DPP4 Inhibitor Intervention on Post-stroke Cognitive Impairment in Ischemic Stroke Patients With Type 2 Diabetes

NCT ID: NCT07241897

Last Updated: 2025-11-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

312 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-12-15

Study Completion Date

2028-04-30

Brief Summary

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Post-stroke cognitive impairment (PSCI) increases the risk of disability and mortality in stroke patients, thereby exacerbating the disease burden of stroke. Type 2 diabetes is a major risk factor for PSCI, and stroke patients with type 2 diabetes have a higher risk of developing PSCI. Despite the high incidence and severe impact of PSCI, effective intervention methods are still lacking. Identifying safe and effective drugs to improve cognitive function in stroke patients and reduce the risk of PSCI, especially for those with type 2 diabetes, is of significant importance and could help reduce the burden of stroke.

Dipeptidyl peptidase-4 (DPP4) inhibitors are first-line antidiabetic drugs, and several studies have shown that DPP4 inhibitors provide benefits beyond glucose control, including significantly improving cognitive function in patients with type 2 diabetes or slowing the progression of cognitive impairment. Our previous research found a significant negative correlation between baseline plasma soluble DPP4 (sDPP4) levels and the 90-day PSCI risk in ischemic stroke patients. Moreover, some studies indicate that DPP4 inhibitors can increase plasma sDPP4 levels. Based on this, we hypothesize that DPP4 inhibitors could be effective for PSCI intervention and may improve cognitive function post-stroke.

This project aims to conduct a multicenter, randomized, double-blind, placebo-controlled study. We will include patients with mild ischemic stroke combined with type 2 diabetes and provide continuous intervention with DPP4 inhibitors or a placebo for 180 days. Cognitive function in both groups will be assessed before and after intervention to determine if DPP4 inhibitors can improve cognitive function and reduce the risk of PSCI in ischemic stroke patients with type 2 diabetes. Clinical blood samples and imaging data will also be used to preliminarily explore potential mechanisms.

Detailed Description

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Conditions

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Ischemic Stroke Diabete Mellitus

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Intervention Group: Sentagliptin Phosphate 50 mg, once daily, plus metformin hydrochloride extended-release tablets (50 mg, two or three times daily). If blood glucose is still not well-controlled, sulfonylurea drugs may be added as needed.
Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors
Centralized network-based randomization will be used, with matching based on study center, patient age, gender, and glycated hemoglobin levels at the time of randomization. A double-blind design will be implemented, with patients randomly assigned in a 1:1 ratio to either the DPP4 inhibitor intervention group or the placebo control group, with both researchers and patients unaware of the group assignments.

Study Groups

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Intervention Group

Sentagliptin Phosphate 50 mg, once daily, plus metformin hydrochloride extended-release tablets (50 mg, two or three times daily). If blood glucose is still not well-controlled, sulfonylurea drugs may be added as needed.

Group Type EXPERIMENTAL

Sentagliptin Phosphate - single dose

Intervention Type DRUG

Sentagliptin Phosphate 50 mg, once daily, plus metformin hydrochloride extended-release tablets (50 mg, two or three times daily). If blood glucose is still not well-controlled, sulfonylurea drugs may be added as needed.

Control Group

Placebo (identical in size, shape, color, appearance, and odor to Sentagliptin Phosphate, 50 mg, once daily) plus metformin hydrochloride extended-release tablets (50 mg, two or three times daily). If blood glucose is still not well-controlled, sulfonylurea drugs may be added as needed

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Placebo (identical in size, shape, color, appearance, and odor to Sentagliptin Phosphate, 50 mg, once daily) plus metformin hydrochloride extended-release tablets (50 mg, two or three times daily). If blood glucose is still not well-controlled, sulfonylurea drugs may be added as needed.

Interventions

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Sentagliptin Phosphate - single dose

Sentagliptin Phosphate 50 mg, once daily, plus metformin hydrochloride extended-release tablets (50 mg, two or three times daily). If blood glucose is still not well-controlled, sulfonylurea drugs may be added as needed.

Intervention Type DRUG

Placebo

Placebo (identical in size, shape, color, appearance, and odor to Sentagliptin Phosphate, 50 mg, once daily) plus metformin hydrochloride extended-release tablets (50 mg, two or three times daily). If blood glucose is still not well-controlled, sulfonylurea drugs may be added as needed.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Mild ischemic stroke, defined as a National Institutes of Health Stroke Scale (NIHSS) score ≤ 5.
2. Coexisting type 2 diabetes with a disease duration of less than 5 years.
3. Ability to complete the MoCA, MMSE, and the NINDS-CSN-recommended 1-hour standardized neuropsychological test for VCI.
4. Age between 40 and 75 years.
5. Onset of stroke within the last 2 weeks.
6. Glycated hemoglobin (HbA1c) between 6.5% and 8.5%.
7. More than 9 years of education.
8. Informed consent signed by the patient or their family.

Exclusion Criteria

1. Coexisting dementia or severe cognitive impairment (MoCA \< 17).
2. Coexisting severe depression, defined as a Hamilton Depression Rating Scale (HAMD) score ≥ 20.
3. Prior use of cognitive-enhancing drugs, such as donepezil or memantine.
4. Allergy to DPP4 inhibitors.
5. Past or current use of DPP4 inhibitors.
6. Past or current use of GLP-1 agonists.
7. Type 1 diabetes, latent autoimmune diabetes in adults, secondary diabetes, malignant tumors, autoimmune diseases, or other endocrine-related diseases.
8. Moderate or severe liver or kidney dysfunction.
9. Chronic or acute pancreatitis.
10. Pregnancy or lactation.
11. Severe infection or severely impaired immune response.
12. Participation in other clinical trials.
13. Past or current use of insulin therapy.
Minimum Eligible Age

40 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Second Affiliated Hospital of Soochow University

OTHER

Sponsor Role lead

Responsible Party

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yifang zhu

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Department of Neurology, Second Affiliated Hospital of Soochow University

Suzhou, Jiangsu, China

Site Status

Countries

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China

Central Contacts

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Shoujiang You, MD, PhD

Role: CONTACT

+8615995738506

WenYan Hua, MD

Role: CONTACT

0512-67783682

Facility Contacts

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Shoujiang You, MD, PhD

Role: primary

00 86 512 67783662

Yongjun Cao, MD, PhD

Role: backup

00 86 512 67784789

References

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You S, Bi Y, Miao M, Bao A, Du J, Xu T, Liu CF, Zhang Y, He J, Cao Y, Zhong C. Plasma sDPP4 (Soluble Dipeptidyl Peptidase-4) and Cognitive Impairment After Noncardioembolic Acute Ischemic Stroke. Stroke. 2023 Jan;54(1):113-121. doi: 10.1161/STROKEAHA.122.040798. Epub 2022 Dec 7.

Reference Type RESULT
PMID: 36475470 (View on PubMed)

You S, Miao M, Lu Z, Bao A, Du J, Che B, Xu T, Zhong C, Cao Y, Liu CF, Zhang Y, He J. Plasma Soluble Dipeptidyl Peptidase-4 and Risk of Major Cardiovascular Events After Ischemic Stroke: Secondary Analysis of China Antihypertensive Trial in Acute Ischemic Stroke (CATIS). Neurology. 2022 Aug 30;99(9):e925-e934. doi: 10.1212/WNL.0000000000200784. Epub 2022 Jun 2.

Reference Type RESULT
PMID: 35654589 (View on PubMed)

Baggio LL, Varin EM, Koehler JA, Cao X, Lokhnygina Y, Stevens SR, Holman RR, Drucker DJ. Plasma levels of DPP4 activity and sDPP4 are dissociated from inflammation in mice and humans. Nat Commun. 2020 Jul 28;11(1):3766. doi: 10.1038/s41467-020-17556-z.

Reference Type RESULT
PMID: 32724076 (View on PubMed)

Ma M, Hasegawa Y, Koibuchi N, Toyama K, Uekawa K, Nakagawa T, Lin B, Kim-Mitsuyama S. DPP-4 inhibition with linagliptin ameliorates cognitive impairment and brain atrophy induced by transient cerebral ischemia in type 2 diabetic mice. Cardiovasc Diabetol. 2015 May 20;14:54. doi: 10.1186/s12933-015-0218-z.

Reference Type RESULT
PMID: 25986579 (View on PubMed)

Chiazza F, Tammen H, Pintana H, Lietzau G, Collino M, Nystrom T, Klein T, Darsalia V, Patrone C. The effect of DPP-4 inhibition to improve functional outcome after stroke is mediated by the SDF-1alpha/CXCR4 pathway. Cardiovasc Diabetol. 2018 May 19;17(1):60. doi: 10.1186/s12933-018-0702-3.

Reference Type RESULT
PMID: 29776406 (View on PubMed)

Borzi AM, Condorelli G, Biondi A, Basile F, Vicari ESD, Buscemi C, Luca S, Vacante M. Effects of vildagliptin, a DPP-4 inhibitor, in elderly diabetic patients with mild cognitive impairment. Arch Gerontol Geriatr. 2019 Sep-Oct;84:103896. doi: 10.1016/j.archger.2019.06.001. Epub 2019 Jun 3.

Reference Type RESULT
PMID: 31204117 (View on PubMed)

Jeong SH, Kim HR, Kim J, Kim H, Hong N, Jung JH, Baik K, Cho H, Lyoo CH, Ye BS, Sohn YH, Seong JK, Lee PH. Association of Dipeptidyl Peptidase-4 Inhibitor Use and Amyloid Burden in Patients With Diabetes and AD-Related Cognitive Impairment. Neurology. 2021 Sep 14;97(11):e1110-e1122. doi: 10.1212/WNL.0000000000012534. Epub 2021 Aug 11.

Reference Type RESULT
PMID: 34380754 (View on PubMed)

Sun C, Xiao Y, Li J, Ge B, Chen X, Liu H, Zheng T. Nonenzymatic function of DPP4 in diabetes-associated mitochondrial dysfunction and cognitive impairment. Alzheimers Dement. 2022 May;18(5):966-987. doi: 10.1002/alz.12437. Epub 2021 Aug 10.

Reference Type RESULT
PMID: 34374497 (View on PubMed)

Zhong J, Maiseyeu A, Davis SN, Rajagopalan S. DPP4 in cardiometabolic disease: recent insights from the laboratory and clinical trials of DPP4 inhibition. Circ Res. 2015 Apr 10;116(8):1491-504. doi: 10.1161/CIRCRESAHA.116.305665.

Reference Type RESULT
PMID: 25858071 (View on PubMed)

Mulvihill EE, Drucker DJ. Pharmacology, physiology, and mechanisms of action of dipeptidyl peptidase-4 inhibitors. Endocr Rev. 2014 Dec;35(6):992-1019. doi: 10.1210/er.2014-1035. Epub 2014 Sep 12.

Reference Type RESULT
PMID: 25216328 (View on PubMed)

Levine DA, Wadley VG, Langa KM, Unverzagt FW, Kabeto MU, Giordani B, Howard G, Howard VJ, Cushman M, Judd SE, Galecki AT. Risk Factors for Poststroke Cognitive Decline: The REGARDS Study (Reasons for Geographic and Racial Differences in Stroke). Stroke. 2018 Apr;49(4):987-994. doi: 10.1161/STROKEAHA.117.018529. Epub 2018 Mar 16.

Reference Type RESULT
PMID: 29581343 (View on PubMed)

Rost NS, Brodtmann A, Pase MP, van Veluw SJ, Biffi A, Duering M, Hinman JD, Dichgans M. Post-Stroke Cognitive Impairment and Dementia. Circ Res. 2022 Apr 15;130(8):1252-1271. doi: 10.1161/CIRCRESAHA.122.319951. Epub 2022 Apr 14.

Reference Type RESULT
PMID: 35420911 (View on PubMed)

Provided Documents

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Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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82471226

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

LC2024019

Identifier Type: -

Identifier Source: org_study_id

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