Efficacy Comparison of Polyethylene Glycol Loxenatide and Gliclazide on the Brain Function in T2DM Patients: a Randomized, Parallel Controlled Clinical Trial
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Sponsor
- Enrollment
- 58
- Locations
- 1
- Primary Endpoint
- Change of olfactory brain activation by fMRI
Study Overview
Brief Summary
This is a prospective, randomized, open label, parallel,4-month study to explore and evaluate the therapeutic effects of polyethylene glycol loxenatide on the cognitive function, olfactory function, and odor-induced brain activation in T2DM patients with normal cognitive status or MCI.
Detailed Description
This is a prospective, randomized, open label, parallel, 4-month study to explore and evaluate the therapeutic effects of polyethylene glycol loxenatide on the cognitive function, olfactory function, and odor-induced brain activation in T2DM patients with normal cognitive status or MCI inadequately controlled with metformin monotherapy. The control group was treated with Gliclazide. There are 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 58 patients (29 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 loxenatide 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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 40 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •patients with type 2 diabetes mellitus ;
- •Aged:40 -75 years ;
- •Cognitive function assessment suggests normal status or mild cognitive impairment;
- •a stable dose of metformin monotherapy (≥1,500 mg daily) for at least 90 days,
- •HbA1c 7 - 10%;
- •≥6 years of education;
- •Right-handed.
Exclusion Criteria
- •patients unable to complete brain MRI scanning;
- •nasal disease that affected olfactory function;
- •hepatic dysfunction with liver transaminases > 2.5 times upper normal limits and renal impairment with an estimated glomerular filtration rate < 60ml/min/1.73m2 ;
- •acute cardio/cerebrovascular disease, psychiatric disorders, pancreatitis, acute infection, malignant tumor,thyroid disease and homorne drug use;
- •a history of related drug allergy;
- •alcohol or drug misuse;
- •pregnant, breast-feeding or intending to become pregnant.
Arms & Interventions
loxenatide Group
loxenatide will be initiated and maintained at 0.2mg once weekly 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 loxenatide 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: loxenatide Group (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 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: Gliclazide Group (Drug)
Outcomes
Primary Outcomes
Change of olfactory brain activation by fMRI
Time Frame: from baseline to 4-month 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 4-month follow-up)
- Change of metabolism(from baseline to 4-month follow-up)
Investigators
Yan Bi
Chief Physician
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School