: AllopurinolSubjects assigned to this arm of the study will be treated for 6 months with allopurinol (max dose 300 mg) |
| Placebo | Placebo comparator | Drug: PlaceboSubjects assigned to this arm will receive placebo |
| Low-fructose diet, hypocaloric | Experimental | Other: Low-fructose, hypocaloricSubjects assigned to this arm of the study will consume for 6 months a diet low in fructose with a 500 Calorie energy reduction. |
Who may qualify
- Ages
- 40 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (15 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Low-fructose diet, isocaloric6 month of consumption a low fructose diet | Other | Low-fructose diet, isocaloric |
| AllopurinolAlso: Zyloprim6 months of allopurinol treatment with the goal of decreasing uric acid compared to control group | Drug | Allopurinol |
| Placebo6 months of placebo treatment | Drug | Placebo |
| Low-fructose, hypocaloric6 month of consumption a low fructose diet with a 500 Calorie/day energy restriction | Other | Low-fructose diet, hypocaloric |
Primary outcome
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
2 secondary outcomes
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.
Insulin-stimulated Leg Blood Flow
Time frame: The goal is to assess insulin stimulated responses in blood flow after 6 mo of intervention.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jul 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Camila Manrique Acevedo, MD principal investigator
University of Missouri-Columbia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Low-fructose diet, isocaloric, Allopurinol and Low-fructose, hypocaloric in people with Diabetes Mellitus, Type 2 and Hyperuricemia, run by University of Missouri-Columbia at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Jul 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jul 2023.