Radiation DiseasePhase 2NCT06594172
Early Application of Memantine and Pioglitazone to Protect Cognitive Function After Radiotherapy
A Phase 2 study testing Memantine Oral Tablet, Pioglitazone 15mg and Hippocampal avoidance whole-brain radiotherapy (HA-WBRT) in people with Radiation Disease and Cognitive Impairment, run by Affiliated Cancer Hospital & Institute of Guangzhou Medical University.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Radiation Disease, Cognitive Impairment, Drug Effect
- What is being tested?
- Memantine Oral Tablet, Pioglitazone 15mg and Hippocampal avoidance whole-brain radiotherapy (HA-WBRT)
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 67 participants
- Where
- No sites listed yet
- Study dates
- 10 Sep 2024to 30 Jun 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
About this study
Official title: A Phase II Clinical Trial of of Early Application of Memantine and Pioglitazone to Protect Cognitive Function After Radiotherapy
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.
Read more
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
- Being tested
- Memantine Oral Tablet, Pioglitazone 15mg, Hippocampal avoidance whole-brain radiotherapy (HA-WBRT)
- Keywords
- radiation induced brain injury, Memantine, Pioglitazone, cognitive function
- Medical subject headings
- Abnormalities, Radiation-Induced, Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Memantine Oral TabletDrug
Also called pioglitazone, hippocampal avoidance whole-brain radiotherapy (HA-WBRT)
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.
Pioglitazone 15mgDrug
Simultaneous oral administration of Pioglitazone Tablets (15mg/tablet):
Weeks 1-24: 30mg once daily.
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).
| Study group | Role | What they receive |
|---|---|---|
| MPR | Experimental | combined Memantine and Pioglitazone with radiation therapy Receives: Drug: Memantine Oral Tablet; Drug: Pioglitazone 15mg; Radiation: Hippocampal avoidance whole-brain radiotherapy (HA-WBRT) |
What is being measured
The primary outcome is the main question the study is designed to answer.
the cumulative incidence of cognitive failure
the proportion of participants who experience cognitive impairments after radiation therapy
Measured: At weeks 4, 8, 16, 24, 36, and 48 after the completion of radiotherapy
Secondary outcomes (3)
Cognitive Score Decline
based on the Reliable Change Index of at least one cognitive test
Measured: 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
Measured: At weeks 4, 8, 16, 24, 36, and 48 after the completion of radiotherapy
Overall Survival
death due to any cause
Measured: At weeks 4, 8, 16, 24, 36, and 48 after the completion of radiotherapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2024
- Study start10 Sep 2024 (estimated)
- Primary completion30 Dec 2025 (estimated)
- Study completion30 Jun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Radiation DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 67 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Affiliated Cancer Hospital & Institute of Guangzhou Medical University
- Sponsor type
- University, hospital or other
- 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
- Principal investigator, Yuan yawei, Affiliated Cancer Hospital & Institute of Guangzhou Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06594172
- Sponsor's protocol ID
- GMUCR2024-01019
- Status last verified
- Sep 2024
- First submitted
- 10 Sep 2024
- Last updated
- 19 Sep 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Clinical Trial of of Early Application of Memantine and Pioglitazone to Protect Cognitive Function After Radiotherapy
- ClinicalTrials.gov ID
- NCT06594172
- Acronym / sponsor ID
- GMUCR2024-01019
- Conditions
- Radiation Disease, Cognitive Impairment, Drug Effect
- Keywords
- radiation induced brain injury, Memantine, Pioglitazone, cognitive function
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 67 participants (estimated)
- Lead sponsor
- Affiliated Cancer Hospital & Institute of Guangzhou Medical UniversityUniversity, hospital or other
- 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
- Study start
- 10 Sep 2024 (estimated)
- Primary completion
- 30 Dec 2025 (estimated)
- Study completion
- 30 Jun 2027 (estimated)
- First posted
- 19 Sep 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| MPR | Experimental | Drug: Memantine Oral Tablet, Drug: Pioglitazone 15mg, Radiation: Hippocampal avoidance whole-brain radiotherapy (HA-WBRT)combined Memantine and Pioglitazone with radiation therapy |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (8 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Memantine Oral TabletAlso: pioglitazone, hippocampal avoidance whole-brain radiotherapy (HA-WBRT)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 | MPR |
| Pioglitazone 15mgSimultaneous oral administration of Pioglitazone Tablets (15mg/tablet): Weeks 1-24: 30mg once daily. | Drug | MPR |
| 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). | Radiation | MPR |
Primary outcome
the cumulative incidence of cognitive failure
Time frame: 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
3 secondary outcomes
Cognitive Score Decline
Time frame: At weeks 4, 8, 16, 24, 36, and 48 after the completion of radiotherapy
Progressive-free survival for Intracranial Tumors
Time frame: At weeks 4, 8, 16, 24, 36, and 48 after the completion of radiotherapy
Overall Survival
Time frame: At weeks 4, 8, 16, 24, 36, and 48 after the completion of radiotherapy
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Memantine Oral Tablet, Pioglitazone 15mg and Hippocampal avoidance whole-brain radiotherapy (HA-WBRT) in people with Radiation Disease and Cognitive Impairment, run by Affiliated Cancer Hospital & Institute of Guangzhou Medical University.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 19 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
the cumulative incidence of cognitive failure (time frame: At weeks 4, 8, 16, 24, 36, and 48 after the completion of radiotherapy). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2024.