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The purpose of this study is to investigate the short-term effects of a reduced fat plant-based diet on biomarkers of inflammation, oxidative stress and cardiovascular risk. This plant-based diet consists of whole grains, fruits and vegetables and little amounts of nuts and seeds, with no limitations on the amount of food intake. Animal products are not allowed. The results of the plant-based diet will be compared with the diet recommended by American Heart Association. This diet also emphasizes fruits and vegetables, but allows healthy fats, low-fat meats, fish and low-fat dairy in moderation. The results of the study might be useful in understanding whether or not plant-based diets are protective against cardiovascular disease.
Scientific Question: In obese, hypercholesterolemic (>169 mg/dl) 9-18 year olds and one of their parents are biomarkers of inflammation, oxidative stress and cardiovascular risk significantly reduced after a randomized 4 week trial of a reduced fat, vegan diet, or the American Heart Association (AHA) diet (which also encourages fruits, vegetables and whole grains, but permits low fat meat and dairy, and fish)? Rationale: "Cardiovascular disease remains the leading cause of death in North Americans, but manifest disease in childhood and adolescence is rare. By contrast, risk factors and risk behaviors that accelerate the development of atherosclerosis begin in childhood, and there is increasing evidence that risk reduction delays progression toward clinical disease". Myeloperoxidase is an early biomarker of inflammation, oxidative stress and cardiovascular risk in prepubertal obese children and is over expressed in children with hypercholesterolemia. Trimethylamine N-oxide, global arginine bioavailability ratio, arginine methylation index, paraoxonase 1 gene, and F2-isoprostane are all also associated with future major adverse cardiovascular events. Studies have suggested that a low-fat, vegan diet is effective in promoting weight loss, lowering body mass index, improving lipoprotein profiles, insulin sensitivity and in preventing cardiovascular disease in overweight individuals. Vegetarian diets have been shown to not only prevent but also to reverse heart disease in adults. Dietary habits (e.g. vegan/vegetarian versus omnivore/carnivore) are associated with significant alterations in intestinal microbiota composition and function. The diet-microbe interaction may play a significant role in the cardiovascular protective effects of a vegan/vegetarian diet. One small report of 15 adults on a reduced fat, vegan "Engine 2 Diet" for four weeks reported decreases in mean total cholesterol from 197 mg/dl to 135 mg/dl and mean LDL cholesterol falling from 124 mg/dl to 74 mg/dl.
Innovation: This is the first randomized trial comparing a low fat vegan diet to the standard AHA diet. If one diet proves superior in this brief pilot study, future larger long term studies will be needed to clearly define the health implications of our results.
Methods: Obese hypercholesterolemic children ages 9-18 will be identified by reviewing medical records and recruited initially by letters. Child, parent/guardian pairs will be randomly assigned to either the reduced fat vegan diet or the AHA diet.
During the 4-week study, participants will be asked to attend a group teaching and cooking session once a week on Saturday to learn about their assigned diets. The participants will also be requested to record their diet history on 2 weekdays and 1 weekend day before and again during the 4 weeks of the study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Reduced Fat Vegan Diet | Active Comparator | Plant based diet with as few added oils and fats as possible. |
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| American Heart Association Diet | Active Comparator | Diet emphasizing fruits, vegetables and whole grains but also low fat dairy, low fat meat and fish. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| American Heart Association Diet | Other |
| ||
| Reduced Fat Vegan Diet |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Body Mass Index BMI Percentile | baseline, 4 weeks | |
| Children Change in BMI Z Score | Body mass index z-scores, also called BMI standard deviation (s.d.) scores, are measures of relative weight adjusted for child age and sex. Given a child's age, sex, BMI, and an appropriate reference standard, a BMI z-score (or its equivalent BMI-for-age percentile) can be determined. Negative BMI z-scores indicate a BMI that is lower than the population mean, while positive BMI scores indicate a value that is higher than the population mean. A decrease in the BMI z-score over time indicate a lowering of the BMI. Z-scores of 1.03 and 1.64 correspond to the 85th and 95th percentiles of BMI-for-age, which are the definitions of overweight and obesity in children. | baseline, 4 weeks |
| Change in Blood Pressure (BP) | baseline, 4 weeks | |
| Change in Weight | baseline, 4 weeks | |
| Change in Circumference | baseline, 4 weeks | |
| Change in PAQ (Physical Activity Questionnaire) | PAQ self reported questions based on activity level from 1 (low activity) to 5 (high activity), overall PAQ score is a mean of the questions. | baseline, 4 weeks |
| Change in Lipid Profile | baseline, 4 weeks | |
| Change in Glucose | baseline, 4 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| PB/AHA - Adjusted Mean Difference BMI | Baseline, 4 weeks | |
| PB/AHA - Adjusted Mean Difference BMI Z Score Children | Baseline, 4 weeks | |
| PB/AHA - Adjusted Mean BP |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Michael Macknin, MD | The Cleveland Clinic | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Cleveland Clinic | Cleveland | Ohio | 44195 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22084329 | Background | Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents; National Heart, Lung, and Blood Institute. Expert panel on integrated guidelines for cardiovascular health and risk reduction in children and adolescents: summary report. Pediatrics. 2011 Dec;128 Suppl 5(Suppl 5):S213-56. doi: 10.1542/peds.2009-2107C. Epub 2011 Nov 14. No abstract available. | |
| 22912422 |
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| ID | Title | Description |
|---|---|---|
| FG000 | Reduced Fat Vegan Diet | Plant based diet with as few added oils and fats as possible. Reduced Fat Vegan Diet |
| FG001 | American Heart Association Diet | Diet emphasizing fruits, vegetables and whole grains but also low fat dairy, low fat meat and fish. American Heart Association Diet |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Other |
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| Change in hsCRP (High-sensitivity C-reactive Protein) | baseline, 4 weeks |
| Change in Liver Enzymes | baseline, 4 weeks |
| Change in IL-6 (Interleukin-6) | baseline, 4 weeks |
| Change in MPO (Myeloperoxidase) | baseline, 4 weeks |
| Change in HgbA1c (Hemoglobin A1c) | baseline, 4 weeks |
| Change in Insulin | baseline, 4 weeks |
| Baseline, 4 weeks |
| PB/AHA - Adjusted Mean Difference Weight | Baseline, 4 weeks |
| PB/AHA - Adjusted Mean Difference Circumference | Baseline, 4 weeks |
| PB/AHA - Adjusted Mean Difference PAQ Children | PAQ self reported questions based on activity level from 1 (low activity) to 5 (high activity), overall PAQ score is a mean of the questions. | Baseline, 4 weeks |
| PB/AHA - Adjusted Mean Lipid Profile | Baseline, 4 weeks |
| PB/AHA - Adjusted Mean Ratio Glucose | Baseline, 4 weeks |
| PB/AHA - Adjusted Mean Ratio hsCRP | Baseline, 4 weeks |
| PB/AHA - Adjusted Mean Ratio Liver Enzymes | Baseline, 4 weeks |
| PB/AHA - Adjusted Mean Ratio IL-6 | Baseline, 4 weeks |
| PB/AHA - Adjusted Mean Ratio MPO | Baseline, 4 weeks |
| PB/AHA - Adjusted Mean Ratio HgbA1c | Baseline, 4 weeks |
| PB/AHA - Adjusted Mean Ratio Insulin | Baseline, 4 weeks |
| Background |
| Olza J, Aguilera CM, Gil-Campos M, Leis R, Bueno G, Martinez-Jimenez MD, Valle M, Canete R, Tojo R, Moreno LA, Gil A. Myeloperoxidase is an early biomarker of inflammation and cardiovascular risk in prepubertal obese children. Diabetes Care. 2012 Nov;35(11):2373-6. doi: 10.2337/dc12-0614. Epub 2012 Aug 21. |
| 19081093 | Background | Pignatelli P, Loffredo L, Martino F, Catasca E, Carnevale R, Zanoni C, Del Ben M, Antonini R, Basili S, Violi F. Myeloperoxidase overexpression in children with hypercholesterolemia. Atherosclerosis. 2009 Jul;205(1):239-43. doi: 10.1016/j.atherosclerosis.2008.10.025. Epub 2008 Nov 6. |
| 21475195 | Background | Wang Z, Klipfell E, Bennett BJ, Koeth R, Levison BS, Dugar B, Feldstein AE, Britt EB, Fu X, Chung YM, Wu Y, Schauer P, Smith JD, Allayee H, Tang WH, DiDonato JA, Lusis AJ, Hazen SL. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature. 2011 Apr 7;472(7341):57-63. doi: 10.1038/nature09922. |
| 19477356 | Background | Tang WH, Wang Z, Cho L, Brennan DM, Hazen SL. Diminished global arginine bioavailability and increased arginine catabolism as metabolic profile of increased cardiovascular risk. J Am Coll Cardiol. 2009 Jun 2;53(22):2061-7. doi: 10.1016/j.jacc.2009.02.036. |
| 19542023 | Background | Wang Z, Tang WH, Cho L, Brennan DM, Hazen SL. Targeted metabolomic evaluation of arginine methylation and cardiovascular risks: potential mechanisms beyond nitric oxide synthase inhibition. Arterioscler Thromb Vasc Biol. 2009 Sep;29(9):1383-91. doi: 10.1161/ATVBAHA.109.185645. Epub 2009 Jun 18. |
| 18349088 | Background | Bhattacharyya T, Nicholls SJ, Topol EJ, Zhang R, Yang X, Schmitt D, Fu X, Shao M, Brennan DM, Ellis SG, Brennan ML, Allayee H, Lusis AJ, Hazen SL. Relationship of paraoxonase 1 (PON1) gene polymorphisms and functional activity with systemic oxidative stress and cardiovascular risk. JAMA. 2008 Mar 19;299(11):1265-76. doi: 10.1001/jama.299.11.1265. |
| 23019600 | Background | Zhang ZJ. Systematic review on the association between F2-isoprostanes and cardiovascular disease. Ann Clin Biochem. 2013 Mar;50(Pt 2):108-14. doi: 10.1258/acb.2012.011263. Epub 2012 Sep 27. |
| 11124751 | Background | Fung TT, Rimm EB, Spiegelman D, Rifai N, Tofler GH, Willett WC, Hu FB. Association between dietary patterns and plasma biomarkers of obesity and cardiovascular disease risk. Am J Clin Nutr. 2001 Jan;73(1):61-7. doi: 10.1093/ajcn/73.1.61. |
| 19321559 | Background | Newby PK. Plant foods and plant-based diets: protective against childhood obesity? Am J Clin Nutr. 2009 May;89(5):1572S-1587S. doi: 10.3945/ajcn.2009.26736G. Epub 2009 Mar 25. |
| 17890496 | Background | Turner-McGrievy GM, Barnard ND, Scialli AR. A two-year randomized weight loss trial comparing a vegan diet to a more moderate low-fat diet. Obesity (Silver Spring). 2007 Sep;15(9):2276-81. doi: 10.1038/oby.2007.270. |
| 12936948 | Background | Hu FB. Plant-based foods and prevention of cardiovascular disease: an overview. Am J Clin Nutr. 2003 Sep;78(3 Suppl):544S-551S. doi: 10.1093/ajcn/78.3.544S. |
| 9863851 | Background | Ornish D, Scherwitz LW, Billings JH, Brown SE, Gould KL, Merritt TA, Sparler S, Armstrong WT, Ports TA, Kirkeeide RL, Hogeboom C, Brand RJ. Intensive lifestyle changes for reversal of coronary heart disease. JAMA. 1998 Dec 16;280(23):2001-7. doi: 10.1001/jama.280.23.2001. |
| 18497261 | Background | Ley RE, Hamady M, Lozupone C, Turnbaugh PJ, Ramey RR, Bircher JS, Schlegel ML, Tucker TA, Schrenzel MD, Knight R, Gordon JI. Evolution of mammals and their gut microbes. Science. 2008 Jun 20;320(5883):1647-51. doi: 10.1126/science.1155725. Epub 2008 May 22. |
| 21596990 | Background | Muegge BD, Kuczynski J, Knights D, Clemente JC, Gonzalez A, Fontana L, Henrissat B, Knight R, Gordon JI. Diet drives convergence in gut microbiome functions across mammalian phylogeny and within humans. Science. 2011 May 20;332(6032):970-4. doi: 10.1126/science.1198719. |
| 21811294 | Background | Zimmer J, Lange B, Frick JS, Sauer H, Zimmermann K, Schwiertz A, Rusch K, Klosterhalfen S, Enck P. A vegan or vegetarian diet substantially alters the human colonic faecal microbiota. Eur J Clin Nutr. 2012 Jan;66(1):53-60. doi: 10.1038/ejcn.2011.141. Epub 2011 Aug 3. |
| 19321569 | Background | Fraser GE. Vegetarian diets: what do we know of their effects on common chronic diseases? Am J Clin Nutr. 2009 May;89(5):1607S-1612S. doi: 10.3945/ajcn.2009.26736K. Epub 2009 Mar 25. |
| 21475185 | Background | Rak K, Rader DJ. Cardiovascular disease: the diet-microbe morbid union. Nature. 2011 Apr 7;472(7341):40-1. doi: 10.1038/472040a. No abstract available. |
| Background | Esselstyn R. The Engine 2 Diet How It All Began. In Esselstyn R "The Engine 2 Diet". New York, Boston: Wellness Central Hachette Book Group, 2009:15-30 |
| 25684089 | Derived | Macknin M, Kong T, Weier A, Worley S, Tang AS, Alkhouri N, Golubic M. Plant-based, no-added-fat or American Heart Association diets: impact on cardiovascular risk in obese children with hypercholesterolemia and their parents. J Pediatr. 2015 Apr;166(4):953-9.e1-3. doi: 10.1016/j.jpeds.2014.12.058. Epub 2015 Feb 12. |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Reduced Fat Vegan Diet | Plant based diet with as few added oils and fats as possible. Reduced Fat Vegan Diet |
| BG001 | American Heart Association Diet | Diet emphasizing fruits, vegetables and whole grains but also low fat dairy, low fat meat and fish. American Heart Association Diet |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
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| Age, Continuous | Mean | Full Range | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in Body Mass Index BMI Percentile | Children only | Posted | Mean | Standard Deviation | BMI percentile | baseline, 4 weeks |
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| Primary | Children Change in BMI Z Score | Body mass index z-scores, also called BMI standard deviation (s.d.) scores, are measures of relative weight adjusted for child age and sex. Given a child's age, sex, BMI, and an appropriate reference standard, a BMI z-score (or its equivalent BMI-for-age percentile) can be determined. Negative BMI z-scores indicate a BMI that is lower than the population mean, while positive BMI scores indicate a value that is higher than the population mean. A decrease in the BMI z-score over time indicate a lowering of the BMI. Z-scores of 1.03 and 1.64 correspond to the 85th and 95th percentiles of BMI-for-age, which are the definitions of overweight and obesity in children. | Children only | Posted | Mean | Standard Deviation | Z Score | baseline, 4 weeks |
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| Primary | Change in Blood Pressure (BP) | Children and parents | Posted | Mean | Standard Deviation | mm Hg | baseline, 4 weeks |
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| Primary | Change in Weight | Children and parents | Posted | Mean | Standard Deviation | kg | baseline, 4 weeks |
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| Primary | Change in Circumference | Children and parents | Posted | Mean | Standard Deviation | cm | baseline, 4 weeks |
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| Primary | Change in PAQ (Physical Activity Questionnaire) | PAQ self reported questions based on activity level from 1 (low activity) to 5 (high activity), overall PAQ score is a mean of the questions. | Children | Posted | Mean | Standard Deviation | units on a scale | baseline, 4 weeks |
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| Primary | Change in Lipid Profile | Children and Parents | Posted | Mean | Standard Deviation | mg/dL | baseline, 4 weeks |
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| Primary | Change in Glucose | Children and Parents | Posted | Mean | Standard Deviation | mg/dL | baseline, 4 weeks |
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| Primary | Change in hsCRP (High-sensitivity C-reactive Protein) | Children and Parents | Posted | Mean | Standard Deviation | mg/L | baseline, 4 weeks |
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| Primary | Change in Liver Enzymes | Children and Parents | Posted | Mean | Standard Deviation | U/L | baseline, 4 weeks |
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| Primary | Change in IL-6 (Interleukin-6) | Children and Parents | Posted | Mean | Standard Deviation | pg/ml | baseline, 4 weeks |
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| Primary | Change in MPO (Myeloperoxidase) | Children and Parents | Posted | Mean | Standard Deviation | pmol/L | baseline, 4 weeks |
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| Primary | Change in HgbA1c (Hemoglobin A1c) | Children and Parents | Posted | Mean | Standard Deviation | percentage | baseline, 4 weeks |
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| Primary | Change in Insulin | Children and Parents | Posted | Mean | Standard Deviation | uU/ml | baseline, 4 weeks |
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| Secondary | PB/AHA - Adjusted Mean Difference BMI | Children and Parents | Posted | Mean | 95% Confidence Interval | percentile | Baseline, 4 weeks |
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| Secondary | PB/AHA - Adjusted Mean Difference BMI Z Score Children | Children | Posted | Mean | 95% Confidence Interval | Z score | Baseline, 4 weeks |
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| Secondary | PB/AHA - Adjusted Mean BP | Children and parents | Posted | Mean | 95% Confidence Interval | ratio | Baseline, 4 weeks |
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| Secondary | PB/AHA - Adjusted Mean Difference Weight | Children and Parents | Posted | Mean | 95% Confidence Interval | kg | Baseline, 4 weeks |
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| Secondary | PB/AHA - Adjusted Mean Difference Circumference | Children and Parents | Posted | Mean | 95% Confidence Interval | cm | Baseline, 4 weeks |
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| Secondary | PB/AHA - Adjusted Mean Difference PAQ Children | PAQ self reported questions based on activity level from 1 (low activity) to 5 (high activity), overall PAQ score is a mean of the questions. | Children | Posted | Mean | 95% Confidence Interval | units on a scale | Baseline, 4 weeks |
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| Secondary | PB/AHA - Adjusted Mean Lipid Profile | Children and parents | Posted | Mean | 95% Confidence Interval | mg/dL | Baseline, 4 weeks |
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| Secondary | PB/AHA - Adjusted Mean Ratio Glucose | Children and Parents | Posted | Mean | 95% Confidence Interval | ratio | Baseline, 4 weeks |
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| Secondary | PB/AHA - Adjusted Mean Ratio hsCRP | Children and Parents | Posted | Mean | 95% Confidence Interval | ratio | Baseline, 4 weeks |
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| Secondary | PB/AHA - Adjusted Mean Ratio Liver Enzymes | Children and Parents | Posted | Mean | 95% Confidence Interval | ratio | Baseline, 4 weeks |
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| Secondary | PB/AHA - Adjusted Mean Ratio IL-6 | Children and Parents | Posted | Mean | 95% Confidence Interval | ratio | Baseline, 4 weeks |
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| Secondary | PB/AHA - Adjusted Mean Ratio MPO | Children and Parents | Posted | Mean | 95% Confidence Interval | ratio | Baseline, 4 weeks |
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| Secondary | PB/AHA - Adjusted Mean Ratio HgbA1c | Children and Parents | Posted | Mean | 95% Confidence Interval | ratio | Baseline, 4 weeks |
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| Secondary | PB/AHA - Adjusted Mean Ratio Insulin | Children and Parents | Posted | Mean | 95% Confidence Interval | ratio | Baseline, 4 weeks |
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Reduced Fat Vegan Diet | Plant based diet with as few added oils and fats as possible. Reduced Fat Vegan Diet | 0 | 32 | 0 | 32 | ||
| EG001 | American Heart Association Diet | Diet emphasizing fruits, vegetables and whole grains but also low fat dairy, low fat meat and fish. American Heart Association Diet | 0 | 28 | 0 | 28 |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Michael Macknin, MD | Cleveland Clinic | 216 444-5512 | macknim@ccf.org |
| ID | Term |
|---|---|
| D002318 | Cardiovascular Diseases |
| D006937 | Hypercholesterolemia |
| D009765 | Obesity |
| D005234 | Fatty Liver |
| ID | Term |
|---|---|
| D006949 | Hyperlipidemias |
| D050171 | Dyslipidemias |
| D052439 | Lipid Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D050177 | Overweight |
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D001835 | Body Weight |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
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| Parents Change in BMI |
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| Title | Measurements |
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| Children adj mean ratio diastolic BP |
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| parents adj mean ratio systolic BP |
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| parents adj mean ratio diastolic BP |
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| Parents Weight |
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| parents waist circumference |
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| children arm circumference |
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| parents arm circumference |
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