Clinical trial NCT04482764: Valproic Acid in Treating Cyanotic Breath Holding Spells
Official title: The Effectiveness of Valproic Acid in Treating Frequent Cyanotic Breath Holding Spells
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Breathhold
Keywords: Breath holding spells
cyanosis
valproic acid
Lead sponsor: Assiut University
Sponsor class: OTHER
First posted: 2020-07-23
Enrollment: 150
Sex: ALL
Minimum age (years): 6
Maximum age (years): 5
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Breath holding spells (BHS) are common non-epileptic paroxysmal behavioral involuntary episodes occurring in up to 5.9% of healthy children. The attacks occur in early childhood (0.5-3 years) but are self-limited by school age (4-5 years old) (90%). Classically, BHS were classified as cyanotic (blue), pallid (pale) and mixed based on the color change of the child during the spell. In general, cyanotic spells have been classically described in a toddler with excessive temper tantrums \[stubborn, easily frustration or annoyed. The mechanisms of BHS are controversial. The most suggested cause of BHS is instability of the autonomic nervous system, inhibition of respiratory effort and cyanosis in cyanotic BHS and bradycardia or a brief asystole and cerebral hypoperfusion in pallid BHS. Iron deficiency anemia (IDA) has been widely regarded as a risk factor for BHS in nearly 50% of children due to reduced brain oxygenation \[4\]. It is generally agreed that the long-term prognosis is considered good \[1\]. There is no definite therapy for BHS. In children with low frequency spells, parental reassurance are just enough; however, high frequency spells may result in anxiety to the parents or fear from sudden death of the child or development of mental subnormality. Treatment of iron has been reported to result in reduction of the frequency of spells or its stoppage. Some reported improvement of BHS with piracetam \[a nootropic drug known to increase brain oxygenation\]. We did not find systematized published reports evaluating the effectiveness of antiepileptic drugs (AEDs) in reduction of spells frequency of cyanotic BHS or their stoppage.


Eligibility criteria: Inclusion criteria :

1. Children with high frequency spells (≥ 4/week) of CBHS.
2. Children with parents who were wishing to provide treatment to their children.
3. Failure of alternatives modalities of treatment (e.g. iron supplements, piracetam, non-specific vitamins, etc) (tried for ≥ 3 months) to reduce the frequency of spells or stop them.
4. Follow-up for 6 months after starting treatment with valproic acid.

Exclusion criteria:

1. Primary neurologic disease, history of epilepsy or febrile convulsions, abnormal neurological examination and abnormal EEG.
2. Primary cardiac disease or presence of long QT syndrome in the ECG.
3. Presence of a hematologic (other than IDA) or other medical disease, electrolyte disturbance, hypoglycemia, hypocalcemia, impaired kidney or liver function tests.
4. Those with a doubtful diagnosis.

Primary outcomes:
measure: frequency of spells after starting treatment with valproic acid
timeFrame: 6 months
Secondary outcomes:
Other outcomes:
Locations:
city: Assiut
country: Egypt
facility: Assiut University Hospitals, Faculty of Medicine
Study officials:
affiliation: Assiut University, Faculty of Medicine
name: Sherifa A Hamed, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hamed SA, Elhadad AF, Farghaly HS. Evaluation of the effectiveness of valproic acid for treating cyanotic breath holding spells: A Pilot prospective study. Expert Rev Clin Pharmacol. 2020 Nov;13(11):1263-1270. doi: 10.1080/17512433.2020.1828059. Epub 2020 Nov 1.