Medically Reproducing Bariatric Surgery (MRB)

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.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Other: OPTIFAST

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.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Greenville, North Carolina, United States, 27834
      • Department of Veteran Affairs, Greenville Health Care Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: OPTIFAST; 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; 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.

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

Collaborators and Investigators

• Sponsor: Moahad S Dar
• Collaborators: Nestlé; East Carolina University; Durham VA Medical Center
• Investigators: Principal Investigator: Moahad Dar, MD, Dept of Veteran Affairs

Publications and helpful links

General Publications

• Craig CL, Marshall AL, Sjostrom M, Bauman AE, Booth ML, Ainsworth BE, Pratt M, Ekelund U, Yngve A, Sallis JF, Oja P. International physical activity questionnaire: 12-country reliability and validity. Med Sci Sports Exerc. 2003 Aug;35(8):1381-95. doi: 10.1249/01.MSS.0000078924.61453.FB.
• Dar MS, Chapman WH 3rd, Pender JR, Drake AJ 3rd, O'Brien K, Tanenberg RJ, Dohm GL, Pories WJ. GLP-1 response to a mixed meal: what happens 10 years after Roux-en-Y gastric bypass (RYGB)? Obes Surg. 2012 Jul;22(7):1077-83. doi: 10.1007/s11695-012-0624-1.
• Engelgau MM, Geiss LS, Saaddine JB, Boyle JP, Benjamin SM, Gregg EW, Tierney EF, Rios-Burrows N, Mokdad AH, Ford ES, Imperatore G, Narayan KM. The evolving diabetes burden in the United States. Ann Intern Med. 2004 Jun 1;140(11):945-50. doi: 10.7326/0003-4819-140-11-200406010-00035.
• Jackness C, Karmally W, Febres G, Conwell IM, Ahmed L, Bessler M, McMahon DJ, Korner J. Very low-calorie diet mimics the early beneficial effect of Roux-en-Y gastric bypass on insulin sensitivity and beta-cell Function in type 2 diabetic patients. Diabetes. 2013 Sep;62(9):3027-32. doi: 10.2337/db12-1762. Epub 2013 Apr 22.
• Kirschner MA, Schneider G, Ertel NH, Gorman J. An eight-year experience with a very-low-calorie formula diet for control of major obesity. Int J Obes. 1988;12(1):69-80.
• Mingrone G, Panunzi S, De Gaetano A, Guidone C, Iaconelli A, Leccesi L, Nanni G, Pomp A, Castagneto M, Ghirlanda G, Rubino F. Bariatric surgery versus conventional medical therapy for type 2 diabetes. N Engl J Med. 2012 Apr 26;366(17):1577-85. doi: 10.1056/NEJMoa1200111. Epub 2012 Mar 26.

Study record dates

Study Major Dates

• Study Start (Actual): January 31, 2018
• Primary Completion (Actual): October 23, 2018
• Study Completion (Actual): October 23, 2018

Study Registration Dates

• First Submitted: July 5, 2017
• First Submitted That Met QC Criteria: July 20, 2017
• First Posted (Actual): July 21, 2017

Study Record Updates

• Last Update Posted (Actual): January 31, 2020
• Last Update Submitted That Met QC Criteria: January 29, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: GLP-1; Liraglutide; Roux-en-y gastric bypass; OPTIFAST
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: 02050

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No