Not yet recruitingNCT06594172Updated Sep 19, 2024

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

A Phase 2 interventional study of Memantine Oral Tablet and Pioglitazone 15mg in Radiation Disease, Cognitive Impairment and Drug Effect, sponsored by Affiliated Cancer Hospital & Institute of Guangzhou Medical University. Not yet recruiting. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2024-09-19.

Sponsored by Affiliated Cancer Hospital & Institute of Guangzhou Medical University · Phase 2, Interventional, and Treatment

From the registry’s dates

Primary completion was expected by Dec 2025, 9 months ago, but the record still lists the study as not yet recruiting.

Phase: Phase 2
Study type: Interventional
Enrollment: 67
Allocation: Not applicable
Ages: 18 Years to 65 Years
Sex: All

Study 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 studied

Radiation Disease
Cognitive Impairment
Drug Effect

Browse trials for

Cognitive Dysfunction 3,842

Keywords

radiation induced brain injury
Memantine
Pioglitazone
cognitive function

In context

Cognitive Dysfunction

3,842 studies on the registry are indexed under Cognitive Dysfunction; 1,099 are open to participants now.

This study's planned enrollment of 67 is close to the median of 65 across 2,807 interventional studies indexed under Cognitive Dysfunction.

Browse Cognitive Dysfunction studies →

Lead sponsor

Affiliated Cancer Hospital & Institute of Guangzhou Medical University is the lead sponsor of 28 studies on the registry; 15 are open to participants now.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years to 65 Years
Sexes eligible: All
Accepts healthy volunteers: No

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

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

Phase: Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrollment: 67 participants (estimated)

Study arms

Experimental
MPR
combined Memantine and Pioglitazone with radiation therapy
Drug: Memantine Oral Tablet · Drug: Pioglitazone 15mg · Radiation: Hippocampal avoidance whole-brain radiotherapy (HA-WBRT)

Interventions

DrugMemantine 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.
Also known as: pioglitazone, hippocampal avoidance whole-brain radiotherapy (HA-WBRT)
DrugPioglitazone 15mg
Simultaneous oral administration of Pioglitazone Tablets (15mg/tablet): Weeks 1-24: 30mg once daily.
RadiationHippocampal 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).

What researchers measure

Primary outcomes

the cumulative incidence of cognitive failure
the proportion of participants who experience cognitive impairments after radiation therapy
Time frame: At weeks 4, 8, 16, 24, 36, and 48 after the completion of radiotherapy

Secondary outcomes

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

Study locations

No study locations are listed for this record.

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Sep 19, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT06594172
Lead sponsor: Affiliated Cancer Hospital & Institute of Guangzhou Medical University
Collaborators: Guangdong Provincial People's Hospital, Fujian Medical University Union Hospital, Southern Medical University, China, The Affiliated Panyu Center Hospital of Guangzhou Medical University, The Central Hospital of Shaoyang City
Responsible party: Yuan yawei (The Chair of the Department of Radiation Oncology, Affiliated Cancer Hospital & Institute of Guangzhou Medical University) — Principal investigator
First posted: Sep 19, 2024
Start date: Sep 10, 2024 (estimated)
Primary completion: Dec 30, 2025 (estimated)
Completion: Jun 30, 2027 (estimated)
Last update: Sep 19, 2024

Oversight

FDA-regulated drug: No
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is not yet recruiting, as verified in Sep 2024. You cannot join it, but the record below documents what was studied.

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