Effects of DL-3-n-butylphthalide on Chemotherapy-Induced Cognitive Impairment

Official title

Effects of DL-3-n-butylphthalide on Chemotherapy-Induced Cognitive Impairment (NBP CICI)：a Prospective, Randomized, Double Blinded, Multicenter, Placebo Controlled Study

Overview

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.

Interventions

• Drug DL-3-n-butylphthalide
  Take butylphthalide soft capsules orally
• Drug Empty Medication Capsules
  Take empty medication capsules orally

Primary outcome measures

• Mini-mental State Examination (MMSE) [Time frame: 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) [Time frame: 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 (9)

• Clinician's Interview-based Impression of Change plus caregiver input(CIBIC-plus) [Time frame: 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) [Time frame: 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) [Time frame: 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) [Time frame: 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) [Time frame: 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) [Time frame: 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) [Time frame: 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) [Time frame: 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) [Time frame: 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)]

Eligibility criteria

Inclusion criteria

• Treatment with paclitaxel drugs (such as paclitaxel/docetaxel/albumin-based paclitaxel, etc.) or platinum-based chemotherapy (cisplatin), and not combined with other chemotherapy drugs; (Cancer type is not limited)
• Sign the informed consent and understand the purpose and significance of the study;
• Aged between 35 and 80 years old;
• Ability to complete the questionnaire on their own or with assistance;
• Complaints of cognitive impairment involving memory and/or other cognitive areas lasting for at least 3 months;
• Cancer treatment has been completed and is considered curable, with the exception of endocrine therapy after chemotherapy;
• MMSE score: 18-26;
• Clinical Dementia Rating (CDR) score: 0.5-2;
• Fluent in Chinese;
• No visual or hearing impairment;
• Did not participate in another intervention study within 6 months prior to commencing this study;

Exclusion criteria

• Diagnosed with a cognitively impaired disease, such as Alzheimer's disease;
• Patients will be excluded from fMRI testing if they are claustrophobic, have MRI contraindications such as pacemakers or metal implants, and patients who did not undergo fMRI testing may still participate in clinical trials if all other enrollment criteria are met;
• Take medications that may affect cognitive function
• History of brain metastases or other brain tumors;
• History of stroke or severe head trauma;
• History of epilepsy or other seizures;
• Pregnant or considering becoming pregnant;
• Any active nervous system or untreated/unremitted mental disorder (such as active major depressive disorder or other major mental disorder described in the DSM-5, allowing treatment of depression if treatment is stable)
• Any history of alcohol or drug abuse or dependence within the past 2 years;
• Any major systemic disease or unstable medical condition that may cause difficulty in complying with the protocol, including: a history of myocardial infarction or instability in the past year, serious cardiovascular disease (including angina or congestive heart failure with resting symptoms, or clinically significant abnormalities in the electrocardiogram), clinically significant and/or unstable lung, gastrointestinal, liver or kidney disease;
• Have taken any non-research drugs to improve cognitive function within 4 weeks prior to enrollment;
• Have taken butylphthalein in the past 30 days.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT06508671 · NBP-CICI-202405

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗