NCT06594172

Early Application of Memantine and Pioglitazone to Protect Cognitive Function After Radiotherapy

A Phase II Clinical Trial of of Early Application of Memantine and Pioglitazone to Protect Cognitive Function After Radiotherapy

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 67 (estimated)
• Sponsor: Affiliated Cancer Hospital & Institute of Guangzhou Medical University · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Radiation Disease
• Cognitive Impairment
• Drug Effect

Interventions

Type	Name	Description
DRUG	Memantine Oral Tablet	Oral administration of Memantine Tablets (10mg/tablet): Week 1: 5mg in the morning. Week 2: 5mg twice daily. Week 3: 10mg in the morning, 5mg in the evening. Weeks 4-24: 10mg twice daily.
DRUG	Pioglitazone 15mg	Simultaneous oral administration of Pioglitazone Tablets (15mg/tablet): Weeks 1-24: 30mg once daily.
RADIATION	Hippocampal avoidance whole-brain radiotherapy (HA-WBRT)	Based on the RTOG 0933 protocol, hippocampal and perihippocampal regions are delineated, and hippocampal dose constraints are applied. The radiation dose to the perihippocampal region is determined based on the size, number, and volume of brain metastases (whole-brain radiation therapy: DT 30Gy/10F, weeks 1-2; with a simultaneous boost to the pathological local area if necessary, 10-20Gy).

Timeline

• Start date: 2024-09-10
• Primary completion: 2025-12-30
• Completion: 2027-06-30
• First posted: 2024-09-19
• Last updated: 2024-09-19