A Phase 4 interventional study of Melatonin 3 mg and Placebo in Generalized Epilepsy, sponsored by All India Institute of Medical Sciences, Bhubaneswar. Completed at 1 site in India. Open to participants aged 18 Years to 60 Years. Per ClinicalTrials.gov, last updated 2020-09-03.
Sponsored by All India Institute of Medical Sciences, Bhubaneswar · Phase 4, Interventional, and Treatment
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.
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.
39 studies on the registry are indexed under Epilepsy, Generalized; 4 are open to participants now.
This study's enrollment of 104 is above the median of 75 across 25 interventional studies indexed under Epilepsy, Generalized.
Browse Epilepsy, Generalized studies →All India Institute of Medical Sciences, Bhubaneswar is the lead sponsor of 59 studies on the registry; 25 are open to participants now.
Counted across the registry records on this site, refreshed daily.
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Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A “mini-stroke”: temporary stroke-like symptoms caused by reduced blood flow to part of the brain, spinal cord or eye, without signs of a new stroke on a scan.
Stroke symptoms need emergency care at once, even if they go away.
TIA (transient ischaemic attack)
A “mini-stroke”: temporary stroke-like symptoms caused by reduced blood flow to part of the brain, spinal cord or eye, without signs of a new stroke on a scan.
Stroke symptoms need emergency care at once, even if they go away.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The patients in Control Arm will receive placebo with valproate (20 mg/kg).
Other: Placebo
The Experimental Arm will receive tablet melatonin as an add-on to valproate. Melatonin will be prescribed 3 mg/day to the patients and will be advised to take 30 minutes before bedtime.
Drug: Melatonin 3 mg
Melatonin 3 mg/ day with Valproate
Placebo with Valproate
Change in Responder Rate from baseline
Responder rate is defined as percentage of patients having ≥50% reduction in seizure frequency.
Time frame: Baseline, 8 weeks
Change in seizure severity from baseline
The change in seizure severity in terms of change in Chalfont-National Hospital seizure severity scale (NHS3)
Time frame: Baseline , 8 weeks
Change in neuronal damage from baseline
The change in neuronal damage in terms of change in serum NSE (Neuron-specific Enolase) level
Time frame: Baseline, 8 weeks
Change in sleep quality from the baseline
The change in sleep quality in terms of change in Pittsburgh sleep quality index (PSQI) score
Time frame: Baseline, 8 weeks
Change in day time sleepiness from the baseline
The change in daytime sleepiness in terms of change in Epworth sleepiness scale
Time frame: Baseline, 8 weeks
Change in antioxidant property from the baseline
The change in antioxidant property in terms of change in serum glutathione reductase
Time frame: Baseline, 8 weeks
Change in the quality of life from the baseline
The change in the quality of life in terms of change in Quality of Life in Epilepsy Inventory (QOLIE-31)
Time frame: Baseline, 8 weeks
Plan to share: Undecided
Ran from Aug 2018 to primary completion in Mar 2020, 18 months.
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This study is completed, as verified in Sep 2020. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Melatonin
All India Institute of Medical Sciences, Bhubaneswar