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Therapeutic Response Evaluation and Adherence Trial (TREAT) (TREAT)

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ClinicalTrials.gov Identifier: NCT02286154
Recruitment Status : Recruiting
First Posted : November 7, 2014
Last Update Posted : September 14, 2020
Sponsor:
Information provided by (Responsible Party):
Children's Hospital Medical Center, Cincinnati

Brief 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.

Condition or disease Intervention/treatment Phase
Anemia, Sickle Cell Drug: Hydroxyurea Not Applicable

Detailed 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Therapeutic Response Evaluation and Adherence Trial (TREAT): A Prospective Study of Hydroxyurea for Children With Sickle Cell Anemia
Study Start Date : October 2014
Estimated Primary Completion Date : October 2024
Estimated Study Completion Date : October 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Anemia
Drug Information available for: Hydroxyurea

Arm Intervention/treatment
Experimental: Hydroxyurea
All enrolled participants will receive hydroxyurea, but upon enrollment, participants will be identified as part of the "New Cohort" or "Old Cohort" "New Cohort" participants include those who are not receiving hydroxyurea therapy upon study entry. "Old Cohort" participants include those who are already receiving hydroxyurea therapy upon study entry. New Cohort participants will have starting dose predicted using PK/PD data and Old Cohort participants will continue dosing per clinical guidelines.
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.




Primary Outcome Measures :
  1. Time to Reach Maximum Tolerated Dose (months) [ Time Frame: Twelve months ]
    Time it takes to reach maximum tolerated dose (MTD) of hydroxyurea quantified in months.


Secondary Outcome Measures :
  1. Hydroxyurea adherence [ Time Frame: Monthly until MTD then yearly up to ten years ]
    Hydroxyurea adherence as measured by analysis of urine metabolites

  2. Neurological function [ Time Frame: Yearly ]
    Neurological function as measured by transcranial Doppler study (yearly), brain MRI (every 5 years beginning at age 5).

  3. Non-invasive Transcranial Cerebral Oximetry [ Time Frame: Monthly until MTD then every six months, up to ten years ]
    Non-invasive transcranial cerebral oximetry

  4. Splenic function [ Time Frame: Annually up to ten years ]
    Splenic function as measured by pocked red blood cell counts ("pit counts")

  5. Kidney function [ Time Frame: Annually, up to ten years ]
    Kidney function as measured by BUN/creatinine, urinalysis, and cystatin-C

  6. Cardiac function (assessment and growth) [ Time Frame: Every Five Years, up to 21 years of age ]
    Cardiac function as measured by echocardiogram and ECG

  7. Assessment of Growth [ Time Frame: Every six months, up to ten years ]
    Assessment of growth as defined by height and weight



Information from the National Library of Medicine

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Ages Eligible for Study:   6 Months to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Diagnosis of sickle cell anemia (HbSS or Hbβ0-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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02286154


Contacts
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Contact: Amanda Pfeiffer, LPC, CCRP 513-803-4977 amanda.pfeiffer@cchmc.org
Contact: Adriane Hausfeld, RN,BSN,CCRP (513)803-3236 adriane.hausfeld@cchmc.org

Locations
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United States, Ohio
Cincinnati Children's Hospital Medical Center Recruiting
Cincinnati, Ohio, United States, 45229
Contact: Patrick McGann, MD, MS    513-803-4991    patrick.mcgann@cchmc.org   
Contact: Amanda Pfeiffer, LPC, CCRP    (513)803-4977    amanda.pfeiffer@cchmc.org   
Sponsors and Collaborators
Children's Hospital Medical Center, Cincinnati
Investigators
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Principal Investigator: Patrick McGann, MD, MS Children's Hospital Medical Center, Cincinnati
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Children's Hospital Medical Center, Cincinnati
ClinicalTrials.gov Identifier: NCT02286154    
Other Study ID Numbers: CCHMC_TREAT
First Posted: November 7, 2014    Key Record Dates
Last Update Posted: September 14, 2020
Last Verified: September 2020
Keywords provided by Children's Hospital Medical Center, Cincinnati:
Hydroxyurea
Sickle Cell
Pharmacokinetics
dynamics
genomics
Additional relevant MeSH terms:
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Anemia
Anemia, Sickle Cell
Hematologic Diseases
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Hemoglobinopathies
Genetic Diseases, Inborn
Hydroxyurea
Antineoplastic Agents
Antisickling Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors