Trial Outcomes & Findings for Sex-related Differences in Arterial Stiffness in Type 2 Diabetics: Role of Uric Acid (NCT NCT03648996)
NCT ID: NCT03648996
Last Updated: 2023-07-03
Results Overview
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
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
34 participants
Primary outcome timeframe
This will be assessed at baseline and 6 months (final). The goal is to assess changes from baseline when compared to final time point.
Results posted on
2023-07-03
Participant Flow
The current Clinical trials.gov information reflects the number of subjects that were recruited for the clinical trial portion of this study. No subjects were recruited the isocaloric portion of this study.
Participant milestones
| Measure |
Allopurinol
Subjects assigned to this arm of the study will be treated for 6 months with allopurinol (max dose 300 mg)
Allopurinol: 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
Placebo: 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.
Low-fructose, hypocaloric: 6 month of consumption a low fructose diet with a 500 Calorie/day energy restriction
|
|---|---|---|---|
|
Overall Study
STARTED
|
9
|
7
|
18
|
|
Overall Study
COMPLETED
|
7
|
5
|
16
|
|
Overall Study
NOT COMPLETED
|
2
|
2
|
2
|
Reasons for withdrawal
| Measure |
Allopurinol
Subjects assigned to this arm of the study will be treated for 6 months with allopurinol (max dose 300 mg)
Allopurinol: 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
Placebo: 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.
Low-fructose, hypocaloric: 6 month of consumption a low fructose diet with a 500 Calorie/day energy restriction
|
|---|---|---|---|
|
Overall Study
Withdrawal by Subject
|
0
|
2
|
2
|
|
Overall Study
Physician Decision
|
2
|
0
|
0
|
Baseline Characteristics
Measurement not available in all participants
Baseline characteristics by cohort
| Measure |
Allopurinol
n=7 Participants
Subjects assigned to this arm of the study will be treated for 6 months with allopurinol (max dose 300 mg)
Allopurinol: 6 months of allopurinol treatment with the goal of decreasing uric acid compared to control group
|
Placebo
n=5 Participants
Subjects assigned to this arm will receive placebo
Placebo: 6 months of placebo treatment
|
Low-fructose Diet, Hypocaloric
n=16 Participants
Subjects assigned to this arm of the study will consume for 6 months a diet low in fructose with a 500 Calorie energy reduction.
Low-fructose, hypocaloric: 6 month of consumption a low fructose diet with a 500 Calorie/day energy restriction
|
Total
n=28 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=16 Participants
|
0 Participants
n=28 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
5 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
9 Participants
n=16 Participants
|
18 Participants
n=28 Participants
|
|
Age, Categorical
>=65 years
|
2 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
7 Participants
n=16 Participants
|
10 Participants
n=28 Participants
|
|
Age, Continuous
|
60 years
STANDARD_DEVIATION 8.6 • n=7 Participants
|
58 years
STANDARD_DEVIATION 7.5 • n=5 Participants
|
59 years
STANDARD_DEVIATION 12.1 • n=16 Participants
|
59 years
STANDARD_DEVIATION 10.3 • n=28 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
9 Participants
n=16 Participants
|
15 Participants
n=28 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
7 Participants
n=16 Participants
|
13 Participants
n=28 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=16 Participants
|
1 Participants
n=28 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
7 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
15 Participants
n=16 Participants
|
27 Participants
n=28 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=16 Participants
|
0 Participants
n=28 Participants
|
|
Region of Enrollment
United States
|
7 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
16 Participants
n=16 Participants
|
28 Participants
n=28 Participants
|
|
Baseline PWV
|
9.87 m/s
STANDARD_DEVIATION 3.36 • n=7 Participants • Measurement not available in all participants
|
8.62 m/s
STANDARD_DEVIATION 1.45 • n=5 Participants • Measurement not available in all participants
|
8.17 m/s
STANDARD_DEVIATION 1.19 • n=15 Participants • Measurement not available in all participants
|
8.7 m/s
STANDARD_DEVIATION 2.06 • n=27 Participants • Measurement not available in all participants
|
|
Brachial FMD
|
4.75 Percentage (%)
STANDARD_DEVIATION 3.37 • n=7 Participants • Measurement not available in all participants
|
4.29 Percentage (%)
STANDARD_DEVIATION 0.77 • n=5 Participants • Measurement not available in all participants
|
5.15 Percentage (%)
STANDARD_DEVIATION 3.14 • n=13 Participants • Measurement not available in all participants
|
4.86 Percentage (%)
STANDARD_DEVIATION 2.83 • n=25 Participants • Measurement not available in all participants
|
PRIMARY outcome
Timeframe: This will be assessed at baseline and 6 months (final). The goal is to assess changes from baseline when compared to final time point.Population: Measurement not available for all subjects
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
Outcome measures
| Measure |
Allopurinol
n=6 Participants
Subjects assigned to this arm of the study will be treated for 6 months with allopurinol (max dose 300 mg)
Allopurinol: 6 months of allopurinol treatment with the goal of decreasing uric acid compared to control group
|
Placebo
n=4 Participants
Subjects assigned to this arm will receive placebo
Placebo: 6 months of placebo treatment
|
Low-fructose Diet, Hypocaloric
n=15 Participants
Subjects assigned to this arm of the study will consume for 6 months a diet low in fructose with a 500 Calorie energy reduction.
Low-fructose, hypocaloric: 6 month of consumption a low fructose diet with a 500 Calorie/day energy restriction
|
|---|---|---|---|
|
Carotid Femoral Pulse Wave Velocity (cfPWV)
|
8.71 m/s
Standard Deviation 1.47
|
7.8 m/s
Standard Deviation 1.04
|
8.28 m/s
Standard Deviation 1.40
|
SECONDARY outcome
Timeframe: Baseline and 6 months (final). The goal is to assess changes from baseline when compared to final time point.Population: Measurement not available for all subjects
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.
Outcome measures
| Measure |
Allopurinol
n=7 Participants
Subjects assigned to this arm of the study will be treated for 6 months with allopurinol (max dose 300 mg)
Allopurinol: 6 months of allopurinol treatment with the goal of decreasing uric acid compared to control group
|
Placebo
n=5 Participants
Subjects assigned to this arm will receive placebo
Placebo: 6 months of placebo treatment
|
Low-fructose Diet, Hypocaloric
n=16 Participants
Subjects assigned to this arm of the study will consume for 6 months a diet low in fructose with a 500 Calorie energy reduction.
Low-fructose, hypocaloric: 6 month of consumption a low fructose diet with a 500 Calorie/day energy restriction
|
|---|---|---|---|
|
Brachial Artery Flow Mediated Dilation (FMD)
|
5.03 Percentage (%)
Standard Deviation 3.44
|
4.4 Percentage (%)
Standard Deviation 2.8
|
7.10 Percentage (%)
Standard Deviation 2.19
|
SECONDARY outcome
Timeframe: The goal is to assess insulin stimulated responses in blood flow after 6 mo of intervention.Population: The percentage change in blood flow in response to insulin was calculated as femoral blood flow insulin - femoral blood flow insulin no insulin x 100
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.
Outcome measures
| Measure |
Allopurinol
n=7 Participants
Subjects assigned to this arm of the study will be treated for 6 months with allopurinol (max dose 300 mg)
Allopurinol: 6 months of allopurinol treatment with the goal of decreasing uric acid compared to control group
|
Placebo
n=5 Participants
Subjects assigned to this arm will receive placebo
Placebo: 6 months of placebo treatment
|
Low-fructose Diet, Hypocaloric
n=11 Participants
Subjects assigned to this arm of the study will consume for 6 months a diet low in fructose with a 500 Calorie energy reduction.
Low-fructose, hypocaloric: 6 month of consumption a low fructose diet with a 500 Calorie/day energy restriction
|
|---|---|---|---|
|
Insulin-stimulated Leg Blood Flow
|
-7.68 Percetage (%) change
Standard Deviation 35.29
|
68.18 Percetage (%) change
Standard Deviation 153.59
|
42.65 Percetage (%) change
Standard Deviation 75.12
|
Adverse Events
Allopurinol
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Low-fructose Diet, Hypocaloric
Serious events: 1 serious events
Other events: 8 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Allopurinol
n=7 participants at risk
Subjects assigned to this arm of the study will be treated for 6 months with allopurinol (max dose 300 mg)
Allopurinol: 6 months of allopurinol treatment with the goal of decreasing uric acid compared to control group
|
Placebo
n=5 participants at risk
Subjects assigned to this arm will receive placebo
Placebo: 6 months of placebo treatment
|
Low-fructose Diet, Hypocaloric
n=16 participants at risk
Subjects assigned to this arm of the study will consume for 6 months a diet low in fructose with a 500 Calorie energy reduction.
Low-fructose, hypocaloric: 6 month of consumption a low fructose diet with a 500 Calorie/day energy restriction
|
|---|---|---|---|
|
Infections and infestations
Urinary tract infection/pneumonia
|
0.00%
0/7 • 6 months
Subjects enrolled in the allopurinol/placebo arm were administered a safety formulary at weeks 2, 4, 6, 8,12, 16, and 20 to assess for common side effects. Subjects in the hypocaloric arm were contacted by the research team weekly from week 1 thru 6, and then at week 8, 12, 16, and 20 to assess for any changes in their health
|
0.00%
0/5 • 6 months
Subjects enrolled in the allopurinol/placebo arm were administered a safety formulary at weeks 2, 4, 6, 8,12, 16, and 20 to assess for common side effects. Subjects in the hypocaloric arm were contacted by the research team weekly from week 1 thru 6, and then at week 8, 12, 16, and 20 to assess for any changes in their health
|
6.2%
1/16 • Number of events 1 • 6 months
Subjects enrolled in the allopurinol/placebo arm were administered a safety formulary at weeks 2, 4, 6, 8,12, 16, and 20 to assess for common side effects. Subjects in the hypocaloric arm were contacted by the research team weekly from week 1 thru 6, and then at week 8, 12, 16, and 20 to assess for any changes in their health
|
Other adverse events
| Measure |
Allopurinol
n=7 participants at risk
Subjects assigned to this arm of the study will be treated for 6 months with allopurinol (max dose 300 mg)
Allopurinol: 6 months of allopurinol treatment with the goal of decreasing uric acid compared to control group
|
Placebo
n=5 participants at risk
Subjects assigned to this arm will receive placebo
Placebo: 6 months of placebo treatment
|
Low-fructose Diet, Hypocaloric
n=16 participants at risk
Subjects assigned to this arm of the study will consume for 6 months a diet low in fructose with a 500 Calorie energy reduction.
Low-fructose, hypocaloric: 6 month of consumption a low fructose diet with a 500 Calorie/day energy restriction
|
|---|---|---|---|
|
Gastrointestinal disorders
Diarrhea
|
57.1%
4/7 • 6 months
Subjects enrolled in the allopurinol/placebo arm were administered a safety formulary at weeks 2, 4, 6, 8,12, 16, and 20 to assess for common side effects. Subjects in the hypocaloric arm were contacted by the research team weekly from week 1 thru 6, and then at week 8, 12, 16, and 20 to assess for any changes in their health
|
40.0%
2/5 • 6 months
Subjects enrolled in the allopurinol/placebo arm were administered a safety formulary at weeks 2, 4, 6, 8,12, 16, and 20 to assess for common side effects. Subjects in the hypocaloric arm were contacted by the research team weekly from week 1 thru 6, and then at week 8, 12, 16, and 20 to assess for any changes in their health
|
0.00%
0/16 • 6 months
Subjects enrolled in the allopurinol/placebo arm were administered a safety formulary at weeks 2, 4, 6, 8,12, 16, and 20 to assess for common side effects. Subjects in the hypocaloric arm were contacted by the research team weekly from week 1 thru 6, and then at week 8, 12, 16, and 20 to assess for any changes in their health
|
|
Gastrointestinal disorders
Nausea
|
42.9%
3/7 • 6 months
Subjects enrolled in the allopurinol/placebo arm were administered a safety formulary at weeks 2, 4, 6, 8,12, 16, and 20 to assess for common side effects. Subjects in the hypocaloric arm were contacted by the research team weekly from week 1 thru 6, and then at week 8, 12, 16, and 20 to assess for any changes in their health
|
20.0%
1/5 • 6 months
Subjects enrolled in the allopurinol/placebo arm were administered a safety formulary at weeks 2, 4, 6, 8,12, 16, and 20 to assess for common side effects. Subjects in the hypocaloric arm were contacted by the research team weekly from week 1 thru 6, and then at week 8, 12, 16, and 20 to assess for any changes in their health
|
0.00%
0/16 • 6 months
Subjects enrolled in the allopurinol/placebo arm were administered a safety formulary at weeks 2, 4, 6, 8,12, 16, and 20 to assess for common side effects. Subjects in the hypocaloric arm were contacted by the research team weekly from week 1 thru 6, and then at week 8, 12, 16, and 20 to assess for any changes in their health
|
|
Skin and subcutaneous tissue disorders
Skin rash
|
28.6%
2/7 • 6 months
Subjects enrolled in the allopurinol/placebo arm were administered a safety formulary at weeks 2, 4, 6, 8,12, 16, and 20 to assess for common side effects. Subjects in the hypocaloric arm were contacted by the research team weekly from week 1 thru 6, and then at week 8, 12, 16, and 20 to assess for any changes in their health
|
40.0%
2/5 • 6 months
Subjects enrolled in the allopurinol/placebo arm were administered a safety formulary at weeks 2, 4, 6, 8,12, 16, and 20 to assess for common side effects. Subjects in the hypocaloric arm were contacted by the research team weekly from week 1 thru 6, and then at week 8, 12, 16, and 20 to assess for any changes in their health
|
0.00%
0/16 • 6 months
Subjects enrolled in the allopurinol/placebo arm were administered a safety formulary at weeks 2, 4, 6, 8,12, 16, and 20 to assess for common side effects. Subjects in the hypocaloric arm were contacted by the research team weekly from week 1 thru 6, and then at week 8, 12, 16, and 20 to assess for any changes in their health
|
|
Endocrine disorders
Non severe hypoglycemia
|
0.00%
0/7 • 6 months
Subjects enrolled in the allopurinol/placebo arm were administered a safety formulary at weeks 2, 4, 6, 8,12, 16, and 20 to assess for common side effects. Subjects in the hypocaloric arm were contacted by the research team weekly from week 1 thru 6, and then at week 8, 12, 16, and 20 to assess for any changes in their health
|
0.00%
0/5 • 6 months
Subjects enrolled in the allopurinol/placebo arm were administered a safety formulary at weeks 2, 4, 6, 8,12, 16, and 20 to assess for common side effects. Subjects in the hypocaloric arm were contacted by the research team weekly from week 1 thru 6, and then at week 8, 12, 16, and 20 to assess for any changes in their health
|
31.2%
5/16 • 6 months
Subjects enrolled in the allopurinol/placebo arm were administered a safety formulary at weeks 2, 4, 6, 8,12, 16, and 20 to assess for common side effects. Subjects in the hypocaloric arm were contacted by the research team weekly from week 1 thru 6, and then at week 8, 12, 16, and 20 to assess for any changes in their health
|
|
Endocrine disorders
Glucosuria
|
0.00%
0/7 • 6 months
Subjects enrolled in the allopurinol/placebo arm were administered a safety formulary at weeks 2, 4, 6, 8,12, 16, and 20 to assess for common side effects. Subjects in the hypocaloric arm were contacted by the research team weekly from week 1 thru 6, and then at week 8, 12, 16, and 20 to assess for any changes in their health
|
0.00%
0/5 • 6 months
Subjects enrolled in the allopurinol/placebo arm were administered a safety formulary at weeks 2, 4, 6, 8,12, 16, and 20 to assess for common side effects. Subjects in the hypocaloric arm were contacted by the research team weekly from week 1 thru 6, and then at week 8, 12, 16, and 20 to assess for any changes in their health
|
6.2%
1/16 • 6 months
Subjects enrolled in the allopurinol/placebo arm were administered a safety formulary at weeks 2, 4, 6, 8,12, 16, and 20 to assess for common side effects. Subjects in the hypocaloric arm were contacted by the research team weekly from week 1 thru 6, and then at week 8, 12, 16, and 20 to assess for any changes in their health
|
|
Musculoskeletal and connective tissue disorders
Ankle Sprain
|
0.00%
0/7 • 6 months
Subjects enrolled in the allopurinol/placebo arm were administered a safety formulary at weeks 2, 4, 6, 8,12, 16, and 20 to assess for common side effects. Subjects in the hypocaloric arm were contacted by the research team weekly from week 1 thru 6, and then at week 8, 12, 16, and 20 to assess for any changes in their health
|
0.00%
0/5 • 6 months
Subjects enrolled in the allopurinol/placebo arm were administered a safety formulary at weeks 2, 4, 6, 8,12, 16, and 20 to assess for common side effects. Subjects in the hypocaloric arm were contacted by the research team weekly from week 1 thru 6, and then at week 8, 12, 16, and 20 to assess for any changes in their health
|
6.2%
1/16 • 6 months
Subjects enrolled in the allopurinol/placebo arm were administered a safety formulary at weeks 2, 4, 6, 8,12, 16, and 20 to assess for common side effects. Subjects in the hypocaloric arm were contacted by the research team weekly from week 1 thru 6, and then at week 8, 12, 16, and 20 to assess for any changes in their health
|
|
Gastrointestinal disorders
Acid Reflux
|
0.00%
0/7 • 6 months
Subjects enrolled in the allopurinol/placebo arm were administered a safety formulary at weeks 2, 4, 6, 8,12, 16, and 20 to assess for common side effects. Subjects in the hypocaloric arm were contacted by the research team weekly from week 1 thru 6, and then at week 8, 12, 16, and 20 to assess for any changes in their health
|
0.00%
0/5 • 6 months
Subjects enrolled in the allopurinol/placebo arm were administered a safety formulary at weeks 2, 4, 6, 8,12, 16, and 20 to assess for common side effects. Subjects in the hypocaloric arm were contacted by the research team weekly from week 1 thru 6, and then at week 8, 12, 16, and 20 to assess for any changes in their health
|
6.2%
1/16 • 6 months
Subjects enrolled in the allopurinol/placebo arm were administered a safety formulary at weeks 2, 4, 6, 8,12, 16, and 20 to assess for common side effects. Subjects in the hypocaloric arm were contacted by the research team weekly from week 1 thru 6, and then at week 8, 12, 16, and 20 to assess for any changes in their health
|
|
Metabolism and nutrition disorders
Severe hypoglycemia
|
0.00%
0/7 • 6 months
Subjects enrolled in the allopurinol/placebo arm were administered a safety formulary at weeks 2, 4, 6, 8,12, 16, and 20 to assess for common side effects. Subjects in the hypocaloric arm were contacted by the research team weekly from week 1 thru 6, and then at week 8, 12, 16, and 20 to assess for any changes in their health
|
0.00%
0/5 • 6 months
Subjects enrolled in the allopurinol/placebo arm were administered a safety formulary at weeks 2, 4, 6, 8,12, 16, and 20 to assess for common side effects. Subjects in the hypocaloric arm were contacted by the research team weekly from week 1 thru 6, and then at week 8, 12, 16, and 20 to assess for any changes in their health
|
0.00%
0/16 • 6 months
Subjects enrolled in the allopurinol/placebo arm were administered a safety formulary at weeks 2, 4, 6, 8,12, 16, and 20 to assess for common side effects. Subjects in the hypocaloric arm were contacted by the research team weekly from week 1 thru 6, and then at week 8, 12, 16, and 20 to assess for any changes in their health
|
Additional Information
Dr. Camila Manrique, MD
University of Missouri, School of Medicine
Phone: (573) 882-2554
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place