The Medically Reproducing Bariatric Surgery (MRB) II Study

NCT06363747 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: 123456
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

Roux-en-Y (RYGB) gastric bypass reduces the size and capacity of the stomach and bypasses a portion of the small intestine which leads to decreased food intake and higher levels of a gut hormone called GLP-1 (glucagon-like-peptide-1). These changes lead to weight loss, improved blood sugars and often remission of type 2 diabetes but most patients do not qualify or want surgery. The investigators are searching for ways to make the beneficial effects of RYGB available to most type 2 diabetes patients rather than a select few that undergo RYGB. The investigators believe that parts of RYGB can be medically reproduced through a combination of diet and medicine. Once weekly injectable GLP-1 medicine that leads to weight loss and improved blood sugar control in type 2 diabetes are now FDA approved. Optifast is a medically supervised diet that safely reduces calorie intake to 800 calories per day for three months by replacing normal meals with specially prepared bars and shakes which leads to weight loss and improved blood sugar control in type 2 diabetes. Normal meals are then gradually reintroduced over 6 weeks and the bars/shakes are stopped. The investigators hypothesize that Optifast (diet) + once weekly GLP-1 will lead to weight loss and improvement in blood sugar control in type 2 diabetes similar to what is seen after RYGB.

Conditions

Type 2 Diabetes; Obesity

Keywords

Optifast; Type 2 diabetes; Semglutide

Outcome Measures

Primary Outcomes (1)

• Glycemic Control

  Hemoglobin A1C

  baseline, week 12, week 24, week 48

Secondary Outcomes (3)

• Weight lost

  baseline, week 12, week 24, week 48

• Medication Intensity

  baseline, week 12, week 24, week 48

• Health Related Quality of Life

  baseline, week 12, week 24, week 48

Other Outcomes (1)

• Symptom Item Checklist

  2 week run-in phase

Study Arms (2)

Standard of Care

NO INTERVENTION

Patients in the control group will attend four in-person visits with the study coordinator at baseline, week 12, week 24, and week 48 to measure study outcomes. Patients will get medical drug management (endocrinologist), nutritional/behavioral counseling (dietician, psychologist) and will be maintained on once weekly GLP-1 agonist +/- other diabetic medicines.

Very Low Calorie Diet

EXPERIMENTAL

Patients in the experimental group will attend 4 in-person visits with the study coordinator at baseline, week 12, week 24, and week 48 to measure study outcomes. Additionally, they will undergo a 2 week run-in phase before baseline with weekly meetings to ensure that they are able to tolerate and comply with Optifast. Patients will get medical drug management (endocrinologist), nutritional/behavioral counseling (dietician, psychologist) and will be maintained on Optifast + once weekly GLP-1 agonist +/- other diabetic medicines.

Other: Very Low Calorie Diet

Interventions

Very Low Calorie Diet OTHER

Optifast is a medically supervised very low-calorie diet (VLCD) diet that safely induces caloric restriction

Also known as: Optifast

Very Low Calorie Diet

Eligibility Criteria

• Age: 25 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• male or female
• age 25-75 years
• BMI \>27
• diagnosis of type 2 diabetes
• weight stable for 1 month
• hemoglobin A1C \>7.0%
• on stable dose of once weekly GLP-1 agonist
• on oral or injectable DM2 medicines
• interested in losing weight
• agreeable to regular visits per study protocol
• access to telephone and reliable transportation and has a VAMC provider
• using a Freestyle Libre glucose monitoring device and/or glucometer device

You may not qualify if:

• age \>75,
• A1C \<7%
• pregnant
• breast feeding
• prior history of pancreatitis
• prior history of gastroparesis
• history of thyroid cancer/multiple endocrine neoplasia/thyroid nodules/medullary thyroid cancer (contraindication to Liraglutide)
• history of gallstones
• history of hyperoxaluria or calcium oxalate nephrolithiasis
• history of Roux-en-Y gastric bypass or gastric sleeve or any other bariatric procedure,
• type 1 diabetes
• any abnormality on the screening EKG that could subject patient to increased risk during the study
• any gastrointestinal condition causing malabsorption (including but not limited to inflammatory bowel disease, celiac sprue)
• unwilling or unable to complete scheduled testing
• any serious and/or unstable medical, psychiatric, or other condition(s) that prevents the patient from providing informed consent or complying with the study

Sponsors & Collaborators

• Durham VA Medical Center: lead
• Société des Produits Nestlé (SPN): collaborator

Study Sites (1)

Greenville VA Health Care Center

Greenville, North Carolina, 27834, United States

Location

Related Publications (28)

• Andreadis P, Karagiannis T, Malandris K, Avgerinos I, Liakos A, Manolopoulos A, Bekiari E, Matthews DR, Tsapas A. Semaglutide for type 2 diabetes mellitus: A systematic review and meta-analysis. Diabetes Obes Metab. 2018 Sep;20(9):2255-2263. doi: 10.1111/dom.13361. Epub 2018 Jun 10.

  PMID: 29756388 BACKGROUND

• Ard JD, Lewis KH, Rothberg A, Auriemma A, Coburn SL, Cohen SS, Loper J, Matarese L, Pories WJ, Periman S. Effectiveness of a Total Meal Replacement Program (OPTIFAST Program) on Weight Loss: Results from the OPTIWIN Study. Obesity (Silver Spring). 2019 Jan;27(1):22-29. doi: 10.1002/oby.22303. Epub 2018 Nov 13.

  PMID: 30421863 BACKGROUND

• Bianciardi E, Gentileschi P, Niolu C, Innamorati M, Fabbricatore M, Contini LM, Procenesi L, Siracusano A, Imperatori C. Assessing psychopathology in bariatric surgery candidates: discriminant validity of the SCL-90-R and SCL-K-9 in a large sample of patients. Eat Weight Disord. 2021 Oct;26(7):2211-2218. doi: 10.1007/s40519-020-01068-2. Epub 2020 Nov 23.

  PMID: 33226607 BACKGROUND

• Chaudhry ZW, Doshi RS, Mehta AK, Jacobs DK, Vakil RM, Lee CJ, Bleich SN, Kalyani RR, Clark JM, Gudzune KA. A systematic review of commercial weight loss programmes' effect on glycemic outcomes among overweight and obese adults with and without type 2 diabetes mellitus. Obes Rev. 2016 Aug;17(8):758-69. doi: 10.1111/obr.12423. Epub 2016 May 26.

  PMID: 27230990 BACKGROUND

• 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

• Diamant M, Nauck MA, Shaginian R, Malone JK, Cleall S, Reaney M, de Vries D, Hoogwerf BJ, MacConell L, Wolffenbuttel BH; 4B Study Group. Glucagon-like peptide 1 receptor agonist or bolus insulin with optimized basal insulin in type 2 diabetes. Diabetes Care. 2014 Oct;37(10):2763-73. doi: 10.2337/dc14-0876. Epub 2014 Jul 10.

  PMID: 25011946 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

• Flegal KM, Carroll MD, Ogden CL, Curtin LR. Prevalence and trends in obesity among US adults, 1999-2008. JAMA. 2010 Jan 20;303(3):235-41. doi: 10.1001/jama.2009.2014. Epub 2010 Jan 13.

  PMID: 20071471 BACKGROUND

• Henry RR, Scheaffer L, Olefsky JM. Glycemic effects of intensive caloric restriction and isocaloric refeeding in noninsulin-dependent diabetes mellitus. J Clin Endocrinol Metab. 1985 Nov;61(5):917-25. doi: 10.1210/jcem-61-5-917.

  PMID: 4044780 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

• Lingvay I, Guth E, Islam A, Livingston E. Rapid improvement in diabetes after gastric bypass surgery: is it the diet or surgery? Diabetes Care. 2013 Sep;36(9):2741-7. doi: 10.2337/dc12-2316. Epub 2013 Mar 25.

  PMID: 23530013 BACKGROUND

• Maney M, Tseng CL, Safford MM, Miller DR, Pogach LM. Impact of self-reported patient characteristics upon assessment of glycemic control in the Veterans Health Administration. Diabetes Care. 2007 Feb;30(2):245-51. doi: 10.2337/dc06-0771.

  PMID: 17259489 BACKGROUND

• Mann DM, Woodward M, Ye F, Krousel-Wood M, Muntner P. Trends in medication use among US adults with diabetes mellitus: glycemic control at the expense of controlling cardiovascular risk factors. Arch Intern Med. 2009 Oct 12;169(18):1718-20. doi: 10.1001/archinternmed.2009.296. No abstract available.

  PMID: 19822830 BACKGROUND

• Mayer SB, Jeffreys AS, Olsen MK, McDuffie JR, Feinglos MN, Yancy WS Jr. Two diets with different haemoglobin A1c and antiglycaemic medication effects despite similar weight loss in type 2 diabetes. Diabetes Obes Metab. 2014 Jan;16(1):90-3. doi: 10.1111/dom.12191. Epub 2013 Aug 29.

  PMID: 23911112 BACKGROUND

• Marso SP, Daniels GH, Brown-Frandsen K, Kristensen P, Mann JF, Nauck MA, Nissen SE, Pocock S, Poulter NR, Ravn LS, Steinberg WM, Stockner M, Zinman B, Bergenstal RM, Buse JB; LEADER Steering Committee; LEADER Trial Investigators. Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med. 2016 Jul 28;375(4):311-22. doi: 10.1056/NEJMoa1603827. Epub 2016 Jun 13.

  PMID: 27295427 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

• Nathan DM, Buse JB, Davidson MB, Ferrannini E, Holman RR, Sherwin R, Zinman B; American Diabetes Association; European Association for Study of Diabetes. Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2009 Jan;32(1):193-203. doi: 10.2337/dc08-9025. Epub 2008 Oct 22.

  PMID: 18945920 BACKGROUND

• Pickard AS, De Leon MC, Kohlmann T, Cella D, Rosenbloom S. Psychometric comparison of the standard EQ-5D to a 5 level version in cancer patients. Med Care. 2007 Mar;45(3):259-63. doi: 10.1097/01.mlr.0000254515.63841.81.

  PMID: 17304084 BACKGROUND

• Ransom D, Ashton K, Windover A, Heinberg L. Internal consistency and validity assessment of SCL-90-R for bariatric surgery candidates. Surg Obes Relat Dis. 2010 Nov-Dec;6(6):622-7. doi: 10.1016/j.soard.2010.02.039. Epub 2010 Feb 23.

  PMID: 20627709 BACKGROUND

• Schofield CJ, Sutherland C. Disordered insulin secretion in the development of insulin resistance and Type 2 diabetes. Diabet Med. 2012 Aug;29(8):972-9. doi: 10.1111/j.1464-5491.2012.03655.x.

  PMID: 22443306 BACKGROUND

• Sobutay E, Bilgic C, Uymaz DS, Sahin B, Mercan S, Kabaoglu B, Yapici Eser H, Yavuz Y. Can We Benefit from the Preoperative Psychometric Test with Symptom Checklist-90-Revised (SCL-90-R) to Predict Weight Loss After Sleeve Gastrectomy? Obes Surg. 2022 May;32(5):1531-1538. doi: 10.1007/s11695-022-05951-y. Epub 2022 Feb 11.

  PMID: 35146601 BACKGROUND

• Stratton IM, Adler AI, Neil HA, Matthews DR, Manley SE, Cull CA, Hadden D, Turner RC, Holman RR. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ. 2000 Aug 12;321(7258):405-12. doi: 10.1136/bmj.321.7258.405.

  PMID: 10938048 BACKGROUND

• Wang Y, Beydoun MA, Liang L, Caballero B, Kumanyika SK. Will all Americans become overweight or obese? estimating the progression and cost of the US obesity epidemic. Obesity (Silver Spring). 2008 Oct;16(10):2323-30. doi: 10.1038/oby.2008.351. Epub 2008 Jul 24.

  PMID: 18719634 BACKGROUND

• Welch GW, Jacobson AM, Polonsky WH. The Problem Areas in Diabetes Scale. An evaluation of its clinical utility. Diabetes Care. 1997 May;20(5):760-6. doi: 10.2337/diacare.20.5.760.

  PMID: 9135939 BACKGROUND

• Haskell WL, Lee IM, Pate RR, Powell KE, Blair SN, Franklin BA, Macera CA, Heath GW, Thompson PD, Bauman A; American College of Sports Medicine; American Heart Association. Physical activity and public health: updated recommendation for adults from the American College of Sports Medicine and the American Heart Association. Circulation. 2007 Aug 28;116(9):1081-93. doi: 10.1161/CIRCULATIONAHA.107.185649. Epub 2007 Aug 1.

  PMID: 17671237 BACKGROUND

• Koepsell TD, Littman AJ, Forsberg CW. Obesity, overweight, and their life course trajectories in veterans and non-veterans. Obesity (Silver Spring). 2012 Feb;20(2):434-9. doi: 10.1038/oby.2011.2. Epub 2011 Feb 3.

  PMID: 21293452 BACKGROUND

Related Links

• SCL-90-R Questionnaire

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Obesity

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Moahad Dar, MD

  Department of Veteran Affairs

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: Control--\[GLP-1 agonist +/- DM2 meds + medical management + nutritional/behavioral counseling\] Experimental---\[Optifast + GLP-1 agonist + medical management + nutritional/behavioral counseling\]

Study Record Dates

• First Submitted: April 9, 2024
• First Posted: April 12, 2024
• Study Start: June 24, 2024
• Primary Completion: November 3, 2025
• Study Completion: November 3, 2025
• Last Updated: February 7, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, CSR
• Time Frame: Study protocol was shared with study sponsor prior to IRB submission. Study sponsor will receive a summary of study results at study conclusion but will not have access to individually identifiable information.

Locations

US (1)