Medically Reproducing Bariatric Surgery

Type 2 Diabetes Mellitus Clinical Trial

— MRB  

Official title:

Medically Reproducing Bariatric Surgery

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03225209
• Other study ID #: 02050
• Status: Completed
• Phase: Phase 2
• Start date: January 31, 2018
• Est. completion date: October 23, 2018

Study information

• Verified date: January 2020
• Source: East Carolina University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 5
• Est. completion date: October 23, 2018
• Est. primary completion date: October 23, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 25 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

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.

Locations

Country	Name	City	State
United States	Department of Veteran Affairs, Greenville Health Care Center	Greenville	North Carolina

Sponsors (4)

Lead Sponsor	Collaborator
Moahad S Dar	Durham VA Medical Center, East Carolina University, Nestlé

Country where clinical trial is conducted

United States, 

References & Publications (6)

Craig CL, Marshall AL, Sjöström 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. — View Citation

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. — View Citation

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. Review. — View Citation

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 ß-cell Function in type 2 diabetic patients. Diabetes. 2013 Sep;62(9):3027-32. doi: 10.2337/db12-1762. Epub 2013 Apr 22. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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