Medically Reproducing Bariatric Surgery (MRB)

Moahad S Dar

Status and phase: Completed; Phase 2

Conditions: Type 2 Diabetes Mellitus

Treatments: Other: OPTIFAST

Study type: Interventional

Funder types: Other; Other U.S. Federal agency; Industry

Identifiers

NCT03225209

02050

Details and patient eligibility

About

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.

Full 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.

Enrollment: 5 patients

Sex: All

Ages: 25 to 70 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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5 participants in 1 patient group

OPTIFAST

Experimental group

Description:

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)

Treatment:

Other: OPTIFAST