Therapeutic Response Evaluation and Adherence Trial (TREAT)

Anemia, Sickle Cell Clinical Trial

— TREAT  

Official title:

Therapeutic Response Evaluation and Adherence Trial (TREAT): A Prospective Study of Hydroxyurea for Children With Sickle Cell Anemia

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02286154
• Other study ID #: CCHMC_TREAT
• Status: Recruiting
• Phase: N/A
• Start date: October 2014
• Est. completion date: October 2024

Study information

• Verified date: July 2023
• Source: Children's Hospital Medical Center, Cincinnati
• Contact: Amanda Pfeiffer, LPC, CCRP
• Phone: 513-803-4977
• Email: amanda.pfeiffer[@]cchmc.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objectives of this prospective study of hydroxyurea for children with sickle cell anemia are 1) Develop and prospectively evaluate a population pharmacokinetic/pharmacodynamics model to predict the maximum tolerated dose (MTD); 2) Identify urine biomarkers of hydroxyurea adherence using a novel metabolomics approach; 3) Identify pharmacogenomics modifiers of hydroxyurea MTD; and 4) Longitudinal monitoring of the effect of hydroxyurea upon organ function and quality of life.

Description:

There is now ample clinical evidence that hydroxyurea is a safe and effective medication for adults and children with sickle cell anemia (SCA), and most hematologists agree the short-term safety and efficacy of hydroxyurea has been proven. The National Heart, Lung, and Blood Institute have recently released evidence-based guidelines for SCA, recommending that hydroxyurea be offered to all affected children as young as nine months of age, regardless of clinical severity. Despite the overwhelming evidence demonstrating safety and efficacy, hydroxyurea remains underutilized for a variety of reasons. In this prospective study, the investigators will utilize innovative strategies designed to address and overcome some of the barriers that currently limit the use of hydroxyurea for children with SCA. The investigators will utilize novel laboratory techniques and pharmacometric modeling in order to accurately predict the most effective hydroxyurea dose referred to as the maximum tolerated dose. The investigators aim to develop a screening urine test to objectively and accurately determine adherence to hydroxyurea therapy. In addition, the study will document critical laboratory and clinical characteristics of this unique population of patients with SCA who begin hydroxyurea at a young age.

This study will follow two groups of patients. The first group, referred to as the New Cohort, will include mostly young infants who are not receiving hydroxyurea therapy upon entering the study. The starting dose of hydroxyurea for each of the participants in the New Cohort will be individually determined using the novel population PK/PD dose-prediction model. The second group of study participants, referred to as the Old Cohort, will include patients who are already receiving hydroxyurea therapy upon study entry. Both the Old and New Cohort (New Cohort) will be included in the development of a urine biomarker of adherence and will be followed throughout the study to document the effect hydroxyurea has upon organ function and quality of life. It is important to note that this is not a therapeutic drug trial. Prior to enrollment in the study, participants, along with their families and clinical providers, have decided to initiate hydroxyurea therapy for clinical indications. Except for the dose prediction model for the New Cohort, participants will be treated and monitored according to the routine clinical practice guidelines of the Cincinnati Children's Hospital Comprehensive Sickle Cell Center.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: October 2024
• Est. primary completion date: October 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Months to 21 Years

Eligibility

Inclusion Criteria:

1. Diagnosis of sickle cell anemia (HbSS or Hbß0-thalassemia)

2. Age 6 months to 21 years at the time of enrollment

3. Clinical decision by patient, family, and healthcare provider to initiate hydroxyurea therapy, including patients who are transitioning from chronic transfusions to hydroxyurea therapy

Exclusion Criteria:

1. Family unwillingness to sign informed consent or comply with study treatments

Related Conditions & MeSH terms

• Anemia
• Anemia, Sickle Cell

Intervention

Drug:
• Hydroxyurea
For New Cohort participants, PK/PD data will be used to predict the most effective maximum tolerated dose. Old Cohort participants will receive hydroxyurea escalated to MTD as per local clinical guidelines.

Locations

Country	Name	City	State
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Children's Hospital Medical Center, Cincinnati

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to Reach Maximum Tolerated Dose (months)	Time it takes to reach maximum tolerated dose (MTD) of hydroxyurea quantified in months.	Twelve months
Secondary	Hydroxyurea adherence	Hydroxyurea adherence as measured by analysis of urine metabolites	Monthly until MTD then yearly up to ten years
Secondary	Neurological function	Neurological function as measured by transcranial Doppler study (yearly), brain MRI (every 5 years beginning at age 5).	Yearly
Secondary	Non-invasive Transcranial Cerebral Oximetry	Non-invasive transcranial cerebral oximetry	Monthly until MTD then every six months, up to ten years
Secondary	Splenic function	Splenic function as measured by pocked red blood cell counts ("pit counts")	Annually up to ten years
Secondary	Kidney function	Kidney function as measured by BUN/creatinine, urinalysis, and cystatin-C	Annually, up to ten years
Secondary	Cardiac function (assessment and growth)	Cardiac function as measured by echocardiogram and ECG	Every Five Years, up to 21 years of age
Secondary	Assessment of Growth	Assessment of growth as defined by height and weight	Every six months, up to ten years