Effects of Liraglutid, Dapagliflozin and Acarbose on the Cognitive Function, Olfactory Function, and Odor-induced Brain Activation in Overweight/Obese T2DM Patients Controlled Inadequately With Metformin Monotherapy.

Sponsor

The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School (Other)

Overall Status

Unknown status

CT.gov ID

NCT03961659

Collaborator

(none)

Enrollment

Location

Arms

21.1

Anticipated Duration (Months)

4.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes Mellitus Obesity Cognitive Impairment	Drug: Liraglutid Drug: Dapagliflozin Drug: Acarbose	N/A

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

87 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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.

Anticipated Study Start Date :

May 1, 2019

Anticipated Primary Completion Date :

Aug 1, 2020

Anticipated Study Completion Date :

Feb 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 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.	Drug: Liraglutid Liraglutid will be titrated from 0.6mg/day to 1.8mg/day during the first 2 weeks, if well tolerated. All patients will also continue on their existing dose and regimen of metformin throughout the study. Other Names: metformin
Active Comparator: 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.	Drug: Dapagliflozin Dapagliflozin will be initiated and maintained at 10mg/day every morning until the completion of the study. All patients will also continue on their existing dose and regimen of metformin throughout the study. Other Names: metformin
Active Comparator: 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.	Drug: Acarbose Acarbose will be initiated at 50mg three times daily for the first week, and then titrated to 100mg three times daily if appropriate.All patients will also continue on their existing dose and regimen of metformin throughout the study. Other Names: metformin

Arm

Intervention/Treatment

Active Comparator: 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.

Drug: Liraglutid

Liraglutid will be titrated from 0.6mg/day to 1.8mg/day during the first 2 weeks, if well tolerated. All patients will also continue on their existing dose and regimen of metformin throughout the study.

Other Names:

metformin

Active Comparator: 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.

Drug: Dapagliflozin

Dapagliflozin will be initiated and maintained at 10mg/day every morning until the completion of the study. All patients will also continue on their existing dose and regimen of metformin throughout the study.

Other Names:

metformin

Active Comparator: 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.

Drug: Acarbose

Acarbose will be initiated at 50mg three times daily for the first week, and then titrated to 100mg three times daily if appropriate.All patients will also continue on their existing dose and regimen of metformin throughout the study.

Other Names:

metformin

Outcome Measures

Primary Outcome Measures

Change of olfactory brain activation by fMRI [from baseline to 16 weeks' follow-up.]
Compare the change of olfactory brain activation by fMRI from baseline to 16 weeks' follow-up

Secondary Outcome Measures

Change of cognitive function [from baseline to 16 weeks' follow-up.]
Compare the change of Montreal Cognitive Assessment (MoCA, beijing version) from baseline to 16 weeks' follow-up. MoCA score(ranging from 0 to 30)<26 is considered cognitive impairment and when the score is lower, the cognitive impairment is more serious. MoCA score ≥26 is considered normal cognition.
Proportion of patients whose MoCA<26 scores [at baseline and at 16 weeks' follow-up.]
Compare the 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]
Compare the change of glycosylated hemoglobin(HbA1c) from baseline to 16 weeks' follow-up
Proportion of patients whose HbA1c<7% [at 16 weeks' follow-up.]
Analyze the 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.]
Analyze the proportion of patients whose weight loss>3% and >5%
Olfactory threshold test [from baseline to 16 weeks' follow-up.]
The olfactory threshold test (score range 1-13.5) is determined based on a series of binary dilutions of the N-butanol solution in light mineral oil. The higher the score is, the more sensitive the participant is in detecting an odor. Scores of 8-10 were considered normal olfactory sensitivity, whereas scores of 1-3 signified olfactory dysfunction or anosmia, and scores of ≥10 indicate better olfactory sensitivity.

Eligibility Criteria

Criteria

Ages Eligible for Study:

40 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Exclusion Criteria:

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