Clinical trial NCT06217887: Efficacy Comparison of Polyethylene Glycol Loxenatide and Gliclazide on the Brain Function in T2DM Patients
Official title: Efficacy Comparison of Polyethylene Glycol Loxenatide and Gliclazide on the Brain Function in T2DM Patients: a Randomized, Parallel Controlled Clinical Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Type 2 Diabetes Mellitus
Cognitive Function Abnormal
Keywords: Functional MRI
Cognition
Olfactory function
loxenatide
Lead sponsor: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Sponsor class: OTHER
First posted: 2024-01-23
Enrollment: 58
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change of olfactory brain activation by fMRI
timeFrame: from baseline to 4-month follow-up
Secondary outcomes:
measure: Change of cognitive function
timeFrame: from baseline to 4-month follow-up
measure: Change of metabolism
timeFrame: from baseline to 4-month follow-up
Other outcomes:
Locations:
city: Nanjing
country: China
facility: Division of Endocrinology, the Affiliated Drum Tower Hospital of Nanjing University
state: Jiangsu
Study officials:
References:
citation: Zhang Z, Zhang B, Wang X, Zhang X, Yang QX, Qing Z, Zhang W, Zhu D, Bi Y. Olfactory Dysfunction Mediates Adiposity in Cognitive Impairment of Type 2 Diabetes: Insights From Clinical and Functional Neuroimaging Studies. Diabetes Care. 2019 Jul;42(7):1274-1283. doi: 10.2337/dc18-2584. Epub 2019 May 21.
citation: Cheng H, Zhang Z, Zhang B, Zhang W, Wang J, Ni W, Miao Y, Liu J, Bi Y. Enhancement of Impaired Olfactory Neural Activation and Cognitive Capacity by Liraglutide, but Not Dapagliflozin or Acarbose, in Patients With Type 2 Diabetes: A 16-Week Randomized Parallel Comparative Study. Diabetes Care. 2022 May 1;45(5):1201-1210. doi: 10.2337/dc21-2064.