Safety and Efficacy of Long Limb Roux-en Y Reconstruction

Gastric Cancer Clinical Trial

— LoLiRoRe  

Official title:

Long Limb Roux-en Y Reconstruction After Gastrectomy As A Potential Cure for Type 2 Diabetes Mellitus in Non-Obese Gastric Cancer Patients - a Pilot Project to Validate a Prospective Randomized Control Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01373346
• Other study ID #: seungho-1
• Status: Completed
• Phase: N/A
• First received: June 13, 2011
• Last updated: August 30, 2012
• Start date: February 2010
• Est. completion date: January 2012

Study information

• Verified date: August 2012
• Source: Gangnam Severance Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Korea: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

We grafted the concept of metabolic surgery (long limb Roux-en Y reconstruction) into gastric cancer surgery. This study aimed to investigate the safety and efficacy of long limb Roux-en Y reconstruction after gastrectomy in non-obese type II diabetes with gastric cancer.

Description:

Type II diabetes in the world is increasing rapidly, and it is known that patients with type II diabetes with morbid obesity that underwent bariatric surgery have resolution of impaired glucose metabolism.

In Asia, most type II diabetes are not morbidly obese and still, it is controversy whether metabolic surgery is effective or not in non-morbid obese patients. As life expectancy is increased, the number of patients with gastric cancer and T2DM is increased as well.

Recently, we studied the outcome of T2DM after gastrectomy and conventional reconstruction in non-obese gastric cancer patients.(Kim JW et al, World J Gastroenterol 2012;18:49) The study was a large-series retrospective study including about 400 patients and the result regarding DM improvement was not satisfactory. Based on our previous results, it is needed to find more effective way to resolve the type II diabetes in gastrectomized patients with gastric cancer.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: January 2012
• Est. primary completion date: January 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Pathologically confirmed gastric cancer with potentially curable state

• Non-obese (Body mass index: less than 30 kg/m2)

• Have a history of Type 2 DM over 6 months (diagnosed by ADA criteria)

1. HBA1c: more than 6.5 %, or Fasting glucose: more than 126 mg/dl (7.0mmol/L) or 2-h plasma glucose: more than 200mg/dl during an OGTT or classic symptoms of hyperglycemia or hyperglycemic crisis, a random plasma glucose: more than 200mg/dl

2. Anti-GAD antibody (-), Anti-islet antibody (-)

• C-peptide level: above 1ng/ml

Exclusion Criteria:

• Patient who receive non-curative operation

• Patient who have less than one year life expectancy

• Pregnant patient

• Acute inflammation status patient

• Chronic renal disease patient (Serum creatin level: more than 1.5mg/dl)

• Chronic liver disease patient (Serum AST or ALT level: more than twice of upper limit of normal range)

• Have a history of receiving medications such as dipeptidyl peptidase IV(DPP- IV) inhibitor or glucagon like peptide-I (GLP-I) analogue

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus Type 2 in Nonobese
• Diabetes Mellitus, Type 2
• Gastric Cancer
• Stomach Neoplasms

Intervention

Procedure:
• Long limb Roux-en Y reconstruction
After radical gastrectomy, the gastrointestinal tract was reconstructed by Roux-en-Y gastrojejunostomy or esophagojejunostomy. The jejunum was divided at approximately 100-120 cm distal to the ligament of Treitz and the distal limb of the jejunum was then anastomosed along the proximal gastric greater curvature or esophagus. The jejuno-jejunostomy was performed approximately 100 to 120 cm distal from the gastrojejunal or esophagojejunal anastomosis

Locations

Country	Name	City	State
Korea, Republic of	GangNam Severance Hospital	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Gangnam Severance Hospital

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (18)

ANGERVALL L, DOTEVALL G, TILLANDER H. Amelioration of diabetes mellitus following gastric resection. Acta Med Scand. 1961 Jun;169:743-8. — View Citation

Buchwald H, Estok R, Fahrbach K, Banel D, Jensen MD, Pories WJ, Bantle JP, Sledge I. Weight and type 2 diabetes after bariatric surgery: systematic review and meta-analysis. Am J Med. 2009 Mar;122(3):248-256.e5. doi: 10.1016/j.amjmed.2008.09.041. Review. — View Citation

Cohen R, Pinheiro JS, Correa JL, Schiavon CA. Laparoscopic Roux-en-Y gastric bypass for BMI < 35 kg/m(2): a tailored approach. Surg Obes Relat Dis. 2006 May-Jun;2(3):401-4, discussion 404. — View Citation

Cohen RV, Schiavon CA, Pinheiro JS, Correa JL, Rubino F. Duodenal-jejunal bypass for the treatment of type 2 diabetes in patients with body mass index of 22-34 kg/m2: a report of 2 cases. Surg Obes Relat Dis. 2007 Mar-Apr;3(2):195-7. — View Citation

DeFronzo RA, Matsuda M. Reduced time points to calculate the composite index. Diabetes Care. 2010 Jul;33(7):e93. doi: 10.2337/dc10-0646. — View Citation

DePaula AL, Macedo AL, Mota BR, Schraibman V. Laparoscopic ileal interposition associated to a diverted sleeve gastrectomy is an effective operation for the treatment of type 2 diabetes mellitus patients with BMI 21-29. Surg Endosc. 2009 Jun;23(6):1313-20. doi: 10.1007/s00464-008-0156-x. Epub 2008 Oct 2. — View Citation

Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004 Aug;240(2):205-13. — View Citation

Emoto M, Nishizawa Y, Maekawa K, Hiura Y, Kanda H, Kawagishi T, Shoji T, Okuno Y, Morii H. Homeostasis model assessment as a clinical index of insulin resistance in type 2 diabetic patients treated with sulfonylureas. Diabetes Care. 1999 May;22(5):818-22. — View Citation

Frenken M, Cho EY, Karcz WK, Grueneberger J, Kuesters S. Improvement of type 2 diabetes mellitus in obese and non-obese patients after the duodenal switch operation. J Obes. 2011;2011:860169. doi: 10.1155/2011/860169. Epub 2011 Mar 3. — View Citation

FRIEDMAN MN, SANCETTA AJ, MAGOVERN GJ. The amelioration of diabetes mellitus following subtotal gastrectomy. Surg Gynecol Obstet. 1955 Feb;100(2):201-4. — View Citation

Katz A, Nambi SS, Mather K, Baron AD, Follmann DA, Sullivan G, Quon MJ. Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans. J Clin Endocrinol Metab. 2000 Jul;85(7):2402-10. — View Citation

Kim JW, Cheong JH, Hyung WJ, Choi SH, Noh SH. Outcome after gastrectomy in gastric cancer patients with type 2 diabetes. World J Gastroenterol. 2012 Jan 7;18(1):49-54. doi: 10.3748/wjg.v18.i1.49. — View Citation

Navarrete SA, Leyba JL, Llopis SN. Laparoscopic sleeve gastrectomy with duodenojejunal bypass for the treatment of type 2 diabetes in non-obese patients: technique and preliminary results. Obes Surg. 2011 May;21(5):663-7. doi: 10.1007/s11695-011-0371-8. — View Citation

Orci L, Chilcott M, Huber O. Short versus long Roux-limb length in Roux-en-Y gastric bypass surgery for the treatment of morbid and super obesity: a systematic review of the literature. Obes Surg. 2011 Jun;21(6):797-804. doi: 10.1007/s11695-011-0409-y. Review. — View Citation

Pories WJ, Swanson MS, MacDonald KG, Long SB, Morris PG, Brown BM, Barakat HA, deRamon RA, Israel G, Dolezal JM, et al. Who would have thought it? An operation proves to be the most effective therapy for adult-onset diabetes mellitus. Ann Surg. 1995 Sep;222(3):339-50; discussion 350-2. — View Citation

Rubino F, Forgione A, Cummings DE, Vix M, Gnuli D, Mingrone G, Castagneto M, Marescaux J. The mechanism of diabetes control after gastrointestinal bypass surgery reveals a role of the proximal small intestine in the pathophysiology of type 2 diabetes. Ann Surg. 2006 Nov;244(5):741-9. — View Citation

Yang J, Li C, Liu H, Gu H, Chen P, Liu B. Effects of subtotal gastrectomy and Roux-en-Y gastrojejunostomy on the clinical outcome of type 2 diabetes mellitus. J Surg Res. 2010 Nov;164(1):e67-71. doi: 10.1016/j.jss.2010.07.004. Epub 2010 Jul 30. — View Citation

Yoon KH, Lee JH, Kim JW, Cho JH, Choi YH, Ko SH, Zimmet P, Son HY. Epidemic obesity and type 2 diabetes in Asia. Lancet. 2006 Nov 11;368(9548):1681-8. Review. — View Citation

* Note: There are 18 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Morbidity	For the evaluation of safety, morbidity were analyzed. For the evaluation of short-term safety, complications higher than the Clavien-Dindo grade II (Dindo et. Ann Surg 240:205 2004) were collected.; *Clavien-dindo classification of surgical complications Grade II: Requiring pharmacological treatment with drugs other than such allowed for grade I complications. Blood transfusions and total parenteral nutrition are also included.; Grade III: Requiring surgical, endoscopic or radiological intervention Grade IV:Life-threatening complication (including CNS complications)‡ requiring IC/ICU-management Grade V:Death of a patient Suffix'd' : If the patient suffers from a complication at the time of discharge ,the suffix "d" (for 'disability') is added to the respective grade of complication. This label indicates the need for a follow-up to fully evaluate the complication.; For the evaluation of long-term safety, the patients were evaluated every month after discharge.	Until end of study (on average 14.8 months)	Yes
Primary	HbA1c	For the evaluation of efficacy for the operation, HbA1c(%) was measured serially (preop. 6months after op. until end of study(on average 14.8 months)).; HbA1c is formed in a non-enzymatic glycation pathway by hemoglobin's exposure to plasma glucose and measured by high-performance liquid chromatography (HPLC) The HbA1c was calculated as a ratio to total hemoglobin.	Before operation , 6 months after operation, Until end of study (on average 14.8 months)	No
Primary	Hemoglobin	For the evaluation of long-term safety, hemoglobin was measured to determine the degree of anemia and malnutrition.	Before operation , 6 months after operation, Until end of study (on average 14.8 months)	No
Primary	Albumin	For the evaluation of long-term safety, albumin was measured to determine malnutrition.	Before operation , 6 months after operation, Until end of study (on average 14.8 months)	No
Primary	Operation Related Mortality	Operation related mortality was measured for the evaluation of safety for the operation. Operation related mortality was defined as any complication resulting in the death of the patient within 1 month or during hospitalization after operation.	Until end of study (on average 14.8 months)	Yes
Secondary	Matsuda Index	Matsuda Index(Insulin Sensitivity Index) was measured.; The Matsuda index was obtained using the following formula: Matsuda index = 10000/square root of [(fasting glucose × fasting insulin) × (mean glucose × mean insulin during OGTT)]	Before operation , 6 months after operation, Until end of study (on average 14.8 months)	No
Secondary	QUICKI	The quantitative insulin sensitivity check index (QUICKI) was measured.; The QUICKI was obtained using the following formula: 1 / (log(fasting insulin µU/mL) + log(fasting glucose mg/dL))	Before operation , 6 months after operation , Until end of study (on average 14.8 months)	No
Secondary	HOMA-IR	HOMA-IR(Homeostasis model assessment-estimated insulin resistance) was measured.; HOMA-IR was obtained using the following formula: Glucose(mg/dl) x Insulin/405	Before operation , 6 months after operation, Until end of study (on average 14.8 months)	No
Secondary	HOMA-B	HOMA-B(Homoeostasis model assessment-derived beta-cell function) was measured.; HOMA-B was obtained using the following formula: 225 × 18/fasting insulin(mU/L) × fasting glucose(mg/dL)	Before operation , 6 months after operation, Until end of study (on average 14.8 months)	No
Secondary	Body Mass Index	BMI(Body Mass index , kg/?) was measured.; BMI was obtained using the following formula: Weight (kg) / (Height (m) x Height (m))	Before operation, 6 Months After Operation, Until End of Study(on Average 14.8 Months)	No
Secondary	Matsuda Index : Good Response Group	At the end of the study, the follow-up duration was 12.5 ± 5.5 months (6.0 - 21.7 months). Some patients showed normal FPG level and HbA1c < 6% without any antidiabetic medications after operation. We called this group as "good response group". We analyzed the change of insulin sensitivity after operation in good response group.; The Matsuda index(Insulin Sensitivity Index) was obtained using the following formula: Matsuda index = 10000/square root of [(fasting glucose × fasting insulin) × (mean glucose × mean insulin during OGTT)]	Before operation , 6 months after operation, Until end of study (on average 14.8 months)	No
Secondary	QUICKI : Good Response Group	At the end of the study, the follow-up duration was 12.5 ± 5.5 months (6.0 - 21.7 months). Some patients showed normal FPG level and HbA1c < 6% without any antidiabetic medications. We called this group as "good response group". We analyzed the change of insulin sensitivity after operation in good response group. The quantitative insulin sensitivity check index (QUICKI) was measured.; The QUICKI is obtained using the following formula: 1 / (log(fasting insulin µU/mL) + log(fasting glucose mg/dL))	Before operation, 6 months after operation, Until end of study (on average 14.8 months)	No
Secondary	HOMA-IR : Good Response Group	At the end of the study, the follow-up duration was 12.5 ± 5.5 months (6.0 - 21.7 months). Some patients showed normal FPG level and HbA1c < 6% without any antidiabetic medications. We called this group as "good response group". We analyzed the change of insulin resistance after operation in good response group.; HOMA-IR(Homeostasis model assessment-estimated insulin resistance) was measured.; HOMA-IR was obtained using the following formula: Glucose(mg/dl) x Insulin/405	Before operation, 6 months after operation, Until end of study (on average 14.8 months)	No
Secondary	HOMA-B : Good Response Group	At the end of the study, the follow-up duration was 12.5 ± 5.5 months (6.0 - 21.7 months). Some patients showed normal FPG level and HbA1c < 6% without any antidiabetic medications. We called this group as "good response group". We analyzed the change of beta-cell function after operation in good response group. HOMA-B(Homoeostasis model assessment-derived beta-cell function) was measured.; HOMA-B was obtained using the following formula: 225 × 18/fasting insulin(mU/L) × fasting glucose(mg/dL)	Before operation, 6 months after operation, Until end of study (on average 14.8 months)	No
Secondary	Body Mass Index : Good Response Group	At the end of the study, the follow-up duration was 12.5 ± 5.5 months (6.0 - 21.7 months). Some patients showed normal FPG level and HbA1c < 6% without any antidiabetic medications. We called this group as "good response group". We analyzed the change of weight change after operation in good response group.; BMI(Body Mass index , kg/?) was measured.; BMI was obtained using the following formula: Weight (kg) / (Height (m) x Height (m))	Before operation, 6 months after operation, Until end of study (on average 14.8 months)	No
Secondary	HbA1c : Good Response Group	At the end of the study, the follow-up duration was 12.5 ± 5.5 months (6.0 - 21.7 months). Some patients showed normal FPG level and HbA1c < 6% without any antidiabetic medications. We called this group as "good response group". We analyzed the change of HbA1c after operation in good response group.; HbA1c is formed in a non-enzymatic glycation pathway by hemoglobin's exposure to plasma glucose and measured by high-performance liquid chromatography (HPLC); The HbA1c was calculated as a ratio to total hemoglobin.	Before operation, 6 months after operation, Until end of study (on average 14.8 months)	No
Secondary	Hemoglobin : Good Response Group	At the end of the study, the follow-up duration was 12.5 ± 5.5 months (6.0 - 21.7 months). Some patients showed normal FPG level and HbA1c < 6% without any antidiabetic medications. We called this group as "good response group". For the evaluation of long-term safety, hemoglobin was measured to determine the degree of anemia and malnutrition in good response group.	Before operation, 6 months after operation, Until end of study (on average 14.8 months)	No
Secondary	Albumin : Good Response Group	At the end of the study, the follow-up duration was 12.5 ± 5.5 months (6.0 - 21.7 months). Some patients showed normal FPG level and HbA1c < 6% without any antidiabetic medications. We called this group as "good response group". We analyzed the change of albumin level after operation in good response group for the evaluation of long-term safety.	Before operation, 6 months after operation, Until end of study (on average 14.8 months)	No