Growth and Development-related Outcomes in Children With Transfusion-dependent Beta-thalassemia After Gene Therapy

Study Overview
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Brief Summary
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The investigate will conduct a cohort study to compare the growth and development, metabolism, lifestyle behavior, and health-related quality of life among three groups: children with transfusion-dependent β-thalassemia (TDT) who have received gene therapy, TDT children with lifelong supportive therapy and healthy children.

Official Title
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Growth and Development, Health-related Quality of Life of Children With Transfusion-dependent Beta-thalassemia After Gene Therapy

Conditions
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Transfusion-dependent Beta-Thalassemia, Gene Therapy

Intervention / Treatment
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* Genetic: Gene therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Gene therapy group-inclusion Male or female age of 3-14 years TDT Children who have received gene therapy. Subjects who are willing and able to provide written informed consent. Supportive therapy group-inclusion Gender same as the matched case Age similar to the matched case Children with β-TDT No history of gene therapy or allogeneic hematopoietic stem cell transplantation Subjects who are willing and able to provide written informed consent. Healthy children group-inclusion Gender same as the matched case Age similar to the matched case Subjects who are willing and able to provide written informed consent. Exclusion Criteria: Diagnosis of compound α-thalassemia Uncontrolled systemic fungal, bacterial, or viral infection History of malignant solid tumors, myeloproliferative or immunodeficiency diseases Diagnosed with mental illness Patients considered to be ineligible for the study by the investigator for reasons other than the above Discontinuation of Study : Subjects who are unwilling or unable to continue participating in the study (withdrawal of informed consent) may withdraw from the study Subjects who received gene therapy or allogeneic hematopoietic stem cell transplantation during the study The subject is seriously non-compliant with the study requirements, such as missing 2 consecutive visits Subject lost to follow-up

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 14 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Gene therapy group<br>TDT Children who have received gene therapy between 3 14 years old. | Genetic: Gene therapy<br>* Autologous edited hematopoietic stem cell transplantation<br>|
| Supportive therapy group<br>TDT Children who received lifelong treatment with blood transfusions and iron chelation. They were selected based on the age and sex of the gene therapy group. | |
| Healthy children group<br>Healthy children were selected based on the age and sex of the gene therapy group. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Growth in pediatric subjects will be assessed by height. | Height in meters. | Up to 5 years. | 
| Growth in pediatric subjects will be assessed by weight. | Weight in kilograms. | Up to 5 years. | 
| Growth in pediatric subjects will be assessed by the head and chest circumference. | Head and chest circumference in centimeters. | Up to 5 years. | 
| Growth in pediatric subjects will be assessed by interocular distance. | Interocular distance in centimeters. | Up to 5 years. | 
| Growth in pediatric subjects will be assessed by bone density. | Bone density measurement is measured by a procedure called densitometry, performed in the radiology medicine departments of hospitals or clinics. The result is the bone mineral density in grams per unit area (g/cm2). | Up to 5 years. | 
| The pubertal status will be measured using by Tanner scale. | The Tanner scale, a well-known technique used to define pubertal stage, is based on physical measurements of development based on external primary and secondary sex characteristics (from Tanner 1: pre-pubertal to Tanner 5: mature adolescent).It was developed by Marshall and Tanner while conducting a longitudinal study during the 1940s to the 1960s in England. Based on observational data, they developed separate scales for the development of external genitalia: phallus, scrotum, and testes volume in males; breasts in females; and pubic hair in both males and females. | Up to 5 years. | 
| Hormonal levels will be measured by clinical examination. | Hormonal levels included thyroid-stimulating hormone (TSH), serum triiodothyronine (T3), serum-free triiodothyronine (T4), growth hormone (GH, including IGF-1 and IGF-2), and sex hormone examination. Sex hormone examination is only for the following subjects: estradiol, FSH and LH for girls aged 9-18; testosterone, FSH and LH for boys aged 12-18. | Up to 5 years. | 
| Quality of life will be measured using by Pediatric Quality of Life Inventory (PedsQL) at baseline and the end of the study. | The Pediatric Quality of Life Inventory (PedsQL) is a valid, standardized, generic, and self-reporting assessment tool to measure health-related quality of life HRQOL for pediatrics and adolescents. PedsQL contain 23-items, and consists of the following: physical functioning, emotional functioning, social functioning, and school functioning. Each item is scored on a 5-point scale, scores are linearly transformed to a 0-100 scale in which high score means better condition. | Up to 5 years. | 
| Lifestyle behaviors will be assessed by general questioning. |  | Up to 5 years. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Transfusion-dependent Beta-Thalassemia, gene therapy, cohort study, case-control