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

Trial Summary

What is the purpose of this trial?

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 neurological problems. Memantine has been used to treat Alzheimer's disease and other neurological disorders.

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 memantine hydrochloride safe for humans?

Memantine has been used safely in treating Alzheimer's disease and other dementias, with studies showing it is generally well-tolerated. However, there have been reports of potential side effects like bradycardia (slow heart rate) and altered mental status in specific cases. ^{1 2 3 4 5}

How does the drug memantine hydrochloride differ from other treatments for subdural hematoma?

Memantine hydrochloride is unique because it is an excitatory amino acid (EAA) antagonist that has been used for neurodegenerative diseases like Alzheimer's, but it is now being explored for subdural hematoma to prevent brain damage from reduced blood flow. Unlike standard treatments that focus on surgical removal of the hematoma, memantine targets the chemical processes in the brain to protect it from further injury. ^{2 6 7 8 9}

Eligibility Criteria

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 am between 18 and 100 years old.

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

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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, 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]

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]

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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

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

2. England pubmed.ncbi.nlm.nih.gov

Effects of memantine and MK-801 on ischemia in an experimental model of acute subdural hematoma. [2013]

3. England pubmed.ncbi.nlm.nih.gov

Life-threatening altered mental status secondary to memantine in an adolescent undergoing cranial radiotherapy for medulloblastoma. [2023]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Memantine for the treatment of Alzheimer's disease: tolerability and safety data from clinical trials. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Does memantine induce bradycardia? A study in the French PharmacoVigilance Database. [2013]

6. Scotland pubmed.ncbi.nlm.nih.gov

Memantine hydrochloride in the treatment of dementia subtypes. [2013]

7. United States pubmed.ncbi.nlm.nih.gov

Effects of hypertonic/hyperoncotic treatment and surgical evacuation after acute subdural hematoma in rats. [2013]

8. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Features of memantine action profile in cholinergic deficit and intracerebral posttraumatic hematoma (hemorrhagic stroke) models in rats]. [2019]

9. China pubmed.ncbi.nlm.nih.gov

Effectiveness and safety of generic memantine hydrochloride manufactured in China in the treatment of moderate to severe Alzheimer's disease: a multicenter, double-blind randomized controlled trial. [2021]