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

Phase 2

Not yet recruiting

• Conditions: Radiation Disease; Cognitive Impairment; Drug Effect
• Interventions: Drug: Memantine Oral Tablet; Drug: Pioglitazone 15mg; Radiation: Hippocampal avoidance whole-brain radiotherapy (HA-WBRT)

• Registration Number: NCT06594172
• Lead Sponsor: Affiliated Cancer Hospital & Institute of Guangzhou Medical University

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2024-09
• Study Start: 2024-09-10
• Study First Submitted: 2024-09-10
• Study First Submitted QC: 2024-09-10
• Study First Posted: 2024-09-13
• Last Update Submitted: 2024-09-16
• Last Update Posted: 2024-09-19
• Primary Completion: 2025-12-30
• Study Completion: 2027-06-30

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 67

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
MPR	Pioglitazone 15mg	combined Memantine and Pioglitazone with radiation therapy
MPR	Memantine Oral Tablet	combined Memantine and Pioglitazone with radiation therapy
MPR	Hippocampal avoidance whole-brain radiotherapy (HA-WBRT)	combined Memantine and Pioglitazone with radiation therapy

Primary Outcome Measures

Name	Time	Method
the cumulative incidence of cognitive failure	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

Secondary Outcome Measures

Name	Time	Method
Cognitive Score Decline	At weeks 4, 8, 16, 24, 36, and 48 after the completion of radiotherapy	based on the Reliable Change Index of at least one cognitive test
Progressive-free survival for Intracranial Tumors	At weeks 4, 8, 16, 24, 36, and 48 after the completion of radiotherapy	latencies to the first intracranial treatment failure or death from any cause
Overall Survival	At weeks 4, 8, 16, 24, 36, and 48 after the completion of radiotherapy	death due to any cause