Melatonin supplementation for the treatment of infantile spasms: protocol for a randomised placebo-controlled triple-blind trial

Abstract

IntroductionInfantile spasms (IS) is a type of severe epileptic encephalopathy that occurs in infancy and early childhood. IS is characterised clinically by epileptic spasms, often accompanied by sleep disorder and abnormal circadian rhythm. The endogenous circadian rhythm disorder, in turn, can make spasms worse. Melatonin has also been found to have anticonvulsant and neuroprotective properties by adjusting the circadian rhythm. However, there are lack of relevant studies on controlling IS by using melatonin. This study aims to analyse the therapeutic effect of melatonin supplementation for the treatment of IS.Methods and analysisThis is a triple-blinded (trial participant, outcome assessor and the data analyst), prospective, randomised controlled trial to be conducted in the Department of Paediatrics, The First Medical Center of Chinese PLA General Hospital, Beijing, China from November 2020. Patients (n=70) aged 3 months to 2 years with IS will be recruited in this study after receiving written consent from their parents or guardians. Patients will be randomly divided into two equal groups and treated with a combination of adrenocorticotropic hormone, magnesium sulfate and either melatonin or placebo. Clinical data from the patients in the two groups before and after the treatment will be collected and compared. The primary outcome will be assessed 2 weeks later by seizure diaries and reported as the average reduced rate of spasms frequency. Secondary outcomes include the response rate (the rate of spasms-free), electroencephalogram hypsarrhythmia assessment and the psychomotor development assessment (Denver Developmental Screening Test). Sleep quality and safety will also be assessed.Ethics and disseminationThe protocol for this study was approved by the Ethics Committee of Chinese PLA General Hospital (reference number S2020-337-01) and was reported according to the Standard Protocol Items: Recommendations for Interventional Trials statement. Findings of this research will be disseminated through national and international meetings, conferences and peer-reviewed journals.Trial registration numberChiCTR2000036208.

Safety and efficacy of melatonin supplementation as an add‐on treatment for infantile epileptic spasms syndrome: A randomized, placebo‐controlled, double‐blind trial

“…17 Detailed information on the trial procedures was available in the protocol. 18 After the 2-week treatment, a 3-day assessment was repeated, and the participants underwent a 28-day follow-up period during which certain items were assessed by telephone review. A peripheral blood sample was taken from each participant at 6:00 h on the third day of the first assessment and on the last day of the treatment and stored at −80°C until measurements were performed.…”

“…All participants were simultaneously treated with a combination of ACTH and magnesium sulfate (MgSO 4 ) for 2 weeks 17 . Detailed information on the trial procedures was available in the protocol 18 . After the 2‐week treatment, a 3‐day assessment was repeated, and the participants underwent a 28‐day follow‐up period during which certain items were assessed by telephone review.…”

“…Patient etiology was also categorized into either symptomatic (structural and genetic) or unknown etiology. The melatonin group (median [range], 9 [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] months) was dominated by unknown etiology (65.7%), while the placebo group (11 [5-22] months) was mainly symptomatic etiology (65.7%). The results of the per protocol analysis are presented in Supporting Information S3: eTable 1.…”

Melatonin regulates microglial polarization to M2 cell via RhoA/ROCK signaling pathway in epilepsy

“…It has been demonstrated that MEL played important roles in neurofunctional diseases by activating MEL receptors (MT1/2) 9 . Among the reports, MEL was widely reported in the pathogenesis and progression of epilepsy, indicating a protective role for the disease 10,11 . Besides, a clinical study found that the abnormal secretion of MEL resulted in circadian rhythm disorders and immune system dysfunctions 12 .…”

“… 9 Among the reports, MEL was widely reported in the pathogenesis and progression of epilepsy, indicating a protective role for the disease. 10 , 11 Besides, a clinical study found that the abnormal secretion of MEL resulted in circadian rhythm disorders and immune system dysfunctions. 12 Meanwhile, a mechanism study showed that MEL changed the neurotransmission functions of glutamate and aminobutyric acid to regulate the electrical activity of neurons and to reduce oxidative stress responses in the alginate‐induced epilepsy of zebrafish.…”