Progressive Weight Loss and Metabolic Health

Study Overview
=================
Brief Summary
-----------------
This study will evaluate the potential beneficial cardiometabolic effect of moderate (5%) weight loss and progressive (5%, 10%, and 15%) weight loss in obese adults without diabetes. Participants will be randomly assigned to one of 2 groups. Group 1: supervised weight loss group (low-calorie diet). Group 2: supervised weight maintenance group (normal diet). Of those assigned to group 1, half of the participants will lose 5% of their body weight and the other half will lose 5%, 10%, and 15% of their weight over time under the guidance of a dietitian. Research testing will be repeated at each time point (5%, 10%, and 15% weight loss). In group 2, research testing will be repeated after six months.

Official Title
-----------------
Progressive Weight Loss and Metabolic Health

Conditions
-----------------
Insulin Resistance, Obesity

Intervention / Treatment
-----------------
* Behavioral: Weight Maintenance
* Behavioral: Weight Loss


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Obese: Body Mass Index from 30 to 45 Insulin Resistant: HOMA-IR score greater than or equal to 2 Exclusion Criteria: diabetes smoking pregnancy breastfeeding heart failure history of liver disease including hepatitis alcoholism exercise more than 2 hours per week

Ages Eligible for Study
-----------------
Minimum Age: 21 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Weight Loss<br>Half of the subjects in the weight loss arm will lose 5% of their weight through a low-calorie diet, and half will also lose 10% and 15% body weight. | Behavioral: Weight Loss<br>* Half of the subjects in the weight loss arm will lose 5% of their weight through a low-calorie diet, and half will also lose 10% and 15% body weight.<br>|
| Active Comparator: Weight Maintenance<br>Subjects in the weight maintenance arm will maintain a steady body weight (plus or minus 2% of initial body weight) for six months. | Behavioral: Weight Maintenance<br>* Subjects in the weight maintenance arm will maintain a steady body weight (plus or minus 2% of initial body weight) for six months.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin Sensitivity | In the weight-loss arm we will measure insulin sensitivity at baseline, after 5% weight loss, after 10% weight loss and again after 15% weight loss. Each weight loss phase will last an average of four months for a total of approximately one year. In the weight maintenance arm we will measure insulin sensitivity at baseline and after six months. | baseline through weight loss (approximately one year) | 
| intra-hepatic triglyceride | In the weight-loss arm we will measure intra-hepatic triglyceride at baseline, after 5% weight loss, after 10% weight loss and again after 15% weight loss. Each weight loss phase will last an average of four months for a total of approximately one year. In the weight maintenance arm we will measure intra-hepatic triglyceride at baseline and after six months. | baseline through weight loss (approximately one year) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| total cholesterol | In the weight-loss arm we will measure total cholesterol at baseline, after 5% weight loss, after 10% weight loss and again after 15% weight loss. Each weight loss phase will last an average of four months for a total of approximately one year. In the weight maintenance arm we will measure total cholesterol at baseline and after six months. | baseline through weight loss (approximately one year) | 
| systolic blood pressure | In the weight-loss arm we will measure systolic blood pressure at baseline, after 5% weight loss, after 10% weight loss and again after 15% weight loss. Each weight loss phase will last an average of four months for a total of approximately one year. In the weight maintenance arm we will measure systolic blood pressure at baseline and after six months. | baseline through weight loss (approximately one year) | 
| Cell proliferation (growth) rates in the colon - optional procedure | Colon cell proliferation rates will be determined using stable isotope labelled tracer methods in conjunction with sigmoid colon biopsy samples. In the weight-loss arm we will measure colonocyte proliferation rate at baseline, and once again after weight loss (either 5% weight loss, or 10% weight loss, or 15% weight loss; i.e. only one time after weight loss). Each weight loss phase will last an average of four months for a total of approximately one year. In the weight maintenance arm we will measure colonocyte proliferation rate at baseline and after six months. | baseline through weight loss (approximately four months to one year) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
obesity, weight loss, insulin resistance