Back to resultsEffects of Henagliflozin on the Brain Function in T2DM Patients With Mild Cognitive Impairment: a Randomized, Parallel Controlled Clinical Trial
Primary Purpose
Type 2 Diabetes Mellitus, Mild Cognitive Impairment
Status
Recruiting
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
Henagliflozin
Gliclazide
Sponsored by
About this trial
This is an interventional treatment trial for Type 2 Diabetes Mellitus focused on measuring Functional MRI, Cognition, Olfactory function, Henagliflozin and Gliclazide
Eligibility Criteria
Inclusion Criteria: patients with type 2 diabetes mellitus ; Aged:55 -75 years ; Cognitive function assessment suggests mild cognitive impairment; A stable glucose-lowering regimen include Metformin alone or in combination with antidiabetic drugs other than SGLT2 inhibitors or sulfonylureas/glinides, or basic insulin for more than 2 months, and the dose of metformin≥1.0g/d; HbA1c 7 - 10%; ≥6 years of education; Right-handed. Exclusion Criteria: Cognitive function assessment suggests normal cognition or dementia; Other dementia related neurological diseases or depression, Mental dysplasia, mania, schizophrenia, etc in the past 2 years; Central nervous system diseases, including brain trauma, intracranial hemorrhage, acute cerebral infarction, etc; Severe sinusitis, nasal cavity and sinus polyps, skull base or nasopharyngeal tumors and other space occupying lesions; Congenital diseases and traumatic history of nose, maxillofacial and skull base affecting olfaction. With symptoms of upper respiratory tract infection, including nasal congestion, runny nose, fever, etc. on the day of MR examination; Diabetic Acute and chronic complications, including diabetic ketoacidosis, diabetic ketoacidosis; a hyperglycemic hyperosmolar state or severe hypoglycemic coma, etc. Severe impairment of heart, liver, kidney and other organs; Contraindications of MRI examination, such as implantation of metal prosthesis in vivo, claustrophobia, etc; Pregnant and lactating women; Receive other test drugs currently or within 3 months before participating in the project; Known or suspected allergic history to the test drug or similar drugs; SGLT2 inhibitor and sulfonylureas/glinides were used in recent 3 months.
Sites / Locations
- Division of Endocrinology, the Affiliated Drum Tower Hospital of Nanjing UniversityRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Henagliflozin Group
Gliclazide Group
Arm Description
Henagliflozin will be initiated and maintained at 5mg/ day every morning until the completion of the study. Meanwhile, all patients will also continue on their existing dose and regimen of metformin throughout the study. Visits at 4-week intervals will be performed to evaluate the safety of drugs. Metformin dose can be reduced in response to hypoglycaemia, but Empagliflozin could not be adjusted. If the plasma glucose still not achieve the target at the maximum dose, the maximum dose will be maintained until the completion of the study.
Gliclazide will be initiated and maintained at 30mg/ day every morning until the completion of the study. Meanwhile, all patients will also continue on their existing dose and regimen of metformin throughout the study. Visits at 4-week intervals will be performed to evaluate the safety of drugs. Metformin dose can be reduced in response to hypoglycaemia, but Gliclazide could not be adjusted. If the plasma glucose still not achieve the target at the maximum dose, the maximum dose will be maintained until the completion of the study.
Outcomes
Primary Outcome Measures
Change of olfactory brain activation by fMRI
Whether the activation degree of olfactory task fMRI brain area in the two groups after intervention was different from that before treatment and the difference of changes between the two groups. All patients underwent odor-induced task fMRI on a 3.0T MR scanner with 222 volumes for task fMRI and 230 volumes for resting-state fMRI. The odor-induced task consisted of "fresh air" "rest" and "scent". Odor-induced brain activation was assessed by a general linear model using Statistical Parametric Mapping 12 (SPM12) software. Following extraction of the three separate conditions "fresh air," "scent," and "rest" from the whole sequence, contrasts were made for each participant between "fresh air > rest" and "scent > rest." Odor-induced fMRI data were analyzed in the mask of the olfactory network, including the regions of bilateral parahippocampus, amygdala, piriform cortex, insula, orbitofrontal cortex, hippocampus, and entorhinal cortices.
Secondary Outcome Measures
Change of cognitive function
Type 2 diabetes mellitus patients with MCI were relieved of mild cognitive impairment , which means MoCA scores were not less than 26 points after treatment, or improved referring to the MoCA score or the RBANS total score increased by 0.5 standard deviation compared with baseline after treatment.
Olfactory threshold test
Whether the olfactory threshold scores of the two groups after intervention were higher than those before treatment and the difference of changes between the two groups. Olfactory testing was performed using Olfactory Function Assessment by Computerized Testing (OLFACT) (Osmic Enterprises, Inc.). Based on the University of Pennsylvania Smell Identification Test (UPSIT), OLFACT tests were computerized, standardized, and self-administered. Higher scores indicated better ability to detect odors. Threshold testing was performed by a series of binary dilutions of n-butanol solution in light mineral oil, and scores ranged from 1 to 13.5.
Change of metabolism
The changes of glycosylated hemoglobin among the two groups before and after intervention. The level of glycosylated hemoglobin <7% means better glucose metabolism.
Full Information
NCT ID
NCT06085703
First Posted
October 10, 2023
Last Updated
October 10, 2023
Sponsor
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
1. Study Identification
Unique Protocol Identification Number
NCT06085703
Brief Title
Effects of Henagliflozin on the Brain Function in T2DM Patients With Mild Cognitive Impairment: a Randomized, Parallel Controlled Clinical Trial
Official Title
A Prospective, Randomized, Open Label, Parallel, 6-month Study to Explore and Evaluate the Therapeutic Effects of Henagliflozin on the Cognitive Function, Olfactory Function, and Odor-induced Brain Activation in T2DM Patients With Mild Cognitive Impairment.
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 1, 2023 (Actual)
Primary Completion Date
June 30, 2025 (Anticipated)
Study Completion Date
June 30, 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is a prospective, randomized, open label, parallel,6-month study to explore and evaluate the therapeutic effects of Henagliflozin on the cognitive function, olfactory function, and odor-induced brain activation in T2DM patients with mild cognitive impairment (MCI).
Detailed Description
This is a prospective, randomized, open label, parallel, 6-month study to explore and evaluate the therapeutic effects of Henagliflozin on the cognitive function, olfactory function, and odor-induced brain activation in T2DM patients with MCI inadequately controlled with metformin monotherapy. The control group was treated with Gliclazide. We have 1 principal investigator, 6 sub-investigators and 1 nurse in research centre. The sub-investigators will screen in the outpatient and inpatient departments to enroll 60 patients (30 patients for each arm) totally with the inclusion and exclusion criteria in 9 months. The patients will be randomized at a 1:1 ratio into Henagliflozin and Gliclazide treatment group with a computer-generated random order. All patients will also continue on their existing dose and regimen of metformin throughout the study. At the baseline, clinical information collection, 100g-steamed bread meal test, biochemical measurement, body composition analysis, cognitive assessment, olfactory test and functional magnetic resonance imaging(fMRI) scan will be conducted for all patients. During the treatment period, visits at 4-week intervals will be performed to evaluate the safety of drugs and adjust the dose of metformin if hypoglycaemia occurs; meanwhile, fasting and 2-hour postprandial plasma glucose assayed by fingerstick, physical examination, and olfactory test will be conducted. At the end of the study, all of the assessments will be performed again for all recruited subjects, including early withdrawal patients.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 2 Diabetes Mellitus, Mild Cognitive Impairment
Keywords
Functional MRI, Cognition, Olfactory function, Henagliflozin and Gliclazide
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
60 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Henagliflozin Group
Arm Type
Experimental
Arm Description
Henagliflozin will be initiated and maintained at 5mg/ day every morning until the completion of the study. Meanwhile, all patients will also continue on their existing dose and regimen of metformin throughout the study. Visits at 4-week intervals will be performed to evaluate the safety of drugs. Metformin dose can be reduced in response to hypoglycaemia, but Empagliflozin could not be adjusted. If the plasma glucose still not achieve the target at the maximum dose, the maximum dose will be maintained until the completion of the study.
Arm Title
Gliclazide Group
Arm Type
Experimental
Arm Description
Gliclazide will be initiated and maintained at 30mg/ day every morning until the completion of the study. Meanwhile, all patients will also continue on their existing dose and regimen of metformin throughout the study. Visits at 4-week intervals will be performed to evaluate the safety of drugs. Metformin dose can be reduced in response to hypoglycaemia, but Gliclazide could not be adjusted. If the plasma glucose still not achieve the target at the maximum dose, the maximum dose will be maintained until the completion of the study.
Intervention Type
Drug
Intervention Name(s)
Henagliflozin
Other Intervention Name(s)
metformin
Intervention Description
Henagliflozin will be initiated and maintained at 5mg/day every morning. If necessary, the dose can be increased to 10mg once daily. All patients will also continue on their existing dose and regimen of metformin throughout the study.
Intervention Type
Drug
Intervention Name(s)
Gliclazide
Other Intervention Name(s)
metformin
Intervention Description
Gliclazide will be initiated and maintained at 30mg/day every morning. If necessary, the dose can be increased to 120mg once daily. All patients will also continue on their existing dose and regimen of metformin throughout the study.
Primary Outcome Measure Information:
Title
Change of olfactory brain activation by fMRI
Description
Whether the activation degree of olfactory task fMRI brain area in the two groups after intervention was different from that before treatment and the difference of changes between the two groups. All patients underwent odor-induced task fMRI on a 3.0T MR scanner with 222 volumes for task fMRI and 230 volumes for resting-state fMRI. The odor-induced task consisted of "fresh air" "rest" and "scent". Odor-induced brain activation was assessed by a general linear model using Statistical Parametric Mapping 12 (SPM12) software. Following extraction of the three separate conditions "fresh air," "scent," and "rest" from the whole sequence, contrasts were made for each participant between "fresh air > rest" and "scent > rest." Odor-induced fMRI data were analyzed in the mask of the olfactory network, including the regions of bilateral parahippocampus, amygdala, piriform cortex, insula, orbitofrontal cortex, hippocampus, and entorhinal cortices.
Time Frame
from baseline to 6-month follow-up
Secondary Outcome Measure Information:
Title
Change of cognitive function
Description
Type 2 diabetes mellitus patients with MCI were relieved of mild cognitive impairment , which means MoCA scores were not less than 26 points after treatment, or improved referring to the MoCA score or the RBANS total score increased by 0.5 standard deviation compared with baseline after treatment.
Time Frame
from baseline to 6-month follow-up
Title
Olfactory threshold test
Description
Whether the olfactory threshold scores of the two groups after intervention were higher than those before treatment and the difference of changes between the two groups. Olfactory testing was performed using Olfactory Function Assessment by Computerized Testing (OLFACT) (Osmic Enterprises, Inc.). Based on the University of Pennsylvania Smell Identification Test (UPSIT), OLFACT tests were computerized, standardized, and self-administered. Higher scores indicated better ability to detect odors. Threshold testing was performed by a series of binary dilutions of n-butanol solution in light mineral oil, and scores ranged from 1 to 13.5.
Time Frame
from baseline to 6-month follow-up
Title
Change of metabolism
Description
The changes of glycosylated hemoglobin among the two groups before and after intervention. The level of glycosylated hemoglobin <7% means better glucose metabolism.
Time Frame
from baseline to 6-month follow-up
10. Eligibility
Sex
All
Minimum Age & Unit of Time
55 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
patients with type 2 diabetes mellitus ;
Aged:55 -75 years ;
Cognitive function assessment suggests mild cognitive impairment;
A stable glucose-lowering regimen include Metformin alone or in combination with antidiabetic drugs other than SGLT2 inhibitors or sulfonylureas/glinides, or basic insulin for more than 2 months, and the dose of metformin≥1.0g/d;
HbA1c 7 - 10%;
≥6 years of education;
Right-handed.
Exclusion Criteria:
Cognitive function assessment suggests normal cognition or dementia;
Other dementia related neurological diseases or depression, Mental dysplasia, mania, schizophrenia, etc in the past 2 years; Central nervous system diseases, including brain trauma, intracranial hemorrhage, acute cerebral infarction, etc;
Severe sinusitis, nasal cavity and sinus polyps, skull base or nasopharyngeal tumors and other space occupying lesions;
Congenital diseases and traumatic history of nose, maxillofacial and skull base affecting olfaction.
With symptoms of upper respiratory tract infection, including nasal congestion, runny nose, fever, etc. on the day of MR examination;
Diabetic Acute and chronic complications, including diabetic ketoacidosis, diabetic ketoacidosis; a hyperglycemic hyperosmolar state or severe hypoglycemic coma, etc.
Severe impairment of heart, liver, kidney and other organs;
Contraindications of MRI examination, such as implantation of metal prosthesis in vivo, claustrophobia, etc;
Pregnant and lactating women;
Receive other test drugs currently or within 3 months before participating in the project;
Known or suspected allergic history to the test drug or similar drugs; SGLT2 inhibitor and sulfonylureas/glinides were used in recent 3 months.
Facility Information:
Facility Name
Division of Endocrinology, the Affiliated Drum Tower Hospital of Nanjing University
City
Nanjing
State/Province
Jiangsu
ZIP/Postal Code
210008
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yan Bi, MD, PhD
Phone
86-25-83-105302
Email
biyan@nju.edu.cn
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Citations:
PubMed Identifier
31221697
Citation
Zhang Z, Zhang B, Wang X, Zhang X, Yang QX, Qing Z, Zhang W, Zhu D, Bi Y. Olfactory Dysfunction Mediates Adiposity in Cognitive Impairment of Type 2 Diabetes: Insights From Clinical and Functional Neuroimaging Studies. Diabetes Care. 2019 Jul;42(7):1274-1283. doi: 10.2337/dc18-2584. Epub 2019 May 21.
Results Reference
background
PubMed Identifier
29500313
Citation
Zhang Z, Zhang B, Wang X, Zhang X, Yang QX, Qing Z, Lu J, Bi Y, Zhu D. Altered Odor-Induced Brain Activity as an Early Manifestation of Cognitive Decline in Patients With Type 2 Diabetes. Diabetes. 2018 May;67(5):994-1006. doi: 10.2337/db17-1274. Epub 2018 Mar 2.
Results Reference
background
PubMed Identifier
35263425
Citation
Cheng H, Zhang Z, Zhang B, Zhang W, Wang J, Ni W, Miao Y, Liu J, Bi Y. Enhancement of Impaired Olfactory Neural Activation and Cognitive Capacity by Liraglutide, but Not Dapagliflozin or Acarbose, in Patients With Type 2 Diabetes: A 16-Week Randomized Parallel Comparative Study. Diabetes Care. 2022 May 1;45(5):1201-1210. doi: 10.2337/dc21-2064.
Results Reference
background
Learn more about this trial
Effects of Henagliflozin on the Brain Function in T2DM Patients With Mild Cognitive Impairment: a Randomized, Parallel Controlled Clinical Trial
We'll reach out to this number within 24 hrs