Effects of DL-3-n-butylphthalide on Chemotherapy-Induced Cognitive Impairment
NCT Number: NCT06508671
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE4
Conditions: Chemotherapy-Related Cognitive Impairment|DL-3-n-butylphthalide
Interventions: DRUG: DL-3-n-butylphthalide|DRUG: Empty Medication Capsules
Sponsor: First Hospital of China Medical University
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 100
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: TRIPLE (PARTICIPANT, INVESTIGATOR, OUTCOMES_ASSESSOR)|Primary Purpose: TREATMENT
Start Date: 2024-07
Completion Date: 2026-12

Summary:
Chemotherapy-related cognitive Impairment (CICI) is a series of neurocognitive deficits experienced during and after cancer chemotherapy. Studies have reported that CICI affects 25% to 75% of survivors and can persist for years after chemotherapy is discontinued, causing more severe progressive manifestations and placing a heavy burden on families and society. Numerous studies have proposed several potential mechanisms and etiologies for CICI, including direct neurotoxicity, disruption of the blood-brain barrier, reduced hippocampal neurogenesis, white matter abnormalities, secondary neuroinflammatory responses, and increased oxidative stress. At present, there is no clear and effective diagnosis and therapy for CICI, and how to diagnose and treat cognitive impairment caused by chemotherapy effectively is still the focus and difficulty.

Based on the previous consensus on the application of dl-3-n-butylphthalide, butylphthalein can play a neuroprotective role by reducing oxidative stress and inflammatory response, inhibiting neuronal apoptosis, improving mitochondrial function and other mechanisms, and significantly improve the performance of the central nervous system caused by cerebral ischemia and vascular dementia. However, the increase of neuroinflammatory response and oxidative stress is precisely one of the potential mechanisms of CICI pathogenesis. Therefore, based on the above findings, this study hypothesized that dl-3-n-butylphthalide would also have considerable efficacy in the treatment of CICI.

Primary Outcome Measures: Mini-mental State Examination (MMSE), The scale ranges from 0 to 30 points. Test scores are closely related to literacy level, and the normal cut-off values are: illiterate \>17 points, primary \>20 points, junior high school and above \>24 points. Combined with the basic characteristics of patients, preoperative and post-chemotherapy assessment was performed to determine the dementia status of patients., Before chemotherapy,during chemotherapy (12 week after the start of chemotherapy,24 week after the start of chemotherapy),after chemotherapy (12 days after the last chemotherapy)|Montreal Cognitive Assessment (MoCA), Patients' cognitive domains were assessed with 11 test items in eight cognitive domains: attention and concentration, executive function, memory, language, visual structure skills, abstract thinking, computation, and orientation. Total score 30, ≥26 normal. Combined with the basic characteristics of patients, preoperative and post-chemotherapy assessment was performed to determine the status of patients with mild cognitive impairment., Before chemotherapy,during chemotherapy (12 week after the start of chemotherapy,24 week after the start of chemotherapy),after chemotherapy (12 days after the last chemotherapy)
Secondary Outcome Measures: Clinician's Interview-based Impression of Change plus caregiver input(CIBIC-plus), CIBIC-plus reflects the clinical improvement of the subject through interviews with the subject and their caregivers., Before chemotherapy,during chemotherapy (12 week after the start of chemotherapy,24 week after the start of chemotherapy),after chemotherapy (12 days after the last chemotherapy)|Clinical Dementia Rating(CDR), CDR is a multidimensional dementia severity scale, scored on a 0-3 scale, with higher scores indicating poorer functioning., Before chemotherapy,during chemotherapy (12 week after the start of chemotherapy,24 week after the start of chemotherapy),after chemotherapy (12 days after the last chemotherapy)|Activities of Daily Living (ADL), ADL are used to assess a patient's ability to perform daily living., Before chemotherapy,during chemotherapy (12 week after the start of chemotherapy,24 week after the start of chemotherapy),after chemotherapy (12 days after the last chemotherapy)|Hamilton Depression Scale(HAMD), HAMD is used to assess the severity and progression of depressive symptoms., Before chemotherapy,during chemotherapy (12 week after the start of chemotherapy,24 week after the start of chemotherapy),after chemotherapy (12 days after the last chemotherapy)|Hamilton Anxiety Scale(HAMA), HAMA is mainly used to assess the severity of neurosis and other anxiety symptoms in patients., Before chemotherapy,during chemotherapy (12 week after the start of chemotherapy,24 week after the start of chemotherapy),after chemotherapy (12 days after the last chemotherapy)|Self-rating depression scale(SDS), SDS is mainly suitable for adults with depressive symptoms, and can intuitively reflect the subjective feelings of depressed patients., Before chemotherapy,during chemotherapy (12 week after the start of chemotherapy,24 week after the start of chemotherapy),after chemotherapy (12 days after the last chemotherapy)|self-rating anxiety scale(SAS), SAS is mainly suitable for adults with anxiety symptoms and can directly reflect the subjective feelings of patients with anxiety., Before chemotherapy,during chemotherapy (12 week after the start of chemotherapy,24 week after the start of chemotherapy),after chemotherapy (12 days after the last chemotherapy)|Functional Magnetic Resonance Imaging(fMRI), fMRI is a research method that stimulates specific senses to cause neural activity (functional area activation) in the corresponding parts of the cerebral cortex and shows it through magnetic resonance images., Before chemotherapy,during chemotherapy (12 week after the start of chemotherapy,24 week after the start of chemotherapy),after chemotherapy (12 days after the last chemotherapy)|Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE), PRO-CTCAE is a tool used to document self-reported adverse events and their severity on a 5-point scale. In our trial, we plan to evaluate 12 symptoms selected from the original PRO-CTCAE scale, specifically decreased appetite, nausea, vomiting, heartburn, bloating, constipation, diarrhea, abdominal pain, insomnia, fatigue, headache, and dizziness., Before chemotherapy,during chemotherapy (12 week after the start of chemotherapy,24 week after the start of chemotherapy),after chemotherapy (12 days after the last chemotherapy)