Medically Reproducing Bariatric Surgery

NCT03225209 | Completed Phase 2 FDA Drug

• 1 other identifier: 02050
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

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.

Conditions

Type 2 Diabetes Mellitus

Keywords

Roux-en-y gastric bypass; GLP-1; Liraglutide; OPTIFAST

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Change in Weight

  Change in weight in kilograms from baseline at week 12 and week 24 will be measured

• Change in Medication intensity

  Change in MES from baseline at week 12 and week 24 will be measured

• Change in Health Related Quality of Life (HRQOL)

  Change in PAID from baseline at week 12, and week 24 will be measured

• Change in Health Related Quality of Life

  Change in EQ-5D-5L from baseline at week 12 and week 24 will be measured

• Change in Physical activity

  Change in IPAQ from baseline at week 12 and week 24 will be measured

Study Arms (1)

OPTIFAST

EXPERIMENTAL

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

Interventions

OPTIFAST OTHER

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.

OPTIFAST

Eligibility Criteria

• Age: 25 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Moahad S Dar: lead
• Société des Produits Nestlé (SPN): collaborator
• Durham VA Medical Center: collaborator
• East Carolina University: collaborator

Study Sites (1)

Department of Veteran Affairs, Greenville Health Care Center

Greenville, North Carolina, 27834, United States

Location

Related Publications (6)

• 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.

  PMID: 12900694 BACKGROUND

• 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.

  PMID: 22419108 BACKGROUND

• 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.

  PMID: 15172919 BACKGROUND

• 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.

  PMID: 23610060 BACKGROUND

• 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.

  PMID: 3360564 BACKGROUND

• 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.

  PMID: 22449317 BACKGROUND

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Moahad Dar, MD

  Dept of Veteran Affairs

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Model Details: "Proof of concept" study

Study Record Dates

• First Submitted: July 5, 2017
• First Posted: July 21, 2017
• Study Start: January 31, 2018
• Primary Completion: October 23, 2018
• Study Completion: October 23, 2018
• Last Updated: January 31, 2020

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)