Memantine for Epileptic Encephalopathy

Kenneth Myers, MD

Status and phase: Completed; Phase 4

Conditions: Epileptic Encephalopathy, Childhood-Onset

Treatments: Drug: Memantine Hydrochloride 10 mg

Study type: Interventional

Funder types: Other

Identifiers

NCT03779672

22838

Details and patient eligibility

About

This study will evaluate the potential benefit of memantine hydrochloride as treatment for children with epileptic encephalopathy using a double-blind placebo-controlled cross-over design.

Full description

Memantine, a drug approved for Alzheimer's dementia, exerts its therapeutic effect through its action as a low to moderate affinity non-competitive (open channel) N-methyl-D-aspartate receptor (NMDA-R) antagonist, which binds preferentially to the NMDA receptor-operated cation channels. It blocks the effects of persistently elevated levels of glutamate that may lead to neuronal dysfunction. Memantine may also have anti-inflammatory effects. Memantine has been used off-label in children and adolescents with autism spectrum disorder, to improve the cognitive impairment.

Epileptic encephalopathy, as well as other forms of epilepsy, may occur as a result of multiple etiologies, including genetic and inflammatory pathologies. Ion channels were long considered to be implicated in genetic epilepsy. Indeed one of the many possible causes of epilepsy is NMDA receptor dysfunction.

In the present study, the investigators plan to investigate the potential benefit of memantine as a treatment for epileptic encephalopathy. A double-blind placebo-controlled cross-over design will be used, with participants receiving 6 weeks of memantine and 6 weeks of placebo, with a 2-week washout period in between.

Enrollment: 30 patients

Sex: All

Ages: 6 to 18 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Written informed consent obtained

• Age 6-18 years (Weight ≥ 20 kg)

• Clinical diagnosis of epileptic encephalopathy

  • Subject with epilepsy and developmental impairment;
  • Epileptic activity itself contributes to severe cognitive and behavioural impairments
  • Patients will typically have already have trialed at least two standard therapies

• Females of childbearing age:

• Negative urinary pregnancy test at screening

• Agree to use effective contraception for the duration of the study

Exclusion criteria

• Inability of a parent or legal guardian to give informed consent for any reason.
• Known hypersensitivity to memantine hydrochloride
• Taking concomitant Amantadine, Ketamine or Dextromethorphan, Cimetidine, Ranitidine, Procainamide, Quinidine, Quinine, Hydrochlorothiazide, Anticholinergics, L-dopa, Anticoagulant,
• Any degree of renal impairment

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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30 participants in 2 patient groups, including a placebo group

Memantine Hydrochloride 10 mg Placebo

Active Comparator group

Description:

Blue colour capsules, for oral administration, containing 5 mg of active memantine or matching placebo for oral administration. Dose regimen: Memantine Hydrochloride * Week #1: 5 mg id (am), 1 caps * Week #2: 5 mg bid (am and pm), 2 caps * Weeks #3-6: 5 mg am \& 2x 5 mg pm, 3 caps Washout (Weeks #7-8) Placebo * Week #9: id (am), 1 caps * Week #10: bid (am and pm), 2 caps * Weeks #11-14: 1 caps am \& 2 caps pm, 3 caps

Treatment:

Drug: Memantine Hydrochloride 10 mg

Placebo Memantine Hydrochloride 10 mg

Placebo Comparator group

Description:

Placebo * Week #1: id (am), 1 caps * Week #2: bid (am and pm), 2 caps * Weeks #3-6: 1 caps am \& 2 caps pm, 3 caps Washout (Weeks #7-8) Memantine Hydrochloride * Week #9: 5 mg id (am), 1 caps * Week #10: 5 mg bid (am and pm), 2 caps * Weeks #11-14: 5 mg am \& 2x 5 mg pm, 3 caps

Treatment:

Drug: Memantine Hydrochloride 10 mg