A Prospective, Randomized, Open Label, Parallel, 16-week Study to Explore and Evaluate the Therapeutic Effects of Liraglutid, Dapagliflozin and Acarbose on the Cognitive Function, Olfactory Function, and Odor-induced Brain Activation in Overweight/Obese Patients With T2DM Inadequately Controlled With Metformin Monotherapy.
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 87
- 试验地点
- 1
- 主要终点
- Change of olfactory brain activation by fMRI
研究概览
简要总结
This is a prospective, randomized, open label, parallel, 16-week study to explore and evaluate the therapeutic effects of liraglutid, dapagliflozin and acarbose on the cognitive function, olfactory function, and odor-induced brain activation in overweight/obese patients with type 2 diabetes mellitus(T2DM) inadequately controlled with metformin monotherapy.
详细描述
This is a prospective, randomized, open label, parallel, 16-week study to explore and evaluate the therapeutic effects of liraglutid, dapagliflozin and acarbose on the cognitive function, olfactory function, and odor-induced brain activation in overweight/obese patients with T2DM inadequately controlled with metformin monotherapy.We have 1 principle investigator, 6 sub-investigators and 1 nurse in research centre. The sub-investigators will screen in the outpatient and inpatient departments to enroll 87 patients (29 for each arm) totally with the inclusion and exclusion criteria in 12 months. The patients will be randomized at a 1:1:1 ratio into liraglutid, dapagliflozin and acarbose 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 40 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≧ 40 and ≦75 years old
- •T2DM patients controlled with metformin monotherapy with stable, maximum tolerated doses (≧1500mg/d, ≧12 weeks)
- •HbA1c>7% and ≤9%
- •Body mass index(BMI) ≥25kg/m2 and with stable weight during previous 3 months
- •Right handedness
- •Possessed over 6-year education
- •Provision of informed consent prior to any study specific procedures
- •Mini-Mental State Examination (MMSE) >24
排除标准
- •Allergies to research drugs
- •Treated with glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, sodium-glucose cotransporter 2 inhibitors, insulins, and glycosidase inhibitors in the previous 6 months
- •Moderate to severe renal dysfunction defined as estimated glomerular filtration rate(eGFR)<60ml/min/1.73m2 ( eGFR was estimated by CKD-EPI creatinine equation using an online calculator).
- •Hepatic insufficiency
- •A history of neurological and psychiatric disorders, nasal pathologies, abnormal thyroid, pancreatitis, repeated urinary tract infection, chronic gastrointestinal dysfunction, any disease that may worsen by intestinal flatulence, alcohol or substance abuse, steroid treatment
- •Any acute disease
- •Inability to undergo tests or MRI scanning
- •Pregnant or lactating women
- •Participating in other clinical trials at the same time or within 6 months prior to the start of the trial
研究组 & 干预措施
Liraglutid
Liraglutid will be titrated from 0.6mg/day to a final dose 1.8mg/day during the first 2 weeks, if well tolerated. 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 liraglutid 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.
干预措施: Liraglutid (Drug)
Dapagliflozin
Dapagliflozin will be initiated and maintained at 10mg/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 dapagliflozin 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.
干预措施: Dapagliflozin (Drug)
Acarbose
Acarbose will be initiated at 50mg three times daily for the first week, and then titrated to100mg three times daily if appropriate. 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 acarbose 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.
干预措施: Acarbose (Drug)
结局指标
主要结局
Change of olfactory brain activation by fMRI
时间窗: from baseline to 16 weeks' follow-up.
Compare the change of olfactory brain activation by fMRI from baseline to 16 weeks' follow-up
次要结局
- Change of cognitive function(from baseline to 16 weeks' follow-up.)
- Proportion of patients whose MoCA<26 scores(at baseline and at 16 weeks' follow-up.)
- Change of blood glycaemic control(from baseline to 16 weeks' follow-up)
- Proportion of patients whose HbA1c<7%(at 16 weeks' follow-up.)
- Proportion of patients whose weight loss>3% and >5%(from baseline to 16 weeks' follow-up.)
- Olfactory threshold test(from baseline to 16 weeks' follow-up.)
研究者
Dalong Zhu
Chief Physician
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School