- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05284344
The Impact of Glucotoxicity on Gastric Emptying in Chinese Patients With Newly Diagnosed Type 2 Diabetes
Gastric emptying is now recognized as a major determinant of the blood glucose response to carbohydrate in both health and type 2 diabetes (T2D). While patients with longstanding diabetes exhibit a high prevalence of delayed gastric emptying, i.e. gastroparesis, patients with fewer complications are often associated with accelerated gastric emptying, which exacerbates postprandial glycaemic excursions. Moreover, gastric emptying appears to be more rapid in Han Chinese patients with T2D, as compared to Caucasian patients with T2D.
The proposed study will (i) compare the rate of gastric emptying in newly diagnosed, Chinese patients with T2D to non-diabetic controls, (ii) evaluate the relationship between gastric emptying and glycaemic indices, including measures of glucose variability, and (iii) determine whether gastric emptying is altered by glucose-lowering therapies.
Study Overview
Detailed Description
A total of 100 newly diagnosed Han Chinese patients with type 2 diabetes will be recruited into the study through the Department of Endocrinology, Nanjing first Hospital. Following enrolment, patients will receive either an intensive insulin pump therapy for a months, or a combination of oral glucose-lowering agents (including metformin, DPP-4 inhibitors and/or sodium-glucose co-transporter-2 inhibitors), or a combination of oral glucose-lowering agents and injectable glucagon-like peptide-1 (GLP-1) receptor agonists for 3 months. Before the commencement of the therapy and on days 30 and 90, patients will attend the hospital for continuous glucose monitoring over 24 hours and measurement of gastric emptying using a 75 g oral glucose tolerance test (OGTT).
During their hospital stay, patients will consume 3 standard meals (i.e. breakfast, lunch and dinner) provided by the Department of Clinical Nutrition, with their glucose levels tracked by continuous glucose monitoring system (CGMS). Following the dinner, subjects will be asked to fast from solids and liquids (other than water) until the following morning, when they will be subjected to an OGTT at ~0900h. An intravenous cannula will be placed into a vein on the forearm. Subjects will be asked to consume a glucose drink containing 75 g glucose and 150mg 13C-acetate, within 5 min for the assessment of gastric emptying, postprandial glycemic and hormonal responses. Breath samples will be collected immediately before, and every 15 minutes after the drink for 3 hours for the measurement of gastric emptying. Venous blood samples will be taken at t = 0, 30, 60, 90, 120, 150 and 180 min for the measurements of plasma glucose, serum insulin, C-peptide, glucagon, total GLP-1, GIP and bile acids concentrations. Blood pressure and heart rate will be measured before and every 15 min after the drink for 3 hours.
Study Type
Enrollment (Actual)
Contacts and Locations
Study Locations
-
-
Jiangsu
-
Nanjing, Jiangsu, China, 210000
- Nanjing First Hospital
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Sampling Method
Study Population
Description
Inclusion Criteria:
- Patients newly diagnosed of type 2 diabetes as defined by published Criteria of World Health Organization in 1999; with HbA1c ≥ 7%, age ≥ 18 years of age and ≤ 80 years old, and willing to receive anti-diabetic treatments,
- Non-diabetic controls, with BMI and age matched to patients with type 2 diabetes
Exclusion Criteria:
- Patients with a fasting blood glucose ≤ 3.9mmol/L;
- Patients with insulin allergy;
- Patients with severe gastrointestinal symptoms and diseases;
- Patients with gastrointestinal surgery history;
- Use of any medication that may influence gastrointestinal motor function, body weight or appetite (opiates, anticholinergics, levodopa, clonidine, nitrates, tricyclic antidepressants, selective serotonin re-uptake inhibitors, phosphodiesterase type 5 inhibitors, sumatriptan, metoclopramide, domperidone, cisapride, prucalopride, or erythromycin);
- Patients with major cardiovascular disease event (e.g., stroke, symptomatic peripheral artery disease, myocardial infarction, percutaneous coronary or peripheral artery angioplasty or coronary artery bypass surgery) in the previous 6 months;
- Patients with liver dysfunction (aspartate aminotransferase or alanine aminotransferase level of more than two times the upper limit of normal range) or renal dysfunction (creatinine > 150 μmol/L or GFR < 60 mL/min/1.73m2);
- Patients with severe anemia and hemoglobin disorders (Hb < 60 g/L);
- Patients with infected injection site or coagulation disorders;
- Patients who are pregnant.
Study Plan
How is the study designed?
Design Details
- Observational Models: Cohort
- Time Perspectives: Prospective
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
patients with newly diagnosed type 2 diabetes
Newly diagnosed, drug-naïve, Chinese patients with type 2 diabetes.
|
The anti-diabetic treatments include insulin glargine, insulin aspart, GLP-1 receptor agonist, DPP-4 inhibitor, SGLT-2 inhibitor, metformin, sulfonylureas and/or gliclazide.
Therapeutic dose of each drug follows recommendation by the treating doctor.
|
Non-diabetic control subjects
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Gastric-half emptying time of the 75 g glucose drink
Time Frame: Baseline, 1 month and 3 months in diabetic group
|
The Change in gastric-half emptying time (min) before and after the treatment
|
Baseline, 1 month and 3 months in diabetic group
|
Gastric-half emptying time of the 75 g glucose drink
Time Frame: Baseline in both diabetic and non-diabetic group
|
The difference in gastric-half emptying time (min) between subjects with and without type 2 diabetes
|
Baseline in both diabetic and non-diabetic group
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
The mean blood glucose level
Time Frame: Baseline, 1 month and 3 months in the diabetic group
|
The mean blood glucose level (mmol/L) during the 24 hours continuous glucose monitoring.
|
Baseline, 1 month and 3 months in the diabetic group
|
The mean amplitude of glycemic excursion
Time Frame: Baseline, 1 month and 3 months in the diabetic group
|
The mean amplitude of glycemic excursion (mmol/L) during the 24 hours continuous glucose monitoring.
|
Baseline, 1 month and 3 months in the diabetic group
|
The percentage of blood glucose levels within the target range
Time Frame: Baseline, 1 month and 3 months in the diabetic group
|
The percentage of blood glucose levels within the target range (%) during the 24 hours continuous glucose monitoring.
|
Baseline, 1 month and 3 months in the diabetic group
|
Serum insulin concentrations
Time Frame: t = 0, 30, 60, 120 and 180 min (t = 0 is when 75 g glucose drink is given) on baseline, 1 month and 3 months in the diabetic group
|
The differences in the incremental under the curve from 0 to 180 min (iAUC0-180min) for serum insulin (mU/L) in response to a 75 g glucose drink before and after the treatment. The incremental area under the curve (iAUC) is calculated using the trapezoidal rule. |
t = 0, 30, 60, 120 and 180 min (t = 0 is when 75 g glucose drink is given) on baseline, 1 month and 3 months in the diabetic group
|
Serum C-peptide concentrations
Time Frame: t = 0, 30, 60, 120 and 180 min (t = 0 is when 75 g glucose drink is given) on baseline, 1 month and 3 months in the diabetic group
|
The differences in the incremental area under the curve from 0 to 180 min (iAUC0-180min) for serum C-peptide (ng/mL) in response to a 75 g glucose drink before and after the treatment.
|
t = 0, 30, 60, 120 and 180 min (t = 0 is when 75 g glucose drink is given) on baseline, 1 month and 3 months in the diabetic group
|
Serum total GLP-1 concentrations
Time Frame: t = 0, 30, 60, 120 and 180 min (t = 0 is when 75 g glucose drink is given) on baseline, 1 month and 3 months in the diabetic group
|
The differences in the incremental under the curve from 0 to 180 min (iAUC0-180min) for serum total GLP-1 (pmol/L) in response to a 75 g glucose drink before and after the treatment.
|
t = 0, 30, 60, 120 and 180 min (t = 0 is when 75 g glucose drink is given) on baseline, 1 month and 3 months in the diabetic group
|
Serum total GIP concentrations
Time Frame: t = 0, 30, 60, 120 and 180 min (t = 0 is when 75 g glucose drink is given) on baseline, 1 month and 3 months in the diabetic group
|
The differences in the incremental under the curve from 0 to 180 min (iAUC0-180min) for serum total GIP (pmol/L) in response to a 75 g glucose drink before and after the treatment.
|
t = 0, 30, 60, 120 and 180 min (t = 0 is when 75 g glucose drink is given) on baseline, 1 month and 3 months in the diabetic group
|
Serum bile acid concentrations
Time Frame: Baseline, 1 month and 3 months in the diabetic group
|
The differences in the fasting serum bile acid concentrations (μmol/L) before and after the treatment.
|
Baseline, 1 month and 3 months in the diabetic group
|
Systolic blood pressure
Time Frame: t = 0, 15, 30, 45, 60,75, 90, 105, 120, 135, 150, 165 and 180 min (t = 0 is when 75 g glucose drink is given) on baseline, 1 month and 3 months in the diabetic group
|
The differences in systolic blood pressure (mmHg) in response to the 75 g glucose drink before and after the treatment.
|
t = 0, 15, 30, 45, 60,75, 90, 105, 120, 135, 150, 165 and 180 min (t = 0 is when 75 g glucose drink is given) on baseline, 1 month and 3 months in the diabetic group
|
Diastolic blood pressure
Time Frame: t = 0, 15, 30, 45, 60,75, 90, 105, 120, 135, 150, 165 and 180 min (t = 0 is when 75 g glucose drink is given) on baseline, 1 month and 3 months in the diabetic group
|
The differences in diastolic blood pressure (mmHg) in response to the 75 g glucose drink before and after the treatment.
|
t = 0, 15, 30, 45, 60,75, 90, 105, 120, 135, 150, 165 and 180 min (t = 0 is when 75 g glucose drink is given) on baseline, 1 month and 3 months in the diabetic group
|
Heart rate
Time Frame: t = 0, 15, 30, 45, 60,75, 90, 105, 120, 135, 150, 165 and 180 min (t = 0 is when 75 g glucose drink is given) on baseline, 1 month and 3 months in the diabetic group
|
The differences in heart rate (beats/min) in response to the 75 g glucose drink before and after the treatment.
|
t = 0, 15, 30, 45, 60,75, 90, 105, 120, 135, 150, 165 and 180 min (t = 0 is when 75 g glucose drink is given) on baseline, 1 month and 3 months in the diabetic group
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Tongzhi Wu, PhD, The University of Adelaide
- Principal Investigator: Jianhua Ma, PhD, The First Affiliated Hospital with Nanjing Medical University
Publications and helpful links
General Publications
- Xie C, Huang W, Wang X, Trahair LG, Pham HT, Marathe CS, Young RL, Jones KL, Horowitz M, Rayner CK, Wu T. Gastric emptying in health and type 2 diabetes: An evaluation using a 75 g oral glucose drink. Diabetes Res Clin Pract. 2021 Jan;171:108610. doi: 10.1016/j.diabres.2020.108610. Epub 2020 Dec 7.
- Wang X, Xie C, Marathe CS, Malbert CH, Horowitz M, Jones KL, Rayner CK, Sun Z, Wu T. Disparities in gastric emptying and postprandial glycaemia between Han Chinese and Caucasians with type 2 diabetes. Diabetes Res Clin Pract. 2020 Jan;159:107951. doi: 10.1016/j.diabres.2019.107951. Epub 2019 Nov 29.
- Goyal RK. Gastric Emptying Abnormalities in Diabetes Mellitus. N Engl J Med. 2021 May 6;384(18):1742-1751. doi: 10.1056/NEJMra2020927. No abstract available.
- Watson LE, Xie C, Wang X, Li Z, Phillips LK, Sun Z, Jones KL, Horowitz M, Rayner CK, Wu T. Gastric Emptying in Patients With Well-Controlled Type 2 Diabetes Compared With Young and Older Control Subjects Without Diabetes. J Clin Endocrinol Metab. 2019 Aug 1;104(8):3311-3319. doi: 10.1210/jc.2018-02736.
- Phillips LK, Deane AM, Jones KL, Rayner CK, Horowitz M. Gastric emptying and glycaemia in health and diabetes mellitus. Nat Rev Endocrinol. 2015 Feb;11(2):112-28. doi: 10.1038/nrendo.2014.202. Epub 2014 Nov 25.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- KY20220214-08
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Type 2 Diabetes
-
University of Erlangen-Nürnberg Medical SchoolCompletedType 2-diabetesGermany
-
Antonio Di MauroCompletedType-2 DiabetesItaly
-
DiaMedica Therapeutics IncCompletedDiabetes Type 2Netherlands
-
RenJi HospitalUnknownType 2 Diabetes.China
-
CSPC Baike (Shandong) Biopharmaceutical Co., Ltd.Not yet recruiting
-
Beijing Chao Yang HospitalNot yet recruitingType 2 Diabetes MellitusChina
-
Vinmec Research Institute of Stem Cell and Gene...CompletedType 2 Diabetes MellitusVietnam
-
Tehran University of Medical SciencesCompleted
-
Insulet CorporationCompletedType 2 Diabetes MellitusUnited States
-
Seoul National University Bundang HospitalAstellas Pharma Korea, Inc.CompletedType 2 Diabetes MellitusKorea, Republic of
Clinical Trials on Anti-Diabetics
-
Centre Hospitalier Universitaire de la RéunionAcademic Health Science CentresUnknownCardiovascular Disease | Diabetes | AtherothrombosisFrance
-
Johns Hopkins Bloomberg School of Public HealthMedifast, Inc.CompletedObesity | Type 2 Diabetes Mellitus
-
University of MinnesotaUniversity of WashingtonCompleted
-
Centro de Estudios en Alimentación y Nutrición,...Completed
-
University of Missouri-ColumbiaCompletedObesity | Type 2 Diabetes MellitusUnited States
-
University of New MexicoTerminated
-
Seoul National University HospitalCompletedDiabetes MellitusKorea, Republic of
-
Duke UniversityVerizon WirelessCompletedPeripheral Artery DiseaseUnited States
-
Ain Shams UniversityUnknownDiabetes Mellitus, Type 2Egypt
-
SanofiTerminatedDiabetes Mellitus, Type 2Australia