Treatment of Sunflower Syndrome With ZX008 (Fenfluramine Hydrochloride) in Children and Young Adults (Ages 4-25).

Summary

Sunflower Syndrome (also referred to as Self-induced Photosensitive Epilepsy) is a rare epileptic disorder characterized by a distinctive seizure that manifests itself in a highly stereotyped physical behavior. Seizure types associated with Sunflower Syndrome include absence seizures and generalized tonic-clonic seizures. Individuals with Sunflower Syndrome obsessively seek out a light source, stare at the light source, and wave one hand in front of their eye(s). Electroencephalogram (EEG) features include generalized spike and wave discharges interictally, and typically strong photoparoxysmal response during photic stimulation. Currently, Sunflower syndrome is poorly characterized in medical literature and is often misunderstood at the clinical level. The name self-induced photosensitive epilepsy may be a misnomer as research concerning the neurochemical and neuropsychological pathways cannot conclusively determine that it is self-induced (conscious behavior) as the name implies. Although some reports have concluded that the hand waiving induces the seizure, these findings are not consistent throughout scientific literature. In fact, an EEG report found that the seizures can begin simultaneously with the hand waving. This suggests that the hand waving may in fact be part of the seizure, not the cause. There are no treatments specifically approved for the treatment of Sunflower Syndrome in the United States. Broad spectrum anticonvulsant medications, including sodium valproate, lamotrigine, levetiracetam, and clobazam, have not shown full efficacy in seizure prevention in patients with Sunflower Syndrome. Accordingly, there remains a significant unmet need for an approved treatment for children and adults with Sunflower Syndrome. Because this epilepsy typically does not respond to anticonvulsant medications, and because Aicardi described the successful treatment with fenfluramine of at least one child with this syndrome, the investigators of this study will investigate if fenfluramine is an effective, safe and well tolerated treatment for Sunflower Syndrome. The primary objective of this study is to determine the efficacy of ZX008 on seizure frequency in children and young adults with Sunflower Syndrome. The goal of treatment is to provide a 30 percent or greater reduction of generalized tonic-clonic seizures and/or hand waving associated with absence seizures. Secondary objectives of the study include evaluation of the effect of ZX008 (fenfluramine hydrochloride) on EEG patterns and quality of life. Patients with Sunflower Syndrome often experience low self-esteem, bullying due to the unusual motor movements associated with their seizures, school performance issues, anxiety, and depression. The study population will include pediatric and young adult patients seen by Elizabeth A. Thiele, M.D., Ph.D. at MGH's Pediatric Epilepsy Clinic who were identified as candidates. The Principal Investigator (PI) will follow up to 20 patients with Sunflower Syndrome who will be taking ZX008.

Timeline

Start

2019-05-31

Primary completion

2021-11-25

Completion

2024-07-19

Publications

• Background Aicardi J, Gastaut H. Treatment of self-induced photosensitive epilepsy with fenfluramine. N Engl J Med. 1985 Nov 28;313(22):1419. doi: 10.1056/NEJM198511283132218. No abstract available.
• Background Ames FR. "Self-induction" in photosensitive epilepsy. Brain. 1971;94(4):781-98. doi: 10.1093/brain/94.4.781. No abstract available.
• Background Ames FR, Saffer D. The sunflower syndrome. A new look at "self-induced" photosensitive epilepsy. J Neurol Sci. 1983 Apr;59(1):1-11. doi: 10.1016/0022-510x(83)90076-x.
• Background Belcastro V, Striano P. Self-induction seizures in sunflower epilepsy: a video-EEG report. Epileptic Disord. 2014 Mar;16(1):93-5. doi: 10.1684/epd.2014.0630.
• Background Boel M, Casaer P. Add-on therapy of fenfluramine in intractable self-induced epilepsy. Neuropediatrics. 1996 Aug;27(4):171-3. doi: 10.1055/s-2007-973781.
• Background Chieffo D, Battaglia D, Lettori D, Del Re M, Brogna C, Dravet C, Mercuri E, Guzzetta F. Neuropsychological development in children with Dravet syndrome. Epilepsy Res. 2011 Jun;95(1-2):86-93. doi: 10.1016/j.eplepsyres.2011.03.005. Epub 2011 Apr 6.
• Background Fuller RW, Snoddy HD, Robertson DW. Mechanisms of effects of d-fenfluramine on brain serotonin metabolism in rats: uptake inhibition versus release. Pharmacol Biochem Behav. 1988 Jul;30(3):715-21. doi: 10.1016/0091-3057(88)90089-5.
• Background LIVINGSTON S, TORRES IC. PHOTIC EPILEPSY: REPORT OF AN UNUSUAL CASE AND REVIEW OF THE LITERATURE. Clin Pediatr (Phila). 1964 May;3:304-7. doi: 10.1177/000992286400300511. No abstract available.
• Patel S, Geenen KR, Dowless D, Bruno PL, Thiele EA. Follow-up to low-dose fenfluramine for Sunflower syndrome: A non-randomized controlled trial. Dev Med Child Neurol. 2023 Jul;65(7):961-967. doi: 10.1111/dmcn.15492. Epub 2022 Dec 23.

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