Evaluating People With Thalassemia: The Thalassemia Longitudinal Cohort (TLC) Study

• ClinicalTrials.gov Identifier: NCT00661804
• Recruitment Status: Completed
• First Posted: April 18, 2008
• Last Update Posted: November 11, 2011
• Sponsor: HealthCore-NERI
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); Thalassemia Clinical Research Network
• Information provided by: HealthCore-NERI

Study Description

Brief Summary:

Thalassemias are inherited blood disorders that can cause anemia and other health problems. The goal of this study is to collect information on complications of the disease among people who currently have or previously had thalassemia.

Condition or disease
Thalassemia

Detailed Description:

Thalassemias are inherited blood disorders that are characterized by low levels of hemoglobin and healthy red blood cells. The two major types of thalassemia are alpha thalassemia and beta thalassemia, and there are several forms of each type. Symptoms can range from mild to severe and may include anemia, delayed growth, bone problems, and an enlarged spleen. People with mild forms of the disease may not need any treatment, while people with moderate to severe thalassemia may be treated with blood transfusions to refresh the healthy red blood cell supply, iron chelation therapy to remove excess iron from the body, and folic acid supplements to help build healthy red blood cells. Stem cell transplants can cure the disease, but they are not widely used because of the difficulty of finding donors. This study will establish a database of people with thalassemia and people who used to have thalassemia to examine the prevalence and incidence of complications related to the disease. Participants' DNA will be analyzed and plasma will be collected for use in future studies. Participants in this study may also be asked if they are interested in enrolling in other Thalassemia Clinical Research Network studies.

This study has enrolled people with thalassemia or people whose thalassemia was cured after undergoing a stem cell transplant. At a baseline study visit, participants with thalassemia will undergo a medical history interview; a medical record review; blood collection; and questionnaires on quality of life, nutritional status, and medication adherence. Follow-up visits will occur once a year for at least 3 years or for the duration of the study and will include repeat baseline testing. Participants who have undergone a successful stem cell transplant will attend only one study visit that will include a medical history interview, a medical record review, and quality of life questionnaires.

Study Design

• Study Type: Observational
• Actual Enrollment: 416 participants
• Time Perspective: Prospective
• Official Title: A Longitudinal Cohort Study of Patients With Thalassemia in the Thalassemia Clinical Research Network
• Study Start Date: May 2007
• Actual Primary Completion Date: December 2010
• Actual Study Completion Date: June 2011

Groups and Cohorts

Group/Cohort
Thalassemia cohort; Thalassemia as documented by clinical diagnosis, including: thalassemia (intermedia or major); HbH disease; HbH with non-deletional mutations, e.g., HbH Constant Spring E beta-thalassemia; Homozygous alpha-thalassemia (i.e., 4-gene alpha deletion or equivalent null alpha mutation); Other thalassemic conditions not explicitly excluded; Thalassemia intermedia due to heterozygous beta mutation with alpha-gene excess.
Successful SCT cohort; Individuals who have received a successful hematopoietic SCT, defined as engraftment of all three cell lines and transfusion independence by 100 days post-transplant, for any of the disorders listed above;Monitored for end-organ injury related to thalassemia prior to their successful SCT;Participants who were enrolled in TCRN Registry or had a successful SCT after 01 Jan 2002.

Outcome Measures

Primary Outcome Measures :

1. The prevalence and incidence of complications specific to thalassemia and its treatment among participants [ Time Frame: Measured throughout the duration of the study ]

Secondary Outcome Measures :

1. Fertility and pregnancy outcomes; causes of mortality and changes in mortality risk; genotypic and phenotypic variation; and body iron burden [ Time Frame: Measured throughout the duration of the study ]
2. Relationships among adherence, quality of life, and complications of thalassemia [ Time Frame: Measured throughout the duration of the study ]

Biospecimen Retention:   Samples With DNA

DNA and frozen plasma genetic biorepository

Eligibility Criteria

• Ages Eligible for Study: 5 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes
• Sampling Method: Non-Probability Sample

Study Population

All patients with thalassemia, as documented by clinical diagnosis, seen at sites funded by the Thalassemia Clinical Research Network (TCRN) and their satellites.

Criteria

Inclusion Criteria for People with Thalassemia:

• Thalassemia, as documented by clinical diagnosis, including the following types:

  1. Beta-thalassemia (intermedia or major)
  2. Hemoglobin H (HbH) disease
  3. HbH with non-deletional mutations (e.g., HbH Constant Spring)
  4. E-beta-thalassemia
  5. Homozygous alpha-thalassemia (i.e., 4-gene alpha deletion or equivalent null alpha mutation)
  6. Other thalassemic conditions not explicitly excluded
  7. Thalassemia intermedia due to heterozygous beta mutation with alpha-gene excess
• Requires at least annual monitoring for end-organ injury related to thalassemia, including all clinical measures specified in this study

Inclusion Criteria for People who Have Received a Successful Stem Cell Transplant:

• Received a successful hematopoietic stem cell transplant, defined as engraftment of all three cell lines and transfusion independence by 100 days post-transplant, for any of the thalassemia disorders listed above
• Monitored for end-organ injury related to thalassemia before their successful stem cell transplant, including all clinical measures specified in this study

Exclusion Criteria for People with Thalassemia:

• Has any of the following mild or mixed diagnoses:

  1. Thalassemia trait (i.e., single recessive beta-gene mutation, two-gene alpha-gene mutation)
  2. Thalassemia/Hb S, C, or D compound heterozygotes
  3. HbH with steady state hemoglobin above 9.0 g/dL and no history of significant thalassemia complications (e.g., endocrinopathies, cardiac dysfunction, growth impairment, pulmonary hypertension)
• Unable or unwilling to be followed annually

Contacts and Locations

Locations

United States, California

Children's Hospital of Los Angeles

Los Angeles, California, United States, 90027

Children's Hospital of Oakland

Oakland, California, United States, 94609

Stanford Hospital

Stanford, California, United States, 94305

United States, Georgia

Children's Healthcare of Atlanta

Atlanta, Georgia, United States, 30342

United States, Illinois

Children's Memorial Hospital Chicago

Chicago, Illinois, United States, 60614

United States, Massachusetts

Children's Hospital Boston

Boston, Massachusetts, United States, 02115

United States, New York

Weill Medical College of Cornell University

New York, New York, United States, 10021

United States, Pennsylvania

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States, 19104

United States, Texas

Southwestern Medical Center at Dallas

Dallas, Texas, United States, 75390

Baylor College of Medicine

Houston, Texas, United States, 77030

Canada, British Columbia

British Columbia Children's Hospital

Vancouver, British Columbia, Canada, V6H 3V4

Canada, Ontario

Toronto Sick Kids

Toronto, Ontario, Canada, M5G 1X8

Toronto General Hospital

Toronto, Ontario, Canada, M5G 2C4

United Kingdom

Royal Free and University College London Medical School

London, England, United Kingdom, WC1E 6BT

Sponsors and Collaborators

HealthCore-NERI

National Heart, Lung, and Blood Institute (NHLBI)

Thalassemia Clinical Research Network

Investigators

• Study Chair: Ellis Neufeld, MD, PhD; Boston Children's Hospital
• Study Chair: Janet Kwiatkowski, MD; Children's Hospital of Philadelphia

More Information

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

Trachtenberg FL, Mednick L, Kwiatkowski JL, Neufeld EJ, Haines D, Pakbaz Z, Thompson AA, Quinn CT, Grady R, Sobota A, Olivieri N, Horne R, Yamashita R; Thalassemia Clinical Research Network. Beliefs about chelation among thalassemia patients. Health Qual Life Outcomes. 2012 Dec 7;10:148. doi: 10.1186/1477-7525-10-148.

Morris CR, Kim HY, Trachtenberg F, Wood J, Quinn CT, Sweeters N, Kwiatkowski JL, Thompson AA, Giardina PJ, Boudreaux J, Olivieri NF, Porter JB, Neufeld EJ, Vichinsky EP; Thalassemia Clinical Research Network. Risk factors and mortality associated with an elevated tricuspid regurgitant jet velocity measured by Doppler-echocardiography in thalassemia: a Thalassemia Clinical Research Network report. Blood. 2011 Oct 6;118(14):3794-802. doi: 10.1182/blood-2010-11-319152. Epub 2011 Jul 19.

• Responsible Party: National Heart, Lung and Blood Institute, National Institutes of Health
• ClinicalTrials.gov Identifier: NCT00661804
• Other Study ID Numbers: 568; U01HL065238 ( U.S. NIH Grant/Contract )
• First Posted: April 18, 2008
• Last Update Posted: November 11, 2011
• Last Verified: June 2011

Additional relevant MeSH terms:

Thalassemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn