Clinical trial NCT06594172: Early Application of Memantine and Pioglitazone to Protect Cognitive Function After Radiotherapy
Official title: A Phase II Clinical Trial of of Early Application of Memantine and Pioglitazone to Protect Cognitive Function After Radiotherapy
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Radiation Disease
Cognitive Impairment
Drug Effect
Keywords: radiation induced brain injury
Memantine
Pioglitazone
cognitive function
Lead sponsor: Affiliated Cancer Hospital & Institute of Guangzhou Medical University
Sponsor class: OTHER
Collaborators: name: Guangdong Provincial People's Hospital
name: Fujian Medical University Union Hospital
name: Southern Medical University, China
name: The Affiliated Panyu Center Hospital of Guangzhou Medical University
name: The Central Hospital of Shaoyang City
First posted: 2024-09-19
Enrollment: 67
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: the cumulative incidence of cognitive failure
timeFrame: At weeks 4, 8, 16, 24, 36, and 48 after the completion of radiotherapy
Secondary outcomes:
measure: Cognitive Score Decline
timeFrame: At weeks 4, 8, 16, 24, 36, and 48 after the completion of radiotherapy
measure: Progressive-free survival for Intracranial Tumors
timeFrame: At weeks 4, 8, 16, 24, 36, and 48 after the completion of radiotherapy
measure: Overall Survival
timeFrame: At weeks 4, 8, 16, 24, 36, and 48 after the completion of radiotherapy
Other outcomes:
Locations:
Study officials:
References: