Effects of Henagliflozin on the Brain Function in T2DM Patients With Mild Cognitive Impairment: a Randomized, Parallel Controlled Clinical Trial

NCT06085703 | Completed

• 1 other identifier: ZZ2023
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective, randomized, open label, parallel, 16-week study to explore and evaluate the therapeutic effects of Henagliflozin on the cognitive function, olfactory function, and odor-induced brain activation in T2DM patients with mild cognitive impairment (MCI).

Conditions

Type 2 Diabetes Mellitus; Mild Cognitive Impairment

Keywords

Functional MRI; Cognition; Olfactory function; Henagliflozin and Gliclazide

Outcome Measures

Primary Outcomes (1)

• Change of olfactory brain activation by fMRI

  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.

  from baseline to 16-week follow-up

Secondary Outcomes (3)

• Change of cognitive function

  from baseline to 16-week follow-up

• Olfactory threshold test

  from baseline to 16-week follow-up

• Change of metabolism

  from baseline to 16-week follow-up

Study Arms (2)

Henagliflozin Group

EXPERIMENTAL

Henagliflozin will be initiated and maintained at 5mg/ 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 8-week intervals will be performed to evaluate the safety of drugs. Metformin dose can be reduced in response to hypoglycaemia, but Empagliflozin 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: Henagliflozin

Gliclazide Group

EXPERIMENTAL

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 8-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.

Drug: Gliclazide

Interventions

Henagliflozin DRUG

Henagliflozin will be initiated and maintained at 5mg/day every morning. If necessary, the dose can be increased to 10mg once daily. All patients will also continue on their existing dose and regimen of metformin throughout the study.

Also known as: metformin

Henagliflozin Group

Gliclazide DRUG

Gliclazide will be initiated and maintained at 30mg/day every morning. If necessary, the dose can be increased to 120mg once daily. All patients will also continue on their existing dose and regimen of metformin throughout the study.

Also known as: metformin

Gliclazide Group

Eligibility Criteria

• Age: 55 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• patients with type 2 diabetes mellitus ;
• Aged: 55 - 75 years ;
• Cognitive function assessment suggests mild cognitive impairment;
• A stable glucose-lowering regimen include Metformin alone or in combination with antidiabetic drugs other than SGLT2 inhibitors or sulfonylureas/glinides, or basic insulin for more than 2 months, and the dose of metformin≥1.0g/d;
• HbA1c: 7 - 10%;
• ≥6 years of education;
• Right-handed.

You may not qualify if:

• Cognitive function assessment suggests normal cognition or dementia;
• Other dementia related neurological diseases or depression, Mental dysplasia, mania, schizophrenia, etc in the past 2 years; Central nervous system diseases, including brain trauma, intracranial hemorrhage, acute cerebral infarction, etc;
• Severe sinusitis, nasal cavity and sinus polyps, skull base or nasopharyngeal tumors and other space occupying lesions;
• Congenital diseases and traumatic history of nose, maxillofacial and skull base affecting olfaction.
• With symptoms of upper respiratory tract infection, including nasal congestion, runny nose, fever, etc. on the day of MR examination;
• Diabetic Acute and chronic complications, including diabetic ketoacidosis, diabetic ketoacidosis; a hyperglycemic hyperosmolar state or severe hypoglycemic coma, etc.
• Severe impairment of heart, liver, kidney and other organs;
• Contraindications of MRI examination, such as implantation of metal prosthesis in vivo, claustrophobia, etc;
• Pregnant and lactating women;
• Receive other test drugs currently or within 3 months before participating in the project;
• Known or suspected allergic history to the test drug or similar drugs; SGLT2 inhibitor and sulfonylureas/glinides were used in recent 3 months.

Sponsors & Collaborators

• The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School: lead

Study Sites (1)

Division of Endocrinology, the Affiliated Drum Tower Hospital of Nanjing University

Nanjing, Jiangsu, 210008, China

Location

Related Publications (3)

• 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.

  PMID: 31221697 BACKGROUND

• Zhang Z, Zhang B, Wang X, Zhang X, Yang QX, Qing Z, Lu J, Bi Y, Zhu D. Altered Odor-Induced Brain Activity as an Early Manifestation of Cognitive Decline in Patients With Type 2 Diabetes. Diabetes. 2018 May;67(5):994-1006. doi: 10.2337/db17-1274. Epub 2018 Mar 2.

  PMID: 29500313 BACKGROUND

• 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.

  PMID: 35263425 BACKGROUND

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Cognitive Dysfunction

Interventions

henagliflozin; Metformin; Gliclazide

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Benzenesulfonamides; Sulfonamides; Amides; Sulfonylurea Compounds; Urea; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician

Study Record Dates

• First Submitted: October 10, 2023
• First Posted: October 17, 2023
• Study Start: April 1, 2024
• Primary Completion: June 30, 2025
• Study Completion: June 30, 2025
• Last Updated: July 10, 2025

Record last verified: 2023-10

Locations

CN (1)