To Evaluate Clinical Efficacy and Safety of Diabetes-Specific Formula (Nutren Diabetes)

Study Overview
=================
Brief Summary
-----------------
This study has a parallel, non-inferiority design, comparing the 24h AUC of Nutren Diabetes group with Fresubin Diabetes group at 2-4 days since the start of formal intervention.

Detailed Description
-----------------
This is a randomized, active-control, open labelled study in which either Nutren Diabetes or Fresubin Diabetes will be given to patients with diabetes for aound 9 days. 24h AUC, TIR, TBR, prealbumin albumin etc. will be evaluated. And also safety-related laboratory parameters, numbers, severity, outcome of AEs will be evaluated too.

Official Title
-----------------
Clinical Efficacy and Safety of Diabetes-Specific Formula (Nutren Diabetes) for Nutritional Support in Diabetic Patients With Dysphagia

Conditions
-----------------
Diabetes Mellitus

Intervention / Treatment
-----------------
* Dietary Supplement: Nutren Diabetes
* Dietary Supplement: Fresubin Diabetes


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 1. Male or female aged 18-75 years old (inclusive); 2. Diagnosis of diabetes, and stable use of hypoglycemic drugs for about 1 month (refer to Guidelines for the Prevention and Treatment of Type 2 Diabetes Mellitus in China (2020) for the diagnosis of diabetes); 3. Glycosylated hemoglobin (HbA1c) <8.5%; 4. Inability to feed orally; 5. It is estimated that tube feeding would be required for more than 9 days; 6. Patients or their guardians (or authorized personnel) have fully understood the study procedures of this trial and are willing to sign the informed consent form (ICF). Exclusion Criteria: 1. Subjects with congenital metabolism disorder or allergy to any ingredient in the product (such as whey protein, milk protein concentrate, soybean lecithin); those with congenital intolerance to fructose; 2. Patients who are not suitable for enteral nutrition, such as those with active gastrointestinal (GI) hemorrhage, intestinal ischemia, paralytic/mechanical ileus, decreased GI tension, stress ulcer, as well as severe abdominal distension, diarrhea and other digestive and absorptive dysfunction; 3. Subjects with severe local broken skin which affects the use of continuous glucose monitoring (CGM) system; 4. Subjects who have concurrent severe malnutrition (body mass index [BMI] <15), severe hypertriglyceridemia (triglyceride≥5.6 mmol/L), severe hypoproteinemia (albumin<20 g/L), severe immunosuppression (neutrophils<1500/mm3 or lymphocytes<500/mm3), severe anemia (hemoglobin<60 g/L), severe infection, high fever and other stress conditions; 5. Subjects with fasting C-peptide < 100 pmol/L (0.3 ng/mL); 6. Subjects who are receiving intracranial pressure reduction therapy; 7. Patients with active malignant tumor (except for glioma, meningioma) or in the period of radiochemotherapy; 8. Patients with severe cardiac failure (New York Heart Association [NYHA] Class IV); those with severe liver or renal impaired function (glomerular filtration rate < 30 mL/min/1.73 m2, or levels of transaminases or transpeptidases more than 3 times the upper limit of normal); or those with conditions such as active hyperthyroidism, treatment-resistant hypothyroidism; 9. Subjects with one of the following conditions: hemodynamic instability, life-threatening multiple injuries, as well as severe acidosis, shock, sepsis; 10. Recent (within 3 months) acute complications of diabetes, such as diabetic ketoacidosis, hyperosmolar hyperglycemic syndrome; 11. It is expected to perform magnetic resonance imaging during the routine study; 12. Subjects who have used systemic glucocorticoid therapy within 2 weeks prior to screening or are expected to use during the study; 13. Women who are pregnant or plan to become pregnant or are breastfeeding; 14. Life expectancy ≤ 30 days; 15. Participated in other interventional clinical trials within 4 weeks prior to screening, including those involved in drugs, nutritional preparations, medical devices, etc.; 16. Other cases not eligible for this study in the investigator's opinion, such as inflammatory bowel disease (Crohn's disease or ulcerative colitis), acute pancreatitis, unstable vital signs, and if it does, the reasons for ineligibility should be recorded.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nutren Diabetes group<br>Product Replacement phase: 1-5 days, tube-feeding, 25kcal/kg/day Formal intervention phase:7 days, tube-feeding, 25kcal/kg/day | Dietary Supplement: Nutren Diabetes<br>* Product replace phase: 1-5 days, tube feeding, 25kcal/kg/day Formal intervention phase:7 days, tube feeding, 25kcal/kg/day<br>|
| Active Comparator: Fresubin Diabetes group<br>Product Replacement phase: 1-5 days, tube-feeding, 25kcal/kg/day Formal intervention phase:7 days, tube-feeding, 25kcal/kg/day | Dietary Supplement: Fresubin Diabetes<br>* Product replace phase: 1-5 days, tube feeding, 25kcal/kg/day Formal intervention phase:7 days, tube feeding, 25kcal/kg/day<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 24h AUC of Nutren Diabetes group with Fresubin Diabetes group | mean area under the blood glucose concentration-time curve from time 0 to 24h (24h AUC) | 2-4 days since the start of formal intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Coefficient of variation of blood glucose | CV data from CGM | Day 2 upon formal intervention | 
| Time in range | TIR from CGM | Day 2 - 4 upon formal intervention | 
| Time above range | TAR from CGM | Day 2 - 4 upon formal intervention | 
| Time below range | TBR from CGM | Day 2 - 4 upon formal intervention | 
| Mean amplitude of glycemic excursion | MAGE from CGM | Day 2 - 4 upon formal intervention | 
| Peak blood glucose | Peak blood from CGM | Day 4 upon formal intervention | 
| Fasting plasma glucose | FPG from laboratory test | Day 7 upon formal intervention | 
| Prealbumin | Prealbumin from laboratory test | Day 7 upon formal intervention | 
| Albumin | Albumin from laboratory test | Day 7 upon formal intervention |