## Protocol Section
### Identification Module
**NCT ID:** NCT05084079

**Brief Title:** Different Initial Insulin Dose Regimens on Time to Achieve Glycemic Targets and Treatment Safety in SIIT

**Official Title:** The Impact of Different Initial Insulin Dose Regimens on Time to Achieve Glycemic Targets and Treatment Safety in Short-term Intensive Insulin Therapy(SIIT)

#### Organization Study ID Info
**ID:** 2021526
#### Organization
**Class:** OTHER
**Full Name:** Sun Yat-sen University
### Status Module
#### Completion Date
**Date:** 2022-10

**Type:** ESTIMATED

#### Expanded Access Info
**Last Known Status:** RECRUITING
#### Last Update Post Date
**Date:** 2021-10-19

**Type:** ACTUAL

**Last Update Submit Date:** 2021-10-08

**Overall Status:** UNKNOWN

#### Primary Completion Date
**Date:** 2022-10

**Type:** ESTIMATED

#### Start Date
**Date:** 2021-11

**Type:** ESTIMATED

**Status Verified Date:** 2021-10

#### Study First Post Date
**Date:** 2021-10-19
**Type:** ACTUAL
**Study First Submit Date:** 2021-09-26
**Study First Submit QC Date:** 2021-10-08
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Sun Yat-sen University

#### Responsible Party

**Investigator Affiliation:** Sun Yat-sen University

**Investigator Full Name:** Yanbing Li

**Investigator Title:** Director of Endocrinology and Metabolism Department

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Is US Export:** False

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** To compare the effects of different initial insulin dose regimens during the short-term insulin intensive treatment on time to glycemic goal, hypoglycemia prevalence, glycemic variability and other safety problems in newly diagnosed type 2 diabetes mellitus(T2DM) patients, in order to investigate the rational of formula based initiation regimen.

**Detailed Description:** Diabetes has become one of the major chronic non-communicable diseases. Its prevalence was rising in these years. Short-term intensive insulin therapy can improve the β-cell function and nearly half of the patients can live with long-term glycemic remission. It has therefore become the recommended treatment for the newly diagnosis T2DM patients with high blood glucose. However, due to the glycemic goal for intensive therapy is strict, it's important to find out a suitable initial insulin regimen for continuous subcutaneous insulin infusion(CSII) with which patients can achieve euglycemia safely, stably and rapidly. In previous study, the investigators found out that the total daily insulin dose at the first day when euglycemia was achieved（TDD-1） was associated with weight, waist circumference, triglycerides and fasting blood glucose levels. According to this, the investigators figured out a formula for estimation of insulin dose for the short-term intensive insulin therapy in patients with newly diagnosed T2DM. However, its feasibility needs to be further verified. Therefore, the investigators conducted this prospective randomized controlled study to compare the effects of different initial insulin dose regimens during the short-term insulin intensive treatment on time to glycemic goal, hypoglycemia prevalence, glycemic variability and other safety problems in newly diagnosed type 2 diabetes patients, in order to investigate the rational of formula based initiation regimen.

### Conditions Module

**Conditions:**

- Diabetes Mellitus

- Diabetes Mellitus, Type 2

- Glucose Metabolism Disorders

- Metabolic Disease

- Endocrine System Diseases

**Keywords:**

- Short-term intensive insulin therapy

- Insulin dose

- Time to glycemic goal

- Hypoglycemic

- Glycemic variability

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 56

**Type:** ESTIMATED

**Phases:**

- PHASE4

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Initial insulin regimen was decided according to the formula developed by the investigators previously.

**Intervention Names:**

- Drug: CSII with formula-based initial insulin regimen

**Label:** Formula-based

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** Initial insulin regimen was decided according to current guidelines.

**Intervention Names:**

- Drug: CSII with weight-based initial insulin regimen

**Label:** Weight-based

**Type:** PLACEBO_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Formula-based

**Description:** Initial total daily insulin dose(TDD) for CSII was calculated with a formula :（estimate TDD-1(eTDD-1) = 0.35× body weight (kg) + 2.05× FPG (mmol/L) + 4.24×triglyceride(mmol/L) + 0.55× waist circumference (cm) - 49.1）, 42% of which was assigned as total basal dose and 58% as total premeal dose, with the pre-meal doses divided into 30:35:35 for breakfast, lunch and dinner.

**Name:** CSII with formula-based initial insulin regimen

**Other Names:**

- Formula-based regimen

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- Weight-based

**Description:** TDD for CSII was started with 0.5 IU/kg, 50% of which was assigned as total basal dose and 50% as total premeal dose, and the total pre-meal dose was divided equally before each meal.

**Name:** CSII with weight-based initial insulin regimen

**Other Names:**

- Weight-based regimen

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** After CSII begin, the time(days) to reach glycemic goal of each patients. The glycemic goal defined as at least six out of eight-point fingertip blood glucose meet the standard that fasting blood glucose(FBG) or non-postprandial blood glucose is between 4.4-6.0 mmol/L and 2h postprandial blood glucose(PBG) is between 4.4-8.0 mmol/L.

**Measure:** The time to glycemic goal

**Time Frame:** 1 year

#### Secondary Outcomes

**Description:** Differences in incidence of hypoglycemia among treatment arms at the end of study.

**Measure:** Incidence of hypoglycemia

**Time Frame:** 1 year

**Description:** Differences in blood glucose fluctuations among treatment arms at the end of study.

**Measure:** Change of blood glucose fluctuations

**Time Frame:** 1 year

**Description:** Differences in β-cell indicators among treatment arms at the end of study.

**Measure:** Change of β cell function

**Time Frame:** 1 year

**Description:** Differences in insulin sensitivity indicators among treatment arms at the end of study.

**Measure:** Change of insulin sensitivity

**Time Frame:** 1 year

**Description:** Differences in insulin dosage among treatment arms at the end of study.

**Measure:** Change of insulin dosage

**Time Frame:** 1 year

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* Newly diagnosed type 2 diabetes (1999 World Health Organization standard);
* Type 2 diabetic patients who have never received any hypoglycemic therapy (including oral hypoglycemic agents, Chinese medicine , and insulin);
* Body mass index (BMI) between 20-35 kg/m2;
* Fasting plasma glucose (FPG) levels between 7.0 -16.7 mmol/L, glycated haemoglobin \>7.0%;
* Willing to receive CSII intensive treatment during hospitalization and monitoring blood glucose 8 times per day.

Exclusion Criteria:

* Type 1 diabetes or special type of diabetes;
* Acute complications of diabetes: ketoacidosis, hyperosmolar coma, lactic acidosis, etc.;
* Severe macrovascular complications: acute cerebral vascular accidents, acute coronary syndromes, peripheral arterial disease requiring vascular intervention or amputees for hospitalization occur within 12 months before selection;
* Severe microvascular complications: proliferative phase retinopathy; urinary albumin excretion rate(AER)\> 300 mg/g or urinary protein Positive, quantitative\> 0.5 g/d; uncontrolled painful diabetic neuropathy and significant diabetic autonomic neuropathy;
* Obvious liver and kidney dysfunction: alanine aminotransferase ≥ 2.5 times the upper limit of normal, total bilirubin ≥ 1.5 times the upper limit of normal, serum creatinine greater than 150 umol/L or creatinine clearance less than 50 mL/min;
* Significant increase in blood pressure: blood pressure continued to be higher than 180/110 mmHg;
* Significant anemia: hemoglobin \<100g /L may require regular blood transfusions;
* Use of drugs that may affect blood glucose during 12 weeks, such as oral/intravenous corticosteroids, growth hormone, estrogen/progestogen, high-dose diuretics, antipsychotics, etc. Low-dose diuretics for antihypertensive purposes (hydrochlorothiazide \<25 mg/d, indapamide ≤ 1.5 mg/d), and physiological quantities of thyroid hormones used for replacement therapy are not limited to this;
* Effects associated with other underlying diseases influenced the observation of blood glucose, such as systemic infection or severe comorbidity, malignancy or chronic diarrhea, uncontrolled endocrine gland function abnormalities, chronic cardiac insufficiency (grade III and above), psychosis, or pregnant;
* The patients does not cooperate, or the investigator judges that it may be difficult to complete the study.

**Maximum Age:** 65 Years

**Minimum Age:** 20 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** 17301500@qq.com

**Name:** Xinwei Huang, MA

**Phone:** +8613480264781

**Role:** CONTACT

**Contact 2:**

**Email:** turkey310@163.com

**Name:** Liehua Liu, PhD

**Phone:** +8613751748843

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Guangzhou

**Contacts:**

***Contact 1:***

- **Email:** easd04lyb@126.com

- **Name:** Yanbing Li, MD,PhD

- **Phone:** 8602087334331

- **Role:** CONTACT

***Contact 2:***

- **Name:** Yanbing Li, MD,PhD

- **Role:** PRINCIPAL_INVESTIGATOR

**Country:** China

**Facility:** endocrinology department of the first affiliated hospital of Sun Yat-sen University

**State:** Guangdong

**Status:** RECRUITING

**Zip:** 510080

#### Overall Officials

**Official 1:**

**Affiliation:** endocrinology department of the first affiliated hospital of Sun Yat-sen University

**Name:** Yanbing Li, MD,PhD

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**IPD Sharing:** UNDECIDED

### References Module

#### References

**Citation:** Liu L, Ke W, Wan X, Zhang P, Cao X, Deng W, Li Y. Insulin requirement profiles of short-term intensive insulin therapy in patients with newly diagnosed type 2 diabetes and its association with long-term glycemic remission. Diabetes Res Clin Pract. 2015 May;108(2):250-7. doi: 10.1016/j.diabres.2015.02.011. Epub 2015 Feb 21.

**PMID:** 25765670

## Derived Section

### Condition Browse Module - Browse Branches

- Abbrev: BC18

- Name: Nutritional and Metabolic Diseases

- Abbrev: BC19

- Name: Gland and Hormone Related Diseases

- Abbrev: All

- Name: All Conditions

### Condition Browse Module - Browse Leaves

- ID: M7115

- Name: Diabetes Mellitus

- Relevance: HIGH

- As Found: Diabetes Mellitus

- ID: M7119

- Name: Diabetes Mellitus, Type 2

- Relevance: HIGH

- As Found: Diabetes Mellitus, Type 2

- ID: M11639

- Name: Metabolic Diseases

- Relevance: HIGH

- As Found: Metabolic Diseases

- ID: M25403

- Name: Glucose Metabolism Disorders

- Relevance: HIGH

- As Found: Glucose Metabolism Disorders

- ID: M7862

- Name: Endocrine System Diseases

- Relevance: HIGH

- As Found: Endocrine System Diseases

### Condition Browse Module - Meshes

- ID: D000003920

- Term: Diabetes Mellitus

- ID: D000003924

- Term: Diabetes Mellitus, Type 2

- ID: D000008659

- Term: Metabolic Diseases

- ID: D000044882

- Term: Glucose Metabolism Disorders

- ID: D000004700

- Term: Endocrine System Diseases

### Intervention Browse Module - Ancestors

- ID: D000007004

- Term: Hypoglycemic Agents

- ID: D000045505

- Term: Physiological Effects of Drugs

### Intervention Browse Module - Browse Branches

- Abbrev: Hypo

- Name: Hypoglycemic Agents

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: Micro

- Name: Micronutrients

### Intervention Browse Module - Browse Leaves

- ID: M10365

- Name: Insulin

- Relevance: HIGH

- As Found: Day 1

- ID: M10054

- Name: Hypoglycemic Agents

- Relevance: LOW

- As Found: Unknown

- ID: M173166

- Name: Insulin, Globin Zinc

- Relevance: HIGH

- As Found: Day 1

- ID: M17768

- Name: Zinc

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000007328

- Term: Insulin

- ID: C000557859

- Term: Insulin, Globin Zinc

### Misc Info Module

- Version Holder: 2024-05-24
