fenfluramine and Convulsions, Grand Mal studies

Fenfluramine: A centrally active drug that apparently both blocks serotonin uptake and provokes transport-mediated serotonin release.
fenfluramine : A secondary amino compound that is 1-phenyl-propan-2-amine in which one of the meta-hydrogens is substituted by trifluoromethyl, and one of the hydrogens attached to the nitrogen is substituted by an ethyl group. It binds to the serotonin reuptake pump, causing inhbition of serotonin uptake and release of serotonin. The resulting increased levels of serotonin lead to greater serotonin receptor activation which in turn lead to enhancement of serotoninergic transmission in the centres of feeding behavior located in the hypothalamus. This suppresses the appetite for carbohydrates. Fenfluramine was used as the hydrochloride for treatment of diabetes and obesity. It was withdrawn worldwide after reports of heart valve disease and pulmonary hypertension.

Research Excerpts

Excerpt	Relevance	Reference
"Fenfluramine (FFA), an antiseizure medication (ASM) indicated for treating convulsive seizures in Dravet syndrome, was assessed in six patients (five female; 83%) with CDD whose seizures had failed 5-12 ASMs or therapies."	5.62	Effect of fenfluramine on convulsive seizures in CDKL5 deficiency disorder. ( Conway, E; Devinsky, O; King, L; Price, D; Schwartz, D, 2021)
"Fenfluramine (FFA), an antiseizure medication (ASM) indicated for treating convulsive seizures in Dravet syndrome, was assessed in six patients (five female; 83%) with CDD whose seizures had failed 5-12 ASMs or therapies."	1.62	Effect of fenfluramine on convulsive seizures in CDKL5 deficiency disorder. ( Conway, E; Devinsky, O; King, L; Price, D; Schwartz, D, 2021)

Research

Studies (1)

Authors

Clinical Trials (1)

Trial Overview

Trial Outcomes

Change From Baseline in Median Monthly Convulsive Seizure Frequency

Timeframe	Studies, this research(%)	All Research%
pre-1990	0 (0.00)	18.7374
1990's	0 (0.00)	18.2507
2000's	0 (0.00)	29.6817
2010's	0 (0.00)	24.3611
2020's	1 (100.00)	2.80

Authors	Studies
Devinsky, O	1
King, L	1
Schwartz, D	1
Conway, E	1
Price, D	1

Trial	Phase	Enrollment	Study Type	Start Date	Status
Fenfluramine in CKDL5 Deficiency Disorder (CDD)[NCT03861871]	Phase 2	7 participants (Actual)	Interventional	2019-10-29	Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Change between baseline and Week 14 in the median number of monthly convulsive seizures. (NCT03861871)
Timeframe: Baseline, Week 14

Change in Caregiver Global Impression of Change (CGIC) Score

Intervention	Number of monthly seizures (Median)
Fenfluramine Hydrochloride	88.429

The CGIC is a 1-item, parent/caregiver-completed assessment used determine how much their child/care-recipient has improved with treatment. The instrument asks parents/caregivers to rate their child's/care-recipient's improvement as: 1) very much improved; 2) much improved; 3) minimally improved; 4) unchanged; 5) a little worse; 6) much worse; 7) very much worse; the total score correspondingly ranges from 1-7. (NCT03861871)
Timeframe: Baseline, Week 14

Change in Investigator Global Impression of Change (IGIC) Score

Intervention	score on a scale (Mean)
Fenfluramine Hydrochloride	-2.429

The IGIC is a 1-item, investigator-completed assessment used determine how much a patient has improved with treatment. The instrument asks the investigator to rate patients' improvement as: 1) very much improved; 2) much improved; 3) minimally improved; 4) unchanged; 5) a little worse; 6) much worse; 7) very much worse; the total score correspondingly ranges from 1-7. (NCT03861871)
Timeframe: Baseline, Week 14

Change in Pediatric Quality Of Life (PEDS-QL) Epilepsy Module Raw Score

Intervention	score on a scale (Mean)
Fenfluramine Hydrochloride	1.571

The PedsQL Epilepsy Module is a 29-item measure with five scales: Impact, Cognitive, Sleep, Executive Function, and Mood/Behavior. The Impact scale (nine items) assesses how epilepsy interferes with daily activities, interacting with peers, independence, and increased disease burden due to treatment. The Cognitive Scale (six items) assesses memory, ability to learn new materials, school-related difficulties, and reading difficulties. The Sleep Scale (three items) assesses fatigue and sleep difficulties. The Executive Function Scale (six items) assesses organization, task initiation, impulsivity, and inattention. The Mood/Behavior Scale (five items) assesses feelings of anger, sadness, worries, and frustration tolerance. Scores range from 0-100 for each subscale, with higher scores representing better quality of life. The raw score is the sum of each subscale score and ranges from 0-500. (NCT03861871)
Timeframe: Baseline, Week 14

Change in Quality of Life in Childhood Epilepsy (QOLCE) Score

Intervention	score on a scale (Mean)
Fenfluramine Hydrochloride	-103.571

Parent/caregiver-completed assessment assessing how epilepsy affects day-to-day functioning of their child/care-recipient in various life areas. Each item is ranked on a 5-point Likert scale from 1 (response correlated with the lowest possible quality of life) to 5 (response correlated with the highest possible quality of life). Item scores are then transformed to a 0-100 scale as follows: 1 = 0, 2 = 25, 3 = 50, 4=75, and 5=100. The total score is the average of all item scores and ranges from 0-100. Higher scores indicate greater quality of life; an increase in scores indicates quality of life increased during the observational period. (NCT03861871)
Timeframe: Baseline, Week 14

fenfluramine and Convulsions, Grand Mal