Type 2 Diabetes MellitusNCT06085703
Effects of Henagliflozin on the Brain Function in T2DM Patients With Mild Cognitive Impairment: a Randomized, Parallel Controlled Clinical Trial
A study testing Henagliflozin and Gliclazide in people with Type 2 Diabetes Mellitus and Mild Cognitive Impairment, run by The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School at 1 site in China.
Trial 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). Read more about this study
- Who is it for?
- Ages 55 to 75 years
- Conditions the study is for
- Type 2 Diabetes Mellitus, Mild Cognitive Impairment
- What is being tested?
- Henagliflozin and Gliclazide
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteChina
- Study dates
- 1 Apr 2024to 30 Jun 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 55 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
China1 site
Division of Endocrinology, the Affiliated Drum Tower Hospital of Nanjing University
Nanjing, Jiangsu, 210008
About this study
Official title: A Prospective, Randomized, Open Label, Parallel, 6-month 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.
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).
Read the detailed description
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 MCI inadequately controlled with metformin monotherapy. The control group was treated with Gliclazide. We have 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 24 patients (12 patients for each arm) totally with the inclusion and exclusion criteria. The patients will be randomized at a 1:1 ratio into Henagliflozin 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 8-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.
- Being tested
- Henagliflozin, Gliclazide
- Keywords
- Functional MRI, Cognition, Olfactory function, Henagliflozin and Gliclazide
- Medical subject headings
- Diabetes Mellitus, Type 2, Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HenagliflozinDrug
Also called metformin
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.
GliclazideDrug
Also called metformin
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Gliclazide |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: from baseline to 16-week follow-up
Secondary outcomes (3)
Change of cognitive function
Type 2 diabetes mellitus patients with MCI were relieved of mild cognitive impairment , which means MoCA scores were not less than 26 points after treatment, or improved referring to the MoCA score or the RBANS total score increased by 0.5 standard deviation compared with baseline after treatment.
Measured: from baseline to 16-week follow-up
Olfactory threshold test
Whether the scores of olfactory threshold of the two groups after intervention were higher than those before treatment and the difference of changes between the two groups. Olfactory testing was performed using Olfactory Function Assessment by Computerized Testing (OLFACT) (Osmic Enterprises, Inc.). Based on the University of Pennsylvania Smell Identification Test (UPSIT), OLFACT tests were computerized, standardized, and self-administered. Threshold testing was performed by a series of binary dilutions of n-butanol solution in light mineral oil, and scores ranged from 1 to 13.5. Higher scores indicated better ability to detect odors.
Measured: from baseline to 16-week follow-up
Change of metabolism
The changes of glycosylated hemoglobin among the two groups before and after intervention. The level of glycosylated hemoglobin <7% means better glucose metabolism.
Measured: from baseline to 16-week follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Oct 2023
- Study start1 Apr 2024
- Primary completion30 Jun 2025
- Study completion30 Jun 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Type 2 Diabetes MellitusStudies of the same condition, open and under way.
- More trials run by The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical SchoolThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Zhu DaLong, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06085703
- Sponsor's protocol ID
- ZZ2023
- Status last verified
- Oct 2023
- First submitted
- 10 Oct 2023
- Last updated
- 10 Jul 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 31221697Zhang 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.
PubMed 29500313Cheng 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.
PubMed 35263425Chao Y, Jiao J, Zhang B, Sun J, Tong X, Yang H, Wu T, Zhang Z, Bi Y. Henagliflozin enhances frontal neural activation and cognitive function versus gliclazide in type 2 diabetes patients with mild cognitive impairment: A 16-week randomized controlled trial. J Endocrinol Invest. 2026 Apr;49(4):947-957. doi: 10.1007/s40618-025-02775-2. Epub 2026 Jan 31.
PubMed 41619161
Study at a glance
From the registry record, last updated by the sponsor on 10 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective, Randomized, Open Label, Parallel, 6-month 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.
- ClinicalTrials.gov ID
- NCT06085703
- Acronym / sponsor ID
- ZZ2023
- Keywords
- Functional MRI, Cognition, Olfactory function, Henagliflozin and Gliclazide
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical SchoolUniversity, hospital or other
- Study start
- 1 Apr 2024 (actual)
- Primary completion
- 30 Jun 2025 (actual)
- Study completion
- 30 Jun 2025 (actual)
- First posted
- 17 Oct 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
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 MCI inadequately controlled with metformin monotherapy. The control group was treated with Gliclazide. We have 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 24 patients (12 patients for each arm) totally with the inclusion and exclusion criteria. The patients will be randomized at a 1:1 ratio into Henagliflozin 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 8-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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Henagliflozin Group | Experimental | Drug: HenagliflozinHenagliflozin 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. |
| Gliclazide Group | Experimental | Drug: GliclazideGliclazide 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. |
Who may qualify
- Ages
- 55 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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%;
Key exclusion criteria (11 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HenagliflozinAlso: metforminHenagliflozin 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. | Drug | Henagliflozin Group |
| GliclazideAlso: metforminGliclazide 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. | Drug | Gliclazide Group |
Primary outcome
Change of olfactory brain activation by fMRI
Time frame: from baseline to 16-week follow-up
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.
3 secondary outcomes
Change of cognitive function
Time frame: from baseline to 16-week follow-up
Olfactory threshold test
Time frame: from baseline to 16-week follow-up
Change of metabolism
Time frame: from baseline to 16-week follow-up
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jul 2025.
- Background: PubMed 31221697Zhang 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.
- Background: PubMed 29500313Zhang 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.
- Background: PubMed 35263425Cheng 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.
- Derived from this study: PubMed 41619161Chao Y, Jiao J, Zhang B, Sun J, Tong X, Yang H, Wu T, Zhang Z, Bi Y. Henagliflozin enhances frontal neural activation and cognitive function versus gliclazide in type 2 diabetes patients with mild cognitive impairment: A 16-week randomized controlled trial. J Endocrinol Invest. 2026 Apr;49(4):947-957. doi: 10.1007/s40618-025-02775-2. Epub 2026 Jan 31.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Henagliflozin and Gliclazide in people with Type 2 Diabetes Mellitus and Mild Cognitive Impairment, run by The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change of olfactory brain activation by fMRI (time frame: from baseline to 16-week follow-up). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06085703, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jul 2025.