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

NCT06594172 | Not Yet Recruiting Phase 2

• 1 other identifier: GMUCR2024-01019
• Study Type: interventional
• Target: 67
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Radiation Disease; Cognitive Impairment; Drug Effect

Keywords

radiation induced brain injury; Memantine; Pioglitazone; cognitive function

Outcome Measures

Primary Outcomes (1)

• the cumulative incidence of cognitive failure

  the proportion of participants who experience cognitive impairments after radiation therapy

  At weeks 4, 8, 16, 24, 36, and 48 after the completion of radiotherapy

Secondary Outcomes (3)

• 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

Study Arms (1)

MPR

EXPERIMENTAL

combined Memantine and Pioglitazone with radiation therapy

Drug: Memantine Oral Tablet; Drug: Pioglitazone 15mg; Radiation: Hippocampal avoidance whole-brain radiotherapy (HA-WBRT)

Interventions

Memantine Oral Tablet DRUG

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.

Also known as: pioglitazone, hippocampal avoidance whole-brain radiotherapy (HA-WBRT)

MPR

Pioglitazone 15mg DRUG

Simultaneous oral administration of Pioglitazone Tablets (15mg/tablet): Weeks 1-24: 30mg once daily.

MPR

Hippocampal avoidance whole-brain radiotherapy (HA-WBRT) RADIATION

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).

MPR

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Affiliated Cancer Hospital & Institute of Guangzhou Medical University: lead
• Guangdong Provincial People's Hospital: collaborator
• Fujian Medical University Union Hospital: collaborator
• Southern Medical University, China: collaborator
• The Affiliated Panyu Center Hospital of Guangzhou Medical University: collaborator
• The Central Hospital of Shaoyang City: collaborator

MeSH Terms

Conditions

Abnormalities, Radiation-Induced; Cognitive Dysfunction

Interventions

Memantine; Pioglitazone

Condition Hierarchy (Ancestors)

Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Radiation Injuries; Wounds and Injuries; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Amantadine; Adamantane; Bridged-Ring Compounds; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Thiazolidinediones; Thiazoles; Sulfur Compounds; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: The Chair of the Department of Radiation Oncology

Study Record Dates

• First Submitted: September 10, 2024
• First Posted: September 19, 2024
• Study Start: September 10, 2024
• Primary Completion: December 30, 2025
• Study Completion (Estimated): June 30, 2027
• Last Updated: September 19, 2024

Record last verified: 2024-09