Effect of Melatonin on Seizure Outcome, Neuronal Damage and Quality of Life in Patients With Generalized Epilepsy

September 1, 2020 updated by: RITUPARNA MAITI, All India Institute of Medical Sciences, Bhubaneswar

Effect of Melatonin on Seizure Outcome, Neuronal Damage and Quality of Life in Patients With Generalized Epilepsy: A Randomized, add-on Placebo-controlled Clinical Trial

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

104

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • India
    • Odisha
      • Bhubaneswar, Odisha, India, 751019
        • All India Institute of Medical Sciences (AIIMS)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 60 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • All patients with the clinical diagnosis of generalized epilepsy with generalised onset motor seizure (ILAE 2017) with a history of an episode of seizure within 72 hours of presentation.
  • Patients aged 18-60 years, of either sex.
  • Treatment-naive patients or patients who had not taken any treatment for at least 4 weeks before inclusion.

Exclusion Criteria:

  • History of any recent traumatic brain injury, cerebral ischemia/TIA/stroke.
  • Patients with neuroendocrinal tumors.
  • History of any invasive neurosurgical/non-invasive neuropsychiatric procedure.
  • Patients who are already under treatment for the presenting conditions.
  • Medication history of psychoactive or central nervous system depressant drugs.
  • Pregnant and nursing women.
  • Patients with a history of allergy to valproate, melatonin or other melatonin agonists.
  • Patients with drug/alcohol abuse.
  • Patients with any hepatic dysfunction.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Control Arm
The patients in Control Arm will receive placebo with valproate (20 mg/kg).
Other: Placebo
Placebo with Valproate
Experimental: Melatonin Arm
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Responder Rate from baseline
Time Frame: Baseline, 8 weeks
Responder rate is defined as percentage of patients having ≥50% reduction in seizure frequency.
Baseline, 8 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in seizure severity from baseline
Time Frame: Baseline , 8 weeks
The change in seizure severity in terms of change in Chalfont-National Hospital seizure severity scale (NHS3)
Baseline , 8 weeks
Change in neuronal damage from baseline
Time Frame: Baseline, 8 weeks
The change in neuronal damage in terms of change in serum NSE (Neuron-specific Enolase) level
Baseline, 8 weeks
Change in sleep quality from the baseline
Time Frame: Baseline, 8 weeks
The change in sleep quality in terms of change in Pittsburgh sleep quality index (PSQI) score
Baseline, 8 weeks
Change in day time sleepiness from the baseline
Time Frame: Baseline, 8 weeks
The change in daytime sleepiness in terms of change in Epworth sleepiness scale
Baseline, 8 weeks
Change in antioxidant property from the baseline
Time Frame: Baseline, 8 weeks
The change in antioxidant property in terms of change in serum glutathione reductase
Baseline, 8 weeks
Change in the quality of life from the baseline
Time Frame: Baseline, 8 weeks
The change in the quality of life in terms of change in Quality of Life in Epilepsy Inventory (QOLIE-31)
Baseline, 8 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

All India Institute of Medical Sciences, Bhubaneswar

Investigators

  • Study Chair: Debasish Hota, D.M, AIIMS, Bhubaneswar

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 6, 2018

Primary Completion (Actual)

March 3, 2020

Study Completion (Actual)

April 12, 2020

Study Registration Dates

First Submitted

July 6, 2018

First Submitted That Met QC Criteria

July 6, 2018

First Posted (Actual)

July 18, 2018

Study Record Updates

Last Update Posted (Actual)

September 3, 2020

Last Update Submitted That Met QC Criteria

September 1, 2020

Last Verified

September 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IEC/AIIMSBBSR/PGTh/18-19/02

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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