Prospective Metabolic Surgery in T2DM Chinese Subjects

Study Overview
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Brief Summary
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The primary goal of this study is to assess impact of metabolic surgery on glycemic control in diabetic patients.

Detailed Description
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The primary objective of this study is to assess the impact of metabolic surgery (Roux-en-Y gastric bypass [RYGB] or sleeve gastrectomy [SG]) on composite measure of glycemic control at 2 years post surgery in a Type 2 Diabetes Mellitus (T2DM) cohort of subjects.

Official Title
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A Prospective, Multi-Center Study for the Evaluation of Metabolic Surgery in Subjects With Type 2 Diabetes in China

Conditions
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Diabetes, Obesity

Intervention / Treatment
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* Procedure: Roux-en-Y gastric bypass
* Procedure: Sleeve gastrectomy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 20 to 60 years of age (inclusive) on the date the informed consent document (ICD) is signed; A body mass index (BMI) from 28 kg/m2 to 50 kg/m2 ; Previously diagnosed for at least 6 months with T2DM according to World Health Organization (WHO) criteria; C-peptide > 1 ng/mL (0.3 nmol/L); Able and willing to comply with procedures required by the protocol; and Able to comprehend and sign or, if illiterate, leave their thumb impression on the study ICD. Exclusion Criteria: History of T2DM for a duration > 10 years; History of drug and/or alcohol abuse within 2 years of Screening Visit; Any previous major GI surgery (e.g., any GI surgery with a resection, etc.). Previous GI surgery allowed include: appendectomy, gall bladder surgery, liver biopsies, and endoscopic procedures; Scheduled concurrent surgical, non-endoscopy, procedure from Visit 1 through the end of Visit 3; Women of childbearing potential who are pregnant or lactating at the time of screening, at the time of surgery, or planning to become pregnant one year or sooner after the surgery; Psychiatric disorders that may affect compliance with the clinical study, including dementia, active psychosis, severe depression, or history of suicide attempts; Any of the following conditions: Inflammatory diseases of the GI tract, including severe intractable esophagitis, gastric ulceration, duodenal ulceration, or specific inflammation such as Crohn's disease or ulcerative colitis that have been active within the past 10 years; End stage renal disease; Abnormal results from glutamic acid decarboxylase autoantibodies (GADA) or protein tyrosine phosphatase-like protein (IA-2A) testing; or Immunocompromised such as that resulting from chronic oral steroid use, cancer chemotherapeutic agents, or immune deficiency disorders; Participation in any other clinical study (not to include registries or survey-only studies) within 30-days or 5 half-lives of an investigational drug (which ever is longer), of Visit 1 (Screening Visit) and for the duration of the study.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Roux-en-Y gastric bypass<br>Subjects who receive a Roux-en-Y gastric bypass | Procedure: Roux-en-Y gastric bypass<br> <br> |
| Active Comparator: Sleeve Gastrectomy<br>Subjects who receive a sleeve gastrectomy | Procedure: Sleeve gastrectomy<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite Measure of Glycemic Control - Complete Remission | Normal measures of glucose metabolism (glycosylated hemoglobin A1c [HbA1c] < 6% [7.0 mmol/L] and fasting plasma glucose [FPG] < 100 mg/dL [5.6 mmol/L]) for 1 year in the absence of antidiabetic medications; | 2 years | 
| Composite Measure of Glycemic Control - Partial remission | Hyperglycemia (HbA1c 6% - 6.4% [7.0 - 7.6 mmol/L] and FPG 100 - 125 mg/dL [5.6 mmol/L - 6.9 mmol/L]) for 1 year in the absence of anti-diabetic medications; | 2 years | 
| Composite Measure of Glycemic Control - Improvement | Significant reduction in HbA1c (by > 1%) or FPG (> 25 mg/dL [1.4 mmol/L]) OR reduction in HbA1c and FPG accompanied by a decrease in antidiabetic medication requirement (by discontinuing insulin or 1 oral agent, or ½ reduction in dose) for at least 1-year duration; | 2 years | 
| Composite Measure of Glycemic Control - Unchanged | The absence of remission or improvement as described earlier; | 2 years | 
| Composite Measure of Glycemic Control - Recurrence | FPG or HbA1c in the diabetic range (≥ 126 mg/dL [7.0 mmol/L] and ≥ 6.5% [7.8 mmol/L], respectively) OR need for antidiabetic medication after initial complete or partial remission. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite Measure of Glycemic Control | The composite measure of glycemic control will be defined as previously described in the primary outcome measure. | 5 years | 
| Evaluation of diabetic nephropathy | Evaluate long-term diabetic nephropathy | 5 years | 
| Evaluation of diabetic retinopathy | Evaluate long-term diabetic retinopathy. | 5 years | 
| Assess changes in HbA1c | Assess changes in HbA1c after the procedure is performed. | 5 years | 
| Assess changes in Weight (kg) | Assess changes in weight after the procedure is performed. | 5 years | 
| Assess changes in BMI | Assess changes in BMI after the procedure is performed. | 5 years | 
| Assess changes in high-density lipoprotein (HDL) (mg/dL and mmol/L) | Assess changes in high-density lipoprotein (HDL) (mg/dL and mmol/L) after the procedure is performed | 5 years | 
| Assess changes in low-density lipoprotein (LDL) (mg/dL and mmol/L | Assess changes in low-density lipoprotein (LDL) (mg/dL and mmol/L) after the procedure is performed. | 5 years | 
| Assess changes in triglycerides (TG) (mg/dL and mmol/L) | Assess changes in triglycerides (TG) (mg/dL and mmol/L) after the procedure is performed. | 5 years | 
| Assess changes in cholesterol (mg/dL and mmol/L) | Assess changes in cholesterol (mg/dL and mmol/L) after the procedure is performed. | 5 years | 
| Assess changes in FPG (mg/dL and mmol/L) | Assess changes in FPG (mg/dL and mmol/L) after the procedure is performed | 5 years | 
| Assess changes in insulin (µU/mL and pmol/L) | Assess changes in insulin (µU/mL and pmol/L) after the procedure is performed | 5 years | 
| Assess changes in serum albumin level (g/L) | Assess changes in serum albumin level (g/L) after the procedure is performed | 5 years | 
| Assess changes in alanine aminotransferase (ALT) level (Unit [U]/L) | Assess changes in alanine aminotransferase (ALT) level (Unit [U]/L) after the procedure is performed | 5 years | 
| Assess changes in aspartate aminotransferase (AST) level (U/L) | Assess changes in aspartate aminotransferase (AST) level (U/L) after the procedure is performed | 5 years | 
| Assess changes in gamma-glutamyl transferase (GGT) level (U/L) | Assess changes in gamma-glutamyl transferase (GGT) level (U/L) after the procedure is performed | 5 years | 
| Assess changes in creatinine levels (mg/dL and mmol/L) | Assess changes in creatinine levels (mg/dL and mmol/L) after the procedure is performed | 5 years | 
| Assess changes in blood urea nitrogen (BUN) levels (mg/dL and mmol/L) | Assess changes in blood urea nitrogen (BUN) levels (mg/dL and mmol/L) after the procedure is performed | 5 years | 
| Assess changes in anti-hypertensive medication | Assess changes in anti-hypertensive medication after the procedure is performed | 5 years | 
| Asses the changes in lipid lowering medication | Asses the changes in lipid lowering medication after the procedure is performed | 5 years | 
| Assess the changes in hyperglycemia medication | Assess the changes in hyperglycemia medication after the procedure is performed | 5 years | 
| Assess the changes in SF-36 Health Survey | Assess the changes in SF-36 Health Survey after the procedure is performed | 5 years |