Memantine Hydrochloride for Subdural Hematoma

(TASD Trial)

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of New Mexico

Must not be taking: NMDA antagonists, Acetylcholinesterase inhibitors

Disqualifiers: Severe renal impairment, Severe hepatic impairment, others

Compensation: Varies

Number of Visits: 1

Duration: 7 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether Memantine Hydrochloride can improve recovery after surgery for chronic subdural hematoma (cSDH), a condition where fluid collects on the brain and often requires surgery. Many patients experience issues like weakness or confusion post-surgery, possibly due to temporary brain activity disruptions called spreading depolarizations (SD). The trial aims to determine if Memantine can reduce these issues and aid recovery. Participants who recently underwent surgery for cSDH and have electrodes placed for monitoring might be suitable candidates. The trial includes two groups: one receiving Memantine and the other receiving a placebo (a look-alike with no active drug). As an Early Phase 1 trial, this research focuses on understanding how Memantine works in people, offering participants a chance to contribute to groundbreaking medical knowledge.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you cannot participate if you are using NMDA antagonists or acetylcholinesterase inhibitors. If you are on these medications, you would need to stop them to join the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that memantine is usually well-tolerated. Studies have found that those taking memantine often experience only mild side effects, such as dizziness, headache, or constipation.

Other research has examined memantine's impact on brain recovery. Patients using memantine had better outcomes with few negative effects. This suggests that while memantine undergoes testing for new purposes, previous studies already support its safety in humans.

Since this trial is in its early stages, it aims to gather initial safety data. Although memantine has shown safety in other contexts, this study will provide more specific information about its use for subdural hematoma. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for subdural hematoma, which typically involve surgical intervention and supportive care, Memantine Hydrochloride presents a novel approach by potentially offering neuroprotective effects. Memantine is unique because it acts as an NMDA receptor antagonist, which may help reduce brain damage and improve recovery by protecting nerve cells from excessive stimulation. Researchers are excited about this treatment as it could provide a non-surgical option that enhances patient outcomes and recovery times. Additionally, its oral administration makes it an accessible and easy-to-use alternative for patients.

What evidence suggests that Memantine Hydrochloride might be an effective treatment for chronic subdural hematoma?

Research has shown that memantine, which participants in this trial may receive, might aid brain recovery after spreading depolarizations (SD), waves that can cause temporary neurological issues. One study found that memantine improved recovery in brain tissue and suggested similar benefits in real-life medical settings. Memantine protects the brain by blocking NMDA receptors, which play a role in SD. This action might reduce neurological problems after procedures like brain surgery. Early findings from other situations, such as radiation therapy for brain tumors, have provided safety and effectiveness data, indicating potential benefits in reducing problems with thinking or memory. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

This trial is for adults aged 18-100 who've had surgery for chronic subdural hematoma and experienced spreading depolarization within 48 hours post-operation. They must have an electrode strip placed during surgery. It's not for those with severe liver or kidney issues, known allergies to memantine, current memantine users, women not using dual contraception, or patients needing large craniotomy.

Inclusion Criteria

I have had surgery for a slow bleeding in my brain.

I had an electrode strip placed during surgery for seizure monitoring.

My surgical site infection was identified within 2 days after surgery.

Exclusion Criteria

You are allergic to memantine.

I cannot eat or receive food through a tube.

I am taking medication for memory or muscle control.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Surgery and Initial Monitoring

Subjects undergo surgery for chronic or subacute subdural hematoma and are monitored for spreading depolarizations and seizures using a recording electrode placed during surgery.

1-2 days

Inpatient monitoring

Treatment

Subjects with detected spreading depolarization are randomized to receive either memantine or placebo for 7 days.

7 days

Daily administration (inpatient)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of neurological deficits and adverse events.

90 days

Periodic follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• Memantine Hydrochloride
• Placebo

Trial Overview The TASD study is testing if Memantine Hydrochloride can reduce neurological problems like weakness or confusion after cSDH surgery by blocking certain brain signals (NMDA-R antagonism). Some participants will get the real drug while others a placebo to compare outcomes.

How Is the Trial Designed?

Group I: Memantine Experimental Treatment 1 Intervention

Subjects will be given memantine 10mg PO/ NG BID for 7 days

Group II: Placebo Placebo Group 1 Intervention

Subjects will be given identical placebo syrup PO/NG BID for 7 days

Who Is Running the Clinical Trial?

University of New Mexico

Lead Sponsor

Trials

393

Recruited

3,526,000+

Published Research Related to This Trial

Memantine, while generally well-tolerated for neurocognitive protection during cranial radiotherapy, can cause altered mental status, as demonstrated in a case involving an 18-year-old male with medulloblastoma who required ICU admission after starting the medication.

The patient's symptoms improved significantly after memantine was withheld, highlighting the need for clinicians to be cautious and monitor for potential neurocognitive side effects when prescribing memantine, especially in pediatric patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Life-threatening altered mental status secondary to memantine in an adolescent undergoing cranial radiotherapy for medulloblastoma. Kim, KN., Shah, YB., Croy, C., et al.[2023]

A review of cardiovascular adverse drug reactions (ADRs) associated with memantine identified 36 cases, including 18 reports of bradycardia, indicating a potential link between memantine and heart-related side effects.

Most cases of bradycardia resolved after discontinuing memantine, suggesting that while memantine may cause cardiac ADRs, the exact mechanism behind these effects is still not well understood.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does memantine induce bradycardia? A study in the French PharmacoVigilance Database. Gallini, A., Sommet, A., Montastruc, JL.[2013]

Memantine is an FDA-approved treatment for moderate to severe Alzheimer's disease, demonstrating both safety and efficacy as a standalone therapy or in combination with cholinesterase inhibitors.

Research suggests that memantine may also have potential therapeutic effects in other neuropsychiatric conditions, warranting further investigation into its broader applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Memantine: a review of studies into its safety and efficacy in treating Alzheimer's disease and other dementias. Thomas, SJ., Grossberg, GT.[2022]

Memantine, used for treating moderate to severe Alzheimer's disease, has been shown to have a favorable safety and tolerability profile, with adverse events similar in frequency to those experienced by patients on placebo, based on data from 2311 patients in six trials lasting at least 24 weeks.

The analysis indicates that both short- and long-term treatment with memantine is safe, with minimal adverse effects, and discontinuation rates due to side effects were comparable between memantine and placebo groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Memantine for the treatment of Alzheimer's disease: tolerability and safety data from clinical trials. Farlow, MR., Graham, SM., Alva, G.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9938764/

Memantine improves recovery after spreading ... The present study tested the hypothesis that memantine improves recovery of brain slices after SD and also explored the effects of memantine in a clinical case ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04966546

NCT04966546 | Targeting Spreading Depolarization After ... Compare clinical outcomes between patients with SD and without 1.3. Obtain preliminary data on safety and efficacy of Memantine in subjects with SD 1.4.

3. withpower.com withpower.com/trial/early-phase-1-hematoma-subdural-10-2021-dcaa9

Memantine Hydrochloride for Subdural Hematoma This trial is testing a medication called Memantine to help elderly patients recover better after brain surgery. The goal is to improve recovery and reduce ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34657268/

Memantine Improves Recovery After Spreading ... The present study tested the hypothesis that memantine improves recovery of brain slices after SD and explored the effects of memantine in a clinical case ...

5. valueinhealthjournal.com valueinhealthjournal.com/article/S1098-3015(22)00400-4/pdf

CO103 Length of Stay, Cost, and Outcomes ... gather the safety and efficacy data of memantine therapy in prevention of neurocognitive dysfunction induced by radiation therapy in brain metastases patients.

6. valueinhealthjournal.com valueinhealthjournal.com/article/S1098-3015(22)00401-6/pdf

CO104 Efficacy of Memantine in Preventing ... The data indicate that tamoxifen may not be an effective choice of therapy in neoadjuvant setting, wherein letrozole has a marked effectiveness in preoperative.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2762361/

Memantine: a review of studies into its safety and efficacy in ... Patients receiving memantine had statistically significantly better outcomes, with mild adverse effects. Post-hoc analysis revealed that the subgroup of VaD, ...