Effect of Melatonin on Seizure Outcome, Neuronal Damage and Quality of Life in Patients With Generalized Epilepsy
Condition: Generalized Epilepsy
MeSH terms: Epilepsy; Seizures; Epilepsy, Generalized
Study type: Interventional
Phase: Phase 4

Summary: 
      Epilepsy is one of the most common and frequently encountered neurological conditions that
      impose a huge burden on the healthcare systems. Despite the abundance of antiepileptic drugs
      (AEDs) available, 30% of people continue to have seizures even after long-term therapy of 6-8
      years. This group of people requires a more aggressive treatment since monotherapy, the first
      choice scheme, is not sufficient to control seizure and its complications, multiple drug
      therapy or polytherapy often results in the culmination of unwanted effects. The need for an
      add-on AEDs with a good safety profile is of utmost importance.The beneficial effects of
      melatonin on sleep, its wide safety window, and its ability to cross the blood-brain barrier
      have the potential to improve the quality of life in seizure patients. Various animal studies
      have suggested that melatonin receptors are the potential targets for anticonvulsant drug
      development. In animal studies, melatonin was found to suppress generalized seizure and
      seizure susceptibility and it also has neuroprotection and synapse modulating properties.
      Some clinical trials mostly on paediatric population also found that melatonin can improve
      the clinical outcome in epilepsy. Therefore, we have planned to conduct a randomized, add-on
      placebo-controlled clinical trial on the effect of melatonin on seizure outcome, neuronal
      damage and quality of life in adult patients with generalized seizure.
    

Detailed description: 
      Epilepsy is a chronic disabling neurologic condition which often leads to numerous adverse
      long-term neurologic complications, such as behavioural and cognitive deficits, increased
      susceptibility to recurrent seizures, and neuronal injury or death. Cognitive dysfunction,
      depression, anxiety and sleep disorders are some of the highly prevalent and most
      debilitating complications of epilepsy. Despite the abundance of antiepileptic drugs (AEDs),
      even after long-term treatment of 6-8 years, 30% of patients continue having seizures. This
      group of patients requires a more aggressive treatment, since monotherapy fails to control
      seizures, considering the fact that the number of seizures is the single most important
      predictive factor for both early and long-term remission of seizures. Nevertheless,
      polytherapy often results in a number of adverse effects. The need for better-tolerated
      add-on therapy is the need of the hour to overcome this therapeutic hurdle.

      Melatonin, an endogenous hormone, acting through MT1 and MT2 receptors exert a depressive
      effect on brain excitability and have been shown to exert an anticonvulsant activity in
      various animal models. In some clinical trials also it has been found that add-on melatonin
      therapy improves the clinical outcome. Uberoset al evaluated the sleep-wake pattern, plasma
      melatonin levels and the urinary excretion of its metabolite among children with severe
      epileptic disorders, before and after a therapeutic trial with melatonin. They found sleep
      efficiency was significantly higher and better controls of convulsive episodes were achieved
      with among patients who received melatonin. Goldberg-Stern et aland Elkhayat et al concluded
      that melatonin could be effective and safe for decreasing seizure frequency and severity in
      patients with intractable epilepsy. Gupta et al found that melatonin has the potential to
      improve quality of life in pediatric epilepsy because of its beneficial effects on sleep, its
      wide safety window, and its ability to cross the blood-brain barrier. In another study by
      Jain SV et al melatonin resulted in a statistically significant decrease in sleep onset
      latency and wakefulness after sleep onset. Guptaet al also concluded that add-on melatonin
      can be of promise in the pharmacotherapy of pediatric epilepsy and as an adjunct, can be a
      putative neuroprotector in conditions involving oxidative stress like epilepsies. Dabak et al
      and Brazil et measured melatonin in febrile seizure and temporal lobe epilepsy and found to
      be lower in epilepsy in comparison to the controls.

      Our literature review reveals that till date most of the clinical studies on the effect of
      melatonin in epilepsy have been conducted in the pediatric population and there is no
      clinical trial done on its effect on seizure outcome, neuroprotective effect, sleep and
      circadian rhythm and quality of life in adult patients with epilepsy. So the present
      randomized clinical trial has been designed to fill the knowledge gap and evaluate the effect
      of add-on melatonin on seizure severity, neuronal damage and sleep quality in adult patients
      suffering from a generalized seizure.
    

Intervention name(s): Melatonin 3 mg; Placebo
Intervention type(s): Drug; Other
Intervention description(s): Melatonin 3 mg/ day with Valproate; Placebo with Valproate
Intervention MeSH terms: Melatonin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: Melatonin; Neuron-specific Enolase; Responder rate