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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.

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ClinicalTrials.gov Identifier: NCT03961659
Recruitment Status : Recruiting
First Posted : May 23, 2019
Last Update Posted : May 23, 2019
Sponsor:
Information provided by (Responsible Party):
Dalong Zhu, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Type 2 Diabetes Mellitus Obesity Cognitive Impairment Drug: Liraglutid Drug: Dapagliflozin Drug: Acarbose Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Estimated 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.
Estimated Study Start Date : May 2019
Estimated Primary Completion Date : August 2020
Estimated Study Completion Date : February 2021


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 Name: 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 Name: 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 Name: metformin




Primary Outcome Measures :
  1. Change of olfactory brain activation by fMRI [ Time Frame: 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 :
  1. Change of cognitive function [ Time Frame: 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.

  2. Proportion of patients whose MoCA<26 scores [ Time Frame: 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.

  3. Change of blood glycaemic control [ Time Frame: from baseline to 16 weeks' follow-up ]
    Compare the change of glycosylated hemoglobin(HbA1c) from baseline to 16 weeks' follow-up

  4. Proportion of patients whose HbA1c<7% [ Time Frame: at 16 weeks' follow-up. ]
    Analyze the proportion of patients whose HbA1c<7% at 16 weeks' follow-up.

  5. Proportion of patients whose weight loss>3% and >5% [ Time Frame: from baseline to 16 weeks' follow-up. ]
    Analyze the proportion of patients whose weight loss>3% and >5%

  6. Olfactory threshold test [ Time Frame: 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.



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Ages Eligible for Study:   40 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03961659


Contacts
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Contact: Da long Zhu, MD, PhD 86-25-83-105302 zhudldr@gmail.com
Contact: Yan Bi, MD, PhD 86-25-83-105302 biyan@nju.edu.cn

Locations
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China, Jiangsu
at Division of Endocrinology, the Affiliated Drum Tower Hospital of Nanjing University Recruiting
Nanjing, Jiangsu, China, 210008
Contact: Dalong Zhu, MD,PhD    86-25-83-105302    zhudldr@gmail.com   
Contact: Yan Bi, MD,PhD    86-25-83-105302    biyan@nju.edu.cn   
Principal Investigator: Dalong Zhu, MD,PhD         
Sub-Investigator: Yan Bi, MD,PhD         
Sponsors and Collaborators
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

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Responsible Party: Dalong Zhu, Chief Physician, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
ClinicalTrials.gov Identifier: NCT03961659     History of Changes
Other Study ID Numbers: ZZ2019
First Posted: May 23, 2019    Key Record Dates
Last Update Posted: May 23, 2019
Last Verified: May 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Dalong Zhu, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School:
Functional MRI
Olfactory function
Liraglutid
Dapagliflozin
Acarbose
Additional relevant MeSH terms:
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Overweight
Cognitive Dysfunction
Body Weight
Signs and Symptoms
Cognition Disorders
Neurocognitive Disorders
Mental Disorders
Metformin
2-(3-(4-ethoxybenzyl)-4-chlorophenyl)-6-hydroxymethyltetrahydro-2H-pyran-3,4,5-triol
Acarbose
Hypoglycemic Agents
Physiological Effects of Drugs
Sodium-Glucose Transporter 2 Inhibitors
Molecular Mechanisms of Pharmacological Action
Glycoside Hydrolase Inhibitors
Enzyme Inhibitors