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.
Mild ischemic stroke, defined as a National Institutes of Health Stroke Scale (NIHSS) score ≤ 5.
Coexisting type 2 diabetes with a disease duration of less than 5 years.
Ability to complete the MoCA, MMSE, and the NINDS-CSN-recommended 1-hour standardized neuropsychological test for VCI.
Age between 40 and 75 years.
Coexisting dementia or severe cognitive impairment (MoCA < 17).
Coexisting severe depression, defined as a Hamilton Depression Rating Scale (HAMD) score ≥ 20.
Prior use of cognitive-enhancing drugs, such as donepezil or memantine.
Allergy to DPP4 inhibitors.
Parallel
Sentagliptin Phosphate - single dose
DrugSentagliptin 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.
Placebo
DrugPlacebo (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.
Change in MoCA score before and after the 180-day intervention
Change in MoCA score before and after the 180-day intervention
PSCI incidence at 180 days
MoCA score \< 25
Changes in MMSE score and scores in various cognitive domains before and after the 180-day intervention
Changes in MMSE score and scores in various cognitive domains before and after the 180-day intervention
Changes in MoCA and MMSE scores before and after the 90-day intervention
Changes in MoCA and MMSE scores before and after the 90-day intervention
Modified Rankin Scale (mRS) score and cardiovascular and cerebrovascular events at 90 and 180 days
Modified Rankin Scale (mRS) score and cardiovascular and cerebrovascular events at 90 and 180 days
Click on the lead sponsor to view all of their trials.
This trial is not recruiting at the moment. You can still explore other options:
