Improving Infant Hydrocephalus Outcomes in Uganda

Improving Infant Hydrocephalus Outcomes in Uganda: Predicting Developmental Outcomes and Identifying Patients at Risk for Early Treatment Failure After ETV/CPC

Neonatal postinfectious hydrocephalus (PIH) is a major public health problem in East Africa.The standard treatment has long been placement of a ventriculoperitoneal shunt (VPS) but these devices require life-long maintenance and nearly all fail multiple times. Endoscopic Third Ventriculostomy (ETV) with Choroid Plexus Cauterization (ETV/CPC) is an alternate treatment to give patients a shunt-free life. In this study, the investigators aim to optimize the metrics of evaluation as quantitative prognostic indicators of treatment response and long term outcomes.

Study Overview

• Status: Recruiting
• Conditions: Hydrocephalus
• Intervention / Treatment: Procedure: ETV/CPC

• Study Type: Observational
• Enrollment (Estimated): 400

Contacts and Locations

• Study Contact: Name: Pei-Yi Lin, PhD; Phone Number: 6179191308; Email: Ivy.Lin@childrens.harvard.edu
• Study Contact Backup: Name: Matthew Foster; Phone Number: 6179192729; Email: osp@childrens.harvard.edu

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada
      • Active, not recruiting
      • The Hospital for Sick Children
• Uganda
  • Mbale, Uganda
    • Recruiting
    • Cure Children's Hospital of Uganda
    • Contact: Edith Mbabazi, MD; Email: edith.mbabazi@cureinternational.org
    • Principal Investigator: Edith Mbabazi, MD
• United States
  • Pennsylvania
    • University Park, Pennsylvania, United States, 16802
      • Active, not recruiting
      • Penn State University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 day to 5 months (Child)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Infants less than six months old with progressive hydrocephalus

Description

Inclusion Criteria:

• Infants less than 180 days (six months) old
• Symptomatic hydrocephalus characterized by abnormal rate of head growth, full anterior fontanel, ventriculomegaly
• A parent or a guardian qualified by Ugandan law to give informed consent
• Patients from Eastern, Central and Northern districts of Uganda, and in geographic proximity to CURE hospital will be eligible

Exclusion Criteria:

• Age greater than six months
• No evidence of progressive hydrocephalus
• Patients outside of the districts specified in the inclusion criteria

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Hydrocephalus group; Inclusion criteria: Age less than six months; Symptomatic hydrocephalus characterized by abnormal rate of head growth, full anterior fontanel, ventriculomegaly; A parent or a guardian qualified by Ugandan law to give informed consent; Patients from Eastern, Central and Northern districts of Uganda, and in geographic proximity to CURE hospital will be eligible Exclusion criteria: Age greater than six months; No evidence of progressive hydrocephalus; Patients outside of the districts specified in the inclusion criteria	Procedure: ETV/CPC; The Endoscopic Third Ventriculostomy/Choroid Plexus Cauterization (ETV/CPC) will comprise a standard frontal approach with flexible endoscopy.
Control group; Inclusion criteria: Born at GA ≥ 37 weeks; Age less than six months at the time of enrollment; No known medical conditions; With a parent or a guardian qualified by Ugandan law to give informed consent; Parents live in one of the villages in the Mbale or Budaka District, in geographic proximity to CCHU. Exclusion criteria: Born at GA < 37 weeks; Age greater than six months; Evidence of one or more medical conditions; Living outside of the districts specified in the inclusion criteria.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bayley Scales of Infant Development, Third Edition (BSID-3), cognitive scaled score	Scores on the BSID-3, which is used to evaluate infants and toddlers 1 to 42 months of age, range from 1 to 19, with higher scores indicating better performance; the mean (±standard deviation(SD)) score in the general population is 10±3.	24 months of age
Incidence of ETV/CPC treatment failure	Treatment failure or success will be determined with the use of clinical and radiographic criteria.; Treatment success will be determined as the shift in the growth of head circumference to a normal rate, as plotted on a standard growth chart; decompression of the anterior fontanel; relief of symptoms of elevated intracranial pressure, such as irritability and vomiting; resolution of down-gaze or sixth cranial nerve palsy; and a decrease or arrest in ventriculomegaly as determined on Computerized Tomography (CT).; Treatment failure will be defined as treatment-related death or the need for a second operation for infection or for the recurrence of hydrocephalus.	6 months post-treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cerebral oxygen metabolism	cerebral oxygen metabolism will be measured with near-infrared spectroscopy	pre- and post-, 6, 12 months post-treatment and 24 months of age
brain volume	brain volume will be quantitatively estimated from the head CT scan	pre-, 6, 12 months post-treatment and 24 months of age
Bayley Scales of Infant Development, Third Edition (BSID-3), cognitive scaled score at 12 months post-treatment	Scores on the BSID-3, which is used to evaluate infants and toddlers 1 to 42 months of age, range from 1 to 19, with higher scores indicating better performance; the mean (±standard deviation) score in the general population is 10±3.	12 months post-treatment

Collaborators and Investigators

• Sponsor: Boston Children's Hospital
• Collaborators: The Hospital for Sick Children; Yale University; CURE Children's Hospital, Uganda
• Investigators: Principal Investigator: Pei-Yi Lin, PhD, Boston Children's Hospital

Publications and helpful links

General Publications

• Vadset TA, Rajaram A, Hsiao CH, Kemigisha Katungi M, Magombe J, Seruwu M, Kaaya Nsubuga B, Vyas R, Tatz J, Playter K, Nalule E, Natukwatsa D, Wabukoma M, Neri Perez LE, Mulondo R, Queally JT, Fenster A, Kulkarni AV, Schiff SJ, Grant PE, Mbabazi Kabachelor E, Warf BC, Sutin JDB, Lin PY. Improving Infant Hydrocephalus Outcomes in Uganda: A Longitudinal Prospective Study Protocol for Predicting Developmental Outcomes and Identifying Patients at Risk for Early Treatment Failure after ETV/CPC. Metabolites. 2022 Jan 14;12(1):78. doi: 10.3390/metabo12010078.

Study record dates

Study Major Dates

• Study Start (Actual): May 5, 2021
• Primary Completion (Estimated): January 1, 2025
• Study Completion (Estimated): January 1, 2026

Study Registration Dates

• First Submitted: August 23, 2018
• First Submitted That Met QC Criteria: August 24, 2018
• First Posted (Actual): August 28, 2018

Study Record Updates

• Last Update Posted (Actual): August 14, 2023
• Last Update Submitted That Met QC Criteria: August 9, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Hydrocephalus
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hydrocephalus
• Other Study ID Numbers: P00029806

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data will not be shared with researchers outside of the study team.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No