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.
Overview
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
- Enrollment
- 24
- Locations
- 1
- Primary Endpoint
- Change of olfactory brain activation by fMRI
Overview
Brief Summary
This is a prospective, randomized, open label, parallel, 16-week 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, 16-week 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 24 patients (12 patients for each arm) totally with the inclusion and exclusion criteria. 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 8-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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Single (Outcomes Assessor)
Eligibility Criteria
- Ages
- 55 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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;
Arms & Interventions
Henagliflozin Group
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 8-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.
Intervention: Henagliflozin (Drug)
Gliclazide Group
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 8-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: Gliclazide (Drug)
Outcomes
Primary Outcomes
Change of olfactory brain activation by fMRI
Time Frame: from baseline to 16-week follow-up
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 Outcomes
- Change of cognitive function(from baseline to 16-week follow-up)
- Olfactory threshold test(from baseline to 16-week follow-up)
- Change of metabolism(from baseline to 16-week follow-up)
Investigators
Zhu DaLong
Chief Physician
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School