A Study of the Impact of Hemophilia and Its Treatment on Brain Development, Thinking and Behaviour in Children With Hemophilia (eTHINK)

• ClinicalTrials.gov Identifier: NCT03660774
• Recruitment Status: Completed
• First Posted: September 7, 2018
• Last Update Posted: November 22, 2019
• Sponsor: Novo Nordisk A/S
• Information provided by (Responsible Party): Novo Nordisk A/S

Study Description

Brief Summary:

The Hemophilia Growth and Development Study (HGDS) nearly 25 years ago showed haemophilia and HIV impacted brain development, thinking, and behaviour in children and adolescents. The eTHINK study is designed to understand whether advances in hemophilia treatment have removed any impact of hemophilia. If there still is an impact of hemophilia, the eTHINK study will help to identify which children or adolescents are still at risk, and how to screen other children. Participants and their child will participate in a comprehensive assessment of child's brain development, thinking and behavior through completing tests and questionnaires. There is only one study visit of 1 to 1.5 hours with no follow-up required

Condition or disease	Intervention/treatment
Haemophilia A; Haemophilia B	Other: No treatment given

Study Design

• Study Type: Observational
• Actual Enrollment: 563 participants
• Observational Model: Ecologic or Community
• Time Perspective: Cross-Sectional
• Official Title: Evolving Treatment of Hemophilia's Impact on Neurodevelopment, Intelligence and Other Cognitive Functions (eTHINK)
• Actual Study Start Date: September 27, 2018
• Actual Primary Completion Date: October 11, 2019
• Actual Study Completion Date: October 11, 2019

Groups and Cohorts

Group/Cohort

Intervention/treatment

Patients with hemophilia; Children and young adults with hemophilia A or B, all severities, treated in the hemophilia treatment center (comprehensive care) setting, including participation of caregivers/parents completing questionnaires designed to evaluate neurologic, neurocognitive and neurobehavioral function and development.

Other: No treatment given; The participants will undergo a brief physical examination focused on neurologic function (muscle function, sensation, coordination, walking). Parents will be asked by the study team or the psychologist about their children and will complete several commonly used standard surveys about brain development, thinking, behavior, and decision making. The participants will also engage with the psychologist to evaluate development or thinking (IQ), and depending on their age they may be asked to complete one or more commonly used standard surveys about behavior and decision making.

Outcome Measures

Primary Outcome Measures :

1. Cognition composite score according to the BAYLEY-III instrument [ Time Frame: Day 1 ]
   Normalized score compared to US population (0 = equivalent to US average, negative = below US average, positive = above US average
2. Behavioural Symptoms Index according to Behavior Assessment System for Children - Third Edition (BASC-3) parent rating scale [ Time Frame: Day 1 ]
   Normalized score compared to US population (0 = equivalent to US average, negative = below US average, positive = above US average
3. Adaptive behaviour domain score according to Adaptive Behavior Assessment System, Third Edition (ABAS-3) rating scale [ Time Frame: Day 1 ]
   Normalized score compared to US population (0 = equivalent to US average, negative = below US average, positive = above US average
4. Global executive composite index according to Behavior Rating Inventory of Executive Function (BRIEF) [ Time Frame: Day 1 ]
   Normalized score compared to US population (0 = equivalent to US average, negative = below US average, positive = above US average
5. Attention and processing speed (full scale IQ) according to Wechsler Preschool and Primary Scale of Intelligence-4th Edition (WPPSI-IV) for age group 4-6 years or Wechsler Abbreviated Scale of Intelligence, 2nd Edition (WASI-II) for age group 7-22 years [ Time Frame: Day 1 ]
   Normalized score compared to US population (0 = equivalent to US average, negative = below US average, positive = above US average

Eligibility Criteria

• Ages Eligible for Study: 1 Year to 21 Years (Child, Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

Children and young adults with hemophilia A or B, all severities

Criteria

Inclusion Criteria: - Male child or young adult (ages 1:0-3:6 and 4:0-21:11 years with diagnosis of congenital hemophilia A or B, any severity, with or without inhibitors - Parent able and willing to provide consent, and young adult with hemophilia (age 18-21) able to provide consent; children (ages 7-14) and adolescents/young adults (ages 14-17) able and willing to provide assent based upon local institutional policies - Parent able and willing to complete neurodevelopment and cognitive parent reported scales during comprehensive or other Hemophilia Treatment Center visit for about 45-60 minutes in English or Spanish depending on age group) - Children, adolescents and young adults with hemophilia (ages 1-21) able to participate in assessments of development and intelligence for about 40-45 minutes and adolescents and young adults (age 11-21) with hemophilia able and willing to complete additional self-assessment scales for about 30-45 minutes during comprehensive or other elective visit for in English or Spanish (depending on age group) - Provision of informed consent before the start of any study-related activities Exclusion Criteria: - Patient aged 3:7-3:11 years (43-47 months) - Prior participation in the study - Prior neurocognitive screening with the same or related instruments in the prior 6 months - Patients with hemophilia or their caregivers for whom test measures may be culturally inappropriate - Patients with hemophilia with known history of alcohol or substance abuse - Patients with hemophilia who have used opiates in the past 24 hours or other illicit drugs within the past 48 hours - Patients with hemophilia currently experiencing an acute bleed that has not resolved - Patients with hemophilia with recent head injury or concussion within the past 4 weeks - Concurrent diagnosis of another bleeding or thrombotic disorder - Mental incapacity, unwillingness or language barriers precluding adequate understanding or cooperation

Contacts and Locations

Locations

United States, California

Novo Nordisk Investigational Site

Los Angeles, California, United States, 90027

Novo Nordisk Investigational Site

Orange, California, United States, 92868

Novo Nordisk Investigational Site

San Diego, California, United States, 92123

United States, Colorado

Novo Nordisk Investigational Site

Aurora, Colorado, United States, 80045

United States, District of Columbia

Novo Nordisk Investigational Site

Washington, District of Columbia, United States, 20010-2978

United States, Florida

Novo Nordisk Investigational Site

Tampa, Florida, United States, 33607

United States, Georgia

Novo Nordisk Investigational Site

Atlanta, Georgia, United States, 30322

United States, Illinois

Novo Nordisk Investigational Site

Chicago, Illinois, United States, 60612

United States, Indiana

Novo Nordisk Investigational Site

Indianapolis, Indiana, United States, 46260

United States, Louisiana

Novo Nordisk Investigational Site

New Orleans, Louisiana, United States, 70112

United States, Massachusetts

Novo Nordisk Investigational Site

Boston, Massachusetts, United States, 02215

United States, Michigan

Novo Nordisk Investigational Site

Ann Arbor, Michigan, United States, 48105

Novo Nordisk Investigational Site

Detroit, Michigan, United States, 48201

United States, Minnesota

Novo Nordisk Investigational Site

Minneapolis, Minnesota, United States, 55404

United States, Nebraska

Novo Nordisk Investigational Site

Omaha, Nebraska, United States, 68198-6828

United States, North Carolina

Novo Nordisk Investigational Site

Charlotte, North Carolina, United States, 28204

United States, Ohio

Novo Nordisk Investigational Site

Cleveland, Ohio, United States, 44106

United States, Oklahoma

Novo Nordisk Investigational Site

Oklahoma City, Oklahoma, United States, 73104

United States, Pennsylvania

Novo Nordisk Investigational Site

Philadelphia, Pennsylvania, United States, 19134

United States, Tennessee

Novo Nordisk Investigational Site

Nashville, Tennessee, United States, 37212

United States, Utah

Novo Nordisk Investigational Site

Salt Lake City, Utah, United States, 84113

United States, Washington

Novo Nordisk Investigational Site

Seattle, Washington, United States, 98105

Sponsors and Collaborators

Novo Nordisk A/S

Investigators

• Study Director: Clinical Reporting Anchor and Disclosure (1452); Novo Nordisk A/S

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Buranahirun C, Walsh KS, Mrakotsky C, Croteau SE, Rajpurkar M, Kearney S, Hannemann C, Wilkening GN, Shapiro KA, Cooper DL. Neuropsychological function in children with hemophilia: A review of the Hemophilia Growth and Development Study and introduction of the current eTHINK study. Pediatr Blood Cancer. 2020 Jan;67(1):e28004. doi: 10.1002/pbc.28004. Epub 2019 Oct 8.

• Responsible Party: Novo Nordisk A/S
• ClinicalTrials.gov Identifier: NCT03660774
• Other Study ID Numbers: HAEM-4436; U1111-1202-3415 ( Other Identifier: World Health Organization (WHO) )
• First Posted: September 7, 2018
• Last Update Posted: November 22, 2019
• Last Verified: November 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com
• URL: http://novonordisk-trials.com

• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Hemophilia A; Hemophilia B; Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Genetic Diseases, X-Linked