Effect of Melatonin on Seizure Outcome, Neuronal Damage and Quality of Life in Patients With Generalized Seizure
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03590197|
Recruitment Status : Recruiting
First Posted : July 18, 2018
Last Update Posted : October 1, 2019
|Condition or disease||Intervention/treatment||Phase|
|Generalized Seizure||Drug: Melatonin 3 mg Other: Placebo||Phase 4|
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 (Clinical Trial)|
|Estimated Enrollment :||120 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Triple (Participant, Care Provider, Investigator)|
|Masking Description:||The recruited patients will be randomized by simple randomization into two treatment groups using computer-generated random codes. The random allocation code of the participants will be generated by PI who will not be involved in the patient recruitment. The codes will be assigned to a sequence of numbers and the numbered stickers will be pasted on the similar looking drug containers. The drug containers will be given to another investigator who will be responsible for patient recruitment. This process ensured allocation concealment.|
|Official Title:||Effect of Melatonin on Seizure Outcome, Neuronal Damage and Quality of Life in Patients With Generalized Seizure: A Randomized, add-on Placebo-controlled Clinical Trial|
|Actual Study Start Date :||August 6, 2018|
|Estimated Primary Completion Date :||December 31, 2019|
|Estimated Study Completion Date :||March 30, 2020|
Placebo Comparator: Control Arm
The patients in Control Arm will receive placebo with valproate (20 mg/kg).
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
- 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.
- 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)
- 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
- 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
- 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
- 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
- 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)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03590197
|Contact: Rituparna Maiti, M.Demail@example.com|
|Contact: Biswa R Mishra, M.Dfirstname.lastname@example.org|
|All India Institute of Medical Sciences (AIIMS)||Recruiting|
|Bhubaneswar, Odisha, India, 751019|
|Contact: RITUPARNA MAITI, MD 9438884191 email@example.com|
|Contact: BISWA R MISHRA, MD firstname.lastname@example.org|
|Study Chair:||Debasish Hota, D.M||AIIMS, Bhubaneswar|