A Phase II Clinical Trial of of Early Application of Memantine and Pioglitazone to Protect Cognitive Function After Radiotherapy
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 67
- 主要终点
- the cumulative incidence of cognitive failure
研究概览
简要总结
This clinical trial aims to evaluate the efficacy of early intervention with Memantine and Pioglitazone in preventing Radiation-Induced Brain Injury (RIBI) in patients undergoing cranial radiotherapy.
RIBI, a significant complication of radiation therapy for primary and metastatic brain tumors, as well as head and neck cancers, often presents with delayed and irreversible neurological damage, severely affecting patients' quality of life.
Our previous studies have indicated that Memantine, an NMDAR antagonist, and Pioglitazone, a PPAR-γ agonist, play crucial roles in modulating the neuroprotective immune microenvironment by targeting key mechanisms of neuron-astrocyte fatty acid metabolism coupling. These findings suggest that early administration of these drugs could protect cognitive function and reduce neuroinflammation in patients post-radiation.
This prospective phase II clinical trial will assess the combined efficacy of Memantine and Pioglitazone in improving cognitive outcomes and preventing RIBI without adversely impacting the anti-tumor efficacy of radiation therapy. The study will also explore the synergistic effects of these two FDA-approved drugs in early-stage RIBI prevention, providing a new therapeutic strategy for enhancing the quality of life in cancer patients receiving radiotherapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Recursive Partitioning Analysis (RPA), Class I ~ Class II
- •Karnofsky Performance Status of ≥70
- •The primary tumor must be pathologically confirmed. For newly diagnosed brain metastases, the number of metastases is not limited, but the brain metastases could not have been within 5 mm of hippocampus. Additionally, there must be no hard or soft meningeal metastases.
- •No history of whole-brain radiation therapy; patients who are eligible for surgical resection of brain metastases prior to radiation therapy are allowed.
- •Bone marrow function: White blood cell count ≥ 4 × 10⁹/L, hemoglobin ≥ 90 g/L, and platelet count ≥ 100 × 10⁹/L.
- •Adequate hepatic function: Total bilirubin ≤ 1.5 × ULN (Upper Limit of Normal); ALT (alanine aminotransferase), AST (aspartate aminotransferase) ≤ 2.5 × ULN; ALP (alkaline phosphatase) ≤ 2.5 × ULN and total bilirubin ≤ ULN.
- •Adequate renal function: creatinine clearance rate ≥ 30 ml/min.
- •Patients or their legal guardians voluntarily participate and sign the informed consent form.
排除标准
- •Radiographic evidence of hydrocephalus or other architectural distortion of the ventricular system, including placement of external ventricular drain or ventriculoperitoneal shunt.
- •Planned cytotoxic chemotherapy during the WBRT.
- •Pregnant or lactating women (Women of childbearing age must undergo a pregnancy test; effective contraception must be enforced during the treatment period).
- •Previous cranial radiation therapy (Except for patients with head and neck cancer where the disease site is outside the cranial radiation field).
- •Severe or active symptomatic cardiopulmonary diseases; clinically significant psychiatric disorders; Personality or psychiatric disease; Severe hepatic disease defined as a diagnosis of Child-Pugh class B or C hepatic disease;
- •Intolerant to or allergic to Memantine or pioglitazone.
- •Difficulty swallowing, chronic diarrhea, or bowel obstruction.
- •NYHA class III or IV heart failure or symptomatic peripheral edema (grade 2 or higher); those treated with insulin or oral hypoglycemic agents for steroid-induced hyperglycemia, or those currently using other NMDA antagonists.
研究组 & 干预措施
MPR
combined Memantine and Pioglitazone with radiation therapy
干预措施: Memantine Oral Tablet (Drug)
MPR
combined Memantine and Pioglitazone with radiation therapy
干预措施: Pioglitazone 15mg (Drug)
MPR
combined Memantine and Pioglitazone with radiation therapy
干预措施: Hippocampal avoidance whole-brain radiotherapy (HA-WBRT) (Radiation)
结局指标
主要结局
the cumulative incidence of cognitive failure
时间窗: At weeks 4, 8, 16, 24, 36, and 48 after the completion of radiotherapy
the proportion of participants who experience cognitive impairments after radiation therapy
次要结局
- Cognitive Score Decline(At weeks 4, 8, 16, 24, 36, and 48 after the completion of radiotherapy)
- Progressive-free survival for Intracranial Tumors(At weeks 4, 8, 16, 24, 36, and 48 after the completion of radiotherapy)
- Overall Survival(At weeks 4, 8, 16, 24, 36, and 48 after the completion of radiotherapy)
研究者
Yuan yawei
The Chair of the Department of Radiation Oncology
Affiliated Cancer Hospital & Institute of Guangzhou Medical University