Obesity, Weight Loss, and Cardiovascular Disease Risk

Tracking Information
First Submitted Date ICMJE	September 13, 2005
First Posted Date ICMJE	September 16, 2005
Last Update Posted Date	March 13, 2013
Study Start Date ICMJE	October 2000
Primary Completion Date	Not Provided
Current Primary Outcome Measures ICMJE; (submitted: April 7, 2006)	Weight loss
Original Primary Outcome Measures ICMJE; (submitted: September 13, 2005)	1. Weight loss
Change History	Complete list of historical versions of study NCT00186459 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: April 7, 2006)	Lipid/lipoprotein changes; Blood pressure changes; Insulin resistance changes; Endothelial function changes
Original Secondary Outcome Measures ICMJE; (submitted: September 13, 2005)	1. Lipid/lipoprotein changes; 2. Blood pressure changes; 3. Insulin resistance changes; 4. Endothelial function changes
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Obesity, Weight Loss, and Cardiovascular Disease Risk
Official Title ICMJE	GCRC-CAP-Tracey McLaughlin, MD
Brief Summary	The goal of the study is to define the roles played by resistance to insulin-mediated glucose disposal (insulin resistance) and circulating plasma insulin concentrations in: 1) ability to lose weight; 2) reduction of risk for coronary heart disease as a result of weight loss. We hypothesize that in the setting of caloric restriction, manipulating endogenous insulin concentrations will not alter ability of subjects to lose weight, but will lead to different reduction in CHD risk factors. To test this hypothesis, two parallel studs will be performed. First, obese insulin-resistant individuals will be randomized to one of two equally-hypocaloric diets that vary moderately in proportion of carbohydrate and mono/polyunsaturated fats (lower carbohydrate diet will be associated with greater reduction in endogenous insulin secretion). Second, diabetics treated with insulin secretagogues will be compared to diabetics treated with insulin sensitizers with respect to the same outcomes (secretagogues increase insulin secretion and insulin sensitizers decrease insulin concentrations). Endpoints include weight loss, change in insulin resistance, blood pressure, lipid and lipoproteins, markers of endothelial function, daylong insulin and glucose concentrations: these will be compared, in each of the parallel studies, between the group with insulin-stimulating intervention vs the group with the insulin-sparing intervention.
Detailed Description	While obesity, insulin resistance, and diabetes are highly associated, it is not clear whether insulin resistance and compensatory hyperinsulinemia play important roles in the tendency to gain weight and/or inability to lose weight. The role of hyperinsulinemia in coronary heart disease (CHD)is also unclear. The specific aims of the proposed research are as follows: To compare insulin resistant versus insulin sensitive nondiabetic overweight individuals with respect to their ability to lose weight on a low calorie diet. CHD risk factors before and after weight loss will also be assessed to determine the degree to which insulin resistance is associated with CHD risk, as well as the impact that differences in insulin resistance have on the metabolic benefits of weight loss; To determine if weight loss and its associated metabolic benefits vary as a function of the relative amounts of dietary fat and carbohydrate in hypocaloric diets. Because high carbohydrate diets increase insulin secretion, the relationship between dietary composition and change in circulating insulin concentrations will be analyzed with respect to both weight loss and CHD risk factors.; To quantify and compare the improvement in glycemic control and CHD risk factors associated with weight loss in obese type 2 diabetics, while being treated with 1) an insulin secretagogue (sulfonylurea) or 2) an insulin sensitizer (thiazolidinedione). Manipulation of plasma insulin concentrations with these medications will provide a mechanism by which to evaluate the impact of circulating insulin concentrations on the described outcome measures.; A subgroup of overweight/obese premenopausal women with PCOS will be studied using two diets in crossover design with regard to macronutrient effects on endogenous hyperinsulinism. For this subgroup age range will be 18-50 years, BMI 25-50 kg/m2.; In order to increase our data and therefore increase our better understanding of fat cells and insulin resistance and changes in fat cells with weight loss we would like to increase our participant enrollment to 550 all to be enrolled at Stanford University Medical Center recruiting Bariatric participants: Age for Bariatric patients 30-65 men and women BMI 27-no upper limit Currently we have completed all participants except the bariatric and post bariatric population and those with hypoglycemia following bariatric surgery. The ethnic background of subjects reflects Stanford's patient population.
Study Type ICMJE	Interventional
Study Phase	Not Applicable
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Prevention
Condition ICMJE	Obesity
Intervention ICMJE	Behavioral: Hypocaloric diet of varying macronutrient composition
Study Arms	Not Provided
Publications *	Perelman D, Coghlan N, Lamendola C, Carter S, Abbasi F, McLaughlin T. Substituting poly- and mono-unsaturated fat for dietary carbohydrate reduces hyperinsulinemia in women with polycystic ovary syndrome. Gynecol Endocrinol. 2017 Apr;33(4):324-327. doi: 10.1080/09513590.2016.1259407. Epub 2016 Dec 2.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Unknown status
Estimated Enrollment ICMJE; (submitted: March 12, 2013)	550
Original Enrollment ICMJE; (submitted: September 13, 2005)	180
Study Completion Date	Not Provided
Primary Completion Date	Not Provided
Eligibility Criteria ICMJE	Inclusion Criteria: BMI 30-35; age 35-65; nondiabetic by fasting plasma glucose concentration; no active major organ diseases; insulin resistant or insulin sensitive Exclusion Criteria: anemia; pregnant; major organ disease; active malignancy; eating disorder; active psychiatric illness; chronic inflammatory conditions
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years to 65 Years (Adult)
Accepts Healthy Volunteers	Yes
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT00186459
Other Study ID Numbers ICMJE	RR16071-01
Has Data Monitoring Committee	Not Provided
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Tracey McLaughlin, Stanford University
Study Sponsor ICMJE	Stanford University
Collaborators ICMJE	Not Provided
Investigators ICMJE	Principal Investigator: Dr Tracey Lynn McLaughlin Stanford University
PRS Account	Stanford University
Verification Date	March 2013
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP