Medically Reproducing Bariatric Surgery

Study Overview
=================
Brief Summary
-----------------
Type 2 diabetes (DM2) is a chronic disease affecting 29 million Americans and a leading cause of blindness, kidney failure, and limb loss (Engelgau et al 2004). Roux-en-Y gastric bypass (RYGB) is the only intervention that leads to durable DM2 remission   80% of the time (Mingrone et al 2012). Yet, it's broad application is limited by cost, invasiveness, and clinical inertia. Medically reproducing RYGB would extend the benefit of disease remission to the vast majority of DM2 patients using a cheaper, less invasive and more palatable treatment approach. Although all of the mechanisms mediating DM2 remission are not known, it is widely accepted that RYGB induces caloric restriction and enhances meal-stimulated release of a gut-peptide called glucagon-like-peptide-1 (GLP-1) both of which improve glycemic control in type 2 diabetes (Dar et al 2012; Jackness 2013). Caloric restriction can be achieved using OPTIFAST which is a commercially available medical weight loss program that has demonstrated the ability to decrease weight and improve glycemic control (Kirschner et al; 1998). Enhanced meal-stimulated GLP-1 release can be achieved using Liraglutide an FDA-approved once daily GLP-1 analogue that improves glycemic control and induces weight loss. The investigators hypothesize that adding OPTIFAST (caloric restriction) in suboptimally controlled DM2 patients on Liraglutide (enhanced meal stimulated GLP-1 release), Metformin and Lantus insulin will medically reproduce RYGB and lead to DM2 remission, weight loss, decreased medication intensity and improved health related quality of life.

Detailed Description
-----------------
This is a 24 week proof of concept study that will examine if adding caloric restriction (OPTIFAST) to enhanced GLP-1 release (Liraglutide) will lead to discontinuation of Lantus and Metformin. The primary outcome measure is change in glycemic control measured as hemoglobin A1C. Secondary outcome measures are change in weight, medication intensity and health related quality of life.

Official Title
-----------------
Medically Reproducing Bariatric Surgery

Conditions
-----------------
Type 2 Diabetes Mellitus

Intervention / Treatment
-----------------
* Other: OPTIFAST


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: male or female age 25-70 years BMI > 30 diagnosis of type 2 diabetes weight stable for 3 months hemoglobin A1C >7% and <10% on Liraglutide on Metformin on Lantus interested in losing weight agreeable to regular visits per study protocol access to telephone and reliable transportation has a VAMC provider Exclusion Criteria: age >70 A1C <7% or >10% current use of prandial insulin current use of sulfonylurea or any other oral agent except for Metformin current sue of any other basal insulin except for Lantus pregnant breast feeding prior history of pancreatitis prior history of gastroparesis history of thyroid cancer/multiple endocrine neoplasia/thyroid nodules/medullary thyroid cancer history of gallstones history of hyperoxaluria or calcium oxalate nephrolithiasis AST/ALT > 2 times the upper limit of normal current or past history of liver disease history of Roux-en-Y gastric bypass or gastric sleeve or any other bariatric procedure type 1 diabetes any gastrointestinal disease causing malabsorption unwilling or unable to complete scheduled testing thiazolidinedione use within past 6 months any serious and/or unstable medical, psychiatric, or other condition(s) that prevents the patient from providing informed consent or complying with the study organ transplantation or those on immunosuppressants chronic anticoagulation recent myocardial infarction, unstable angina, stroke, coronary artery bypass or transient ischemia attacks in the past 6 months chronic prednisone use peptic ulcer disease in past 6 months acute gastrointestinal disorders hepatitis cirrhosis GFR < 50 deep vein thrombosis in the past 6 months bone fractures in the past 6 months lithium use active malignancy substance abuse unstable psychiatric condition history of suicidal ideation enrolled in another research study related to diet and/or physical activity

Ages Eligible for Study
-----------------
Minimum Age: 25 Years
Maximum Age: 70 Years

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

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

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

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Proof of concept study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: OPTIFAST<br>Subjects meeting inclusion criteria will be receive OPTIFAST meal replacement (MR) in the following manner: WK1-WK12 (5 MR/DAY) WK13-14 (4 MR/DAY) WK 15 (3 MR/DAY) WK 16 (2 MR/DAY) WK 17-18 (1 MR/DAY) WK 19-24 (No MR) | Other: OPTIFAST<br>* OPTIFAST meal replacement includes shakes, bars and soups. These meal replacements will completely replace the subject's diet for the first 12 weeks of the study (baseline-week 12) followed by a gradual transition back to prepared meals over 6 weeks (week 13-18). Attempt will be made to reduce or eliminate Lantus and Metformin as long as glycemic control is maintained.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Glycemic control | Hemoglobin A1C (HbA1C) will be used to assess glycemic control during the study | Change in HbA1c from baseline at week 12 and week 24 will be measured | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Weight | Weight in kilograms will be used to assess weight change during the study | Change in weight in kilograms from baseline at week 12 and week 24 will be measured | 
| Change in Medication intensity | Medication effect score (MES) will be used to assess medication intensity during the study | Change in MES from baseline at week 12 and week 24 will be measured | 
| Change in Health Related Quality of Life (HRQOL) | Problem Areas in Diabetes Scale (PAID) is a well-validated measure used in clinical trials regarding diabetes and is a sensitive and specific measure of HRQOL. | Change in PAID from baseline at week 12, and week 24 will be measured | 
| Change in Health Related Quality of Life | EQ-5D-5L is a highly sensitive 5-item health status measure with good performance in Veteran outpatients. It assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. | Change in EQ-5D-5L from baseline at week 12 and week 24 will be measured | 
| Change in Physical activity | International Physical Activity Questionnaire (IPAQ) is a well validated tool to assess daily physical activity | Change in IPAQ from baseline at week 12 and week 24 will be measured | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Roux-en-y gastric bypass, GLP-1, Liraglutide, OPTIFAST