Valproic Acid in Treating Cyanotic Breath Holding Spells

NCT04482764 | Completed Phase 1

• 1 other identifier: BHS-VPA-SH-2017
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

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.

Conditions

Breathhold

Keywords

Breath holding spells; cyanosis; valproic acid

Outcome Measures

Primary Outcomes (1)

• frequency of spells after starting treatment with valproic acid

  The parents or legal guardians are the sources of information about the frequency of spells.

  6 months

Study Arms (1)

cyanotic breath holding spells

OTHER

drug, valproic acid: 5mg/kg/d for 6 months

Drug: Valproic Acid

Interventions

Valproic Acid DRUG

Treatment of children with frequent cyanotic breath holding spells (at least 4 spells per week) with 5 mg/kg/day for 6 months.

Also known as: sodium valproate

cyanotic breath holding spells

Eligibility Criteria

• Age: 6 Months - 5 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Children with high frequency spells (≥ 4/week) of CBHS.
• Children with parents who were wishing to provide treatment to their children.
• 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.
• Follow-up for 6 months after starting treatment with valproic acid.

You may not qualify if:

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

Sponsors & Collaborators

• Assiut University: lead

Study Sites (1)

Assiut University Hospitals, Faculty of Medicine

Asyut, 71516, Egypt

Location

Related Publications (1)

• 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.

  PMID: 32969724 DERIVED

MeSH Terms

Conditions

Cyanosis

Interventions

Valproic Acid

Condition Hierarchy (Ancestors)

Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pentanoic Acids; Valerates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids, Volatile; Fatty Acids; Lipids

Study Officials

• Sherifa A Hamed, M.D.

  Assiut University, Faculty of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Neurology

Study Record Dates

• First Submitted: October 3, 2017
• First Posted: July 23, 2020
• Study Start: January 30, 2017
• Primary Completion: January 30, 2018
• Study Completion: December 30, 2018
• Last Updated: July 23, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share

Locations

EG (1)