Obesity, Weight Loss, and Cardiovascular Disease Risk

This study is enrolling participants by invitation only.
Sponsor:
Information provided by (Responsible Party):
Tracey McLaughlin, Stanford University
ClinicalTrials.gov Identifier:
NCT00186459
First received: September 13, 2005
Last updated: March 12, 2013
Last verified: March 2013
  Purpose

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.


Condition Intervention
Obesity
Behavioral: Hypocaloric diet of varying macronutrient composition

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: GCRC-CAP-Tracey McLaughlin, MD

Resource links provided by NLM:


Further study details as provided by Stanford University:

Primary Outcome Measures:
  • Weight loss [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Lipid/lipoprotein changes [ Designated as safety issue: No ]
  • Blood pressure changes [ Designated as safety issue: No ]
  • Insulin resistance changes [ Designated as safety issue: No ]
  • Endothelial function changes [ Designated as safety issue: No ]

Estimated Enrollment: 550
Study Start Date: October 2000
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:

  1. 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
  2. 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.
  3. 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.
  4. 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.
  5. 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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00186459

Locations
United States, California
Stanford University School of Medicine
Stanford, California, United States, 94305
Sponsors and Collaborators
Stanford University
Investigators
Principal Investigator: Dr Tracey Lynn McLaughlin Stanford University
  More Information

No publications provided

Responsible Party: Tracey McLaughlin, Associate Professor, Stanford University
ClinicalTrials.gov Identifier: NCT00186459     History of Changes
Other Study ID Numbers: RR16071-01
Study First Received: September 13, 2005
Last Updated: March 12, 2013
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Cardiovascular Diseases
Obesity
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms

ClinicalTrials.gov processed this record on July 22, 2014