Cardiovascular Disease
Conditions
Keywords
childhood cancers, cardiovascular disease, childhood cancer survivor
Brief summary
Rationale: Survivors of childhood cancer are at an increased risk of developing cardiovascular risk factors as well as early cardiovascular disease, likely due to the intensive therapeutic regimen used to treat their cancer. Purple grape juice (PGJ) is a rich source of flavonoids and a powerful antioxidant. Clinical studies in both diseased and healthy adults suggest that daily consumption of PGJ contributes to increased antioxidant capacity, reduced low-density lipoprotein (LDL) oxidation, and improved vasodilation. Purpose: This randomized clinical trial is evaluating whether purple grape juice can reduce oxidative stress and improve the vascular health of survivors of childhood cancer in the early stages of cardiovascular disease.
Detailed description
Primary Objective: * To evaluate the effect of PGJ on endothelial function, a key measure of vascular health and considered a barometer for cardiovascular disease risk. Secondary Objective: * To evaluate the effect of PGJ on biomarkers of vascular and systemic oxidative stress. Outline: Patients undergo a 4-week washout period and refrain from consuming any type of juice, juice drink (less than 100% juice), wine or grapes. Patients are then randomized to 1 of 2 arms. Arm 1: Beginning in week 4, patients consume 6 ounces of purple grape juice (PGJ) twice daily for 4 weeks. Beginning in week 12, after a 4 week washout period, patients crossover to consume apple juice (AJ) as in Arm 2. Arm 2: Beginning in week 4, patients consume 6 ounces of AJ twice daily for 4 weeks. Beginning in week 12, after a 4 week washout period, patients crossover to consume PGJ as in Arm 1.
Interventions
OTHERPurple Grape Juice
6 ounces of purple grape juice consumed twice daily either during first or second 4 week supplementation period, depending on sequence randomization
OTHERApple Juice
6 ounces of clear apple juice consumed twice daily either during first or second 4 week supplementation period, depending on sequence randomization
Sponsors
University of Minnesota
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
10 Years to 30 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosed with cancer \> 5 years ago * Off-maintenance therapy for \> 36 months * Age 10-30 years * Reside within a 50 mile radius of the University of Minnesota
Exclusion criteria
* Pregnant or planning to become pregnant * Start of oral contraceptives \< or = 3 months prior to study enrollment * Current smoker * Diabetes (type 1 and 2) * Antibiotic use \< 2 weeks prior to study enrollment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Endothelial Function (Reactive Hyperemia Peripheral Arterial Tonometry (RH-PAT) Index Score) | 4 weeks (change since baseline) | Difference of least square means (95% Confidence Interval) in RH-PAT Index Scores between juice groups. Higher RH-PAT scores indicate better endothelial function; a positive difference of least square means is suggestive of an improvement in endothelial function. Probes were placed on the index fingers of both hands and a blood pressure cuff was placed on one arm. The cuff was inflated to suprasystolic pressure and the digital pulse volume was recorded before, during & after a 5 minute occlusion period. The ratio of the hyperemic and the baseline pulse amplitude (corrected for the same ratio on the control finger) was calculated and expressed as the RH-PAT index score. Lower scores reflect worse endothelial function. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Oxidized LDL | 4 weeks | Change from baseline in Oxidized LDL at 4 weeks, a biomarker of oxidative stress |
| Change in Myeloperoxidase (MPO) | 4 weeks | Change from baseline in Myeloperoxidase (MPO) at 4 weeks, a biomarker of oxidative stress |
| Change in High Sensitivity C-Reactive Protein (Hs-CRP) | 4 weeks | Change from baseline in high sensitivity C-Reactive Protein (hs-CRP) at 4 weeks, a biomarker of inflammation |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from the Metabolic Syndrome Study in Childhood Cancer Survivors and the Long-Term Follow-up Clinic, both at the University of Minnesota, Minneapolis, MN between October 2009 and May 2010.
Pre-assignment details
30 recruited; 6 drop-outs during 4 week run-in period, prior to randomization due to now-show for first clinic visit or concerns regarding time, compliance, or blood draws.
Participants by arm
| Arm | Count |
|---|---|
| Entire Study Population Includes groups randomized to receive purple grape juice first and apple juice first | 24 |
| Total | 24 |
Baseline characteristics
| Characteristic | Entire Study Population |
|---|---|
| Age, Categorical <=18 years | 19 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants |
| Age, Continuous | 15.8 years STANDARD_DEVIATION 2.6 |
| Body Mass Index | 22 kg/m^2 STANDARD_DEVIATION 3.2 |
| Diastolic blood pressure | 59 mmHg STANDARD_DEVIATION 8.3 |
| Fasting glucose | 78 mg/dL STANDARD_DEVIATION 7 |
| Fasting insulin | 6.3 mU/L STANDARD_DEVIATION 4.7 |
| Height | 165 Centimeters STANDARD_DEVIATION 11.6 |
| High-density lipoprotein (HDL) Cholesterol | 50 mg/dL STANDARD_DEVIATION 10.9 |
| Low-density lipoprotein (LDL) Cholesterol | 95 mg/dL STANDARD_DEVIATION 20.1 |
| Region of Enrollment United States | 24 participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 17 Participants |
| Systolic blood pressure | 111 mmHg STANDARD_DEVIATION 9.6 |
| Triglycerides | 78 mg/dL STANDARD_DEVIATION 33.7 |
| Weight | 60 kilograms STANDARD_DEVIATION 13.8 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 24 | 0 / 24 |
| serious Total, serious adverse events | 0 / 24 | 0 / 24 |
Outcome results
Primary
Change in Endothelial Function (Reactive Hyperemia Peripheral Arterial Tonometry (RH-PAT) Index Score)
Difference of least square means (95% Confidence Interval) in RH-PAT Index Scores between juice groups. Higher RH-PAT scores indicate better endothelial function; a positive difference of least square means is suggestive of an improvement in endothelial function. Probes were placed on the index fingers of both hands and a blood pressure cuff was placed on one arm. The cuff was inflated to suprasystolic pressure and the digital pulse volume was recorded before, during & after a 5 minute occlusion period. The ratio of the hyperemic and the baseline pulse amplitude (corrected for the same ratio on the control finger) was calculated and expressed as the RH-PAT index score. Lower scores reflect worse endothelial function.
Time frame: 4 weeks (change since baseline)
Population: Intent-to-Treat analysis
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Purple Grape Juice | Change in Endothelial Function (Reactive Hyperemia Peripheral Arterial Tonometry (RH-PAT) Index Score) | 0.06 units on a scale | Standard Error 0.089 |
| Apple Juice | Change in Endothelial Function (Reactive Hyperemia Peripheral Arterial Tonometry (RH-PAT) Index Score) | 0.22 units on a scale | Standard Error 0.093 |
p-value: 0.2595% CI: [-0.42, 0.11]Mixed Models Analysis
Secondary
Change in High Sensitivity C-Reactive Protein (Hs-CRP)
Change from baseline in high sensitivity C-Reactive Protein (hs-CRP) at 4 weeks, a biomarker of inflammation
Time frame: 4 weeks
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Purple Grape Juice | Change in High Sensitivity C-Reactive Protein (Hs-CRP) | 1.42 mg/L |
| Apple Juice | Change in High Sensitivity C-Reactive Protein (Hs-CRP) | 1.06 mg/L |
p-value: 0.3795% CI: [0.69, 2.62]Mixed Models Analysis
Secondary
Change in Myeloperoxidase (MPO)
Change from baseline in Myeloperoxidase (MPO) at 4 weeks, a biomarker of oxidative stress
Time frame: 4 weeks
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Purple Grape Juice | Change in Myeloperoxidase (MPO) | 0.95 ng/mL |
| Apple Juice | Change in Myeloperoxidase (MPO) | 1.03 ng/mL |
p-value: 0.1595% CI: [0.82, 1.03]Mixed Models Analysis
Secondary
Change in Oxidized LDL
Change from baseline in Oxidized LDL at 4 weeks, a biomarker of oxidative stress
Time frame: 4 weeks
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Purple Grape Juice | Change in Oxidized LDL | 4.66 Units/Liter | Standard Error 2.02 |
| Apple Juice | Change in Oxidized LDL | 1.57 Units/Liter | Standard Error 2.03 |
p-value: 0.2995% CI: [-2.73, 8.91]Mixed Models Analysis