Prevention of West Syndrome With Low-dose Adrenocorticotropin Hormone (ACTH) (PREVENT-WS)

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Ann & Robert H Lurie Children's Hospital of Chicago
Sponsor:
Collaborator:
Thrasher Research Fund
Information provided by (Responsible Party):
John J Millichap, MD, Ann & Robert H Lurie Children's Hospital of Chicago
ClinicalTrials.gov Identifier:
NCT01367964
First received: June 3, 2011
Last updated: July 30, 2014
Last verified: July 2014
  Purpose

West syndrome (WS) is a specific type of epilepsy (or seizure disorder) that has three features: infantile spasms (type of seizure), loss of milestones, and a specific pattern on electroencephalogram (EEG or brain wave test) called hypsarhythmia. The purpose of this study is to detect pre-hypsarhythmia in infants at high-risk for WS and determine whether treatment with ACTH will prevent WS.


Condition Intervention
West Syndrome
Drug: adrenocorticotropin hormone

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Early Treatment of Infants at High Risk of Developing West Syndrome With Low-dose Adrenocorticotropin Hormone (ACTH)

Resource links provided by NLM:


Further study details as provided by Ann & Robert H Lurie Children's Hospital of Chicago:

Primary Outcome Measures:
  • Evidence for improvement in the EEG one month following initiation of the 2 week course of low-dose ACTH. [ Time Frame: 1 month ] [ Designated as safety issue: No ]
    Eligible infants with an abnormal EEG at 3 months will be screened for pre-hypsarhythmia by serial EEGs at 4, 5, 6, 9 & 12 months. Each EEG is assigned a type (0-4). If pre-hypsarhythmia (Type 3) is detected, ACTH treatment is given for 2 weeks and an EEG is performed one month later. Primary outcome is improvement in EEG (as defined by assigned type).


Secondary Outcome Measures:
  • Diagnosis of West syndrome during the study period. [ Time Frame: 3 months to 12 month corrected age. ] [ Designated as safety issue: No ]
    Subjects, whether treated with ACTH or not, will be followed clinically and with serial EEG to assess for West syndrome (infantile spasms, hypsarhythmia, and developmental regression).


Estimated Enrollment: 28
Study Start Date: July 2011
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ACTH treatment
Enrolled infants with an abnormal EEG at 3 months old will have serial EEGs (each assigned a type) to identify pre-hypsarhythmia (Type 3). Infants who develop pre-hypsarhythmia at any time during the study period (3 months to 12 months old) will be offered treatment with adrenocorticotropin hormone.
Drug: adrenocorticotropin hormone
ACTH 16 units intramuscular injection once daily for 2 weeks
Other Name: H.P. Acthar® Gel (repository corticotropin injection)

Detailed Description:

The long-term neurological sequelae of intractable epilepsy that begins in infancy are devastating. A true anti-epileptogenic treatment trial is needed. The intervention proposed herein will succeed because it is based on solid clinical observations, uses a medication that is clearly effective in practice, and it relies on a highly reliable time-tested surrogate marker of epilepsy: the EEG. The study is focused on a very specific condition, West syndrome (WS), defined by infantile spasms, hypsarhythmia, and developmental regression. Conventional antiepileptic drugs are not only inadequate in controlling spasms, but unable to spare the developing brain from epileptogenic insults or to modify disease progression. Early recognition of spasms and prompt adrenocorticotropin hormone (ACTH) therapy offer the best option for electroclinical cessation of spasms and for favorable long term developmental outcome. Neonatal hypoxic ischemic encephalopathy (HIE) and cystic periventricular leukomalacia (PVL) have been identified as significant risk factors for WS. Focal epileptiform discharges or multifocal spikes in the EEG often precede WS and is highly predictive of future progression to hypsarhythmia. There is a paucity of well-designed adequately powered randomized controlled trials to show the efficacy of different dosages and durations of ACTH in WS. Furthermore, for 160 years since the first description of WS, not a single study has utilized a preemptive strategy to halt the evolution of epileptogenic process from perinatal brain injury to abnormal EEG followed by WS.

Hypothesis 1: A specific EEG pattern, pre-hypsarhythmia, appears 4-8 weeks prior to development of hypsarhythmia and reliably predicts development of WS in infants with HIE or PVL.

Aim 1. To identify infants at high risk for developing WS.

Hypothesis 2: Preemptive ACTH will halt the evolution of hypsarhythmia and improve the EEG patterns in infants with pre-hypsarhythmic EEG.

Aim 2. To determine whether a low dose ACTH improves EEG, we will repeat EEG one month after a 2 week course of daily ACTH.

Design: A single treatment arm exploratory study utilizing a two-stage "minimax optimal" design that yields a first stage sample size of 12 that requires 4 or more successes to proceed (and n=16 in stage 2; total n=28 over 2 years) using EEG as the surrogate biomarker for clinical response. The two-stage design exposes the smallest number of infants to treatment and provides information on adverse events and short-term clinical response with a short duration and at a low cost.

  Eligibility

Ages Eligible for Study:   3 Months to 12 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Infants with an abnormal EEG at 3 months corrected age and one or more of the following diagnoses:

    1. Periventricular leukomalacia (PVL)
    2. Neonatal intraventricular hemorrhage (IVH)
    3. Neonatal hypoxic ischemic encephalopathy (HIE)

Exclusion Criteria:

  • Infants with any of the following diagnoses:

    1. Genetic abnormality
    2. Progressive degenerative metabolic condition
    3. Other symptomatic epileptic encephalopathy (e.g. Ohtahara syndrome)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01367964

Contacts
Contact: John J. Millichap, MD 312-227-3540 jmillichap@luriechildrens.org
Contact: Sookyong Koh, MD, PhD 312-227-3540 skoh@luriechildrens.org

Locations
United States, Illinois
Ann & Robert H. Lurie Children's Hospital of Chicago Recruiting
Chicago, Illinois, United States, 60611
Contact: John J Millichap, MD    312-227-3540    jmillichap@luriechildrens.org   
Contact: Sookyong Koh, MD, PhD    312-227-3540    skoh@luriechildrens.org   
Principal Investigator: John J Millichap, MD         
Principal Investigator: Sookyong Koh, MD, PhD         
Sponsors and Collaborators
Ann & Robert H Lurie Children's Hospital of Chicago
Thrasher Research Fund
Investigators
Principal Investigator: John J. Millichap, MD Ann & Robert H. Lurie Children's Hospital of Chicago and Northwestern University Feinberg School of Medicine
Principal Investigator: Sookyong Koh, MD, PhD Ann & Robert H. Lurie Children's Hospital of Chicago and Northwestern University Feinberg School of Medicine
Principal Investigator: Doulgas R Nordli, Jr, MD Ann & Robert H. Lurie Children's Hospital of Chicago and Northwestern University Feinberg School of Medicine
Principal Investigator: Leon G Epstein, MD Ann & Robert H. Lurie Children's Hospital of Chicago and Northwestern University Feinberg School of Medicine
  More Information

Publications:
Responsible Party: John J Millichap, MD, Attending Physician, Division of Neurology, Ann & Robert H Lurie Children's Hospital of Chicago
ClinicalTrials.gov Identifier: NCT01367964     History of Changes
Other Study ID Numbers: 2011-14518
Study First Received: June 3, 2011
Last Updated: July 30, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Ann & Robert H Lurie Children's Hospital of Chicago:
Hypsarrhythmia
Spasms, Infantile
West Syndrome

Additional relevant MeSH terms:
Spasms, Infantile
Epilepsy, Generalized
Epilepsy
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Adrenocorticotropic Hormone
Hormones
Beta-Endorphin
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 19, 2014