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

Tracking Information

• First Submitted Date: April 16, 2008
• First Posted Date: April 18, 2008
• Last Update Posted Date: November 11, 2011
• Study Start Date: May 2007
• Actual Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: April 16, 2008): The prevalence and incidence of complications specific to thalassemia and its treatment among participants [ Time Frame: Measured throughout the duration of the study ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 16, 2008)

• 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 ]
• Relationships among adherence, quality of life, and complications of thalassemia [ Time Frame: Measured throughout the duration of the study ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Evaluating People With Thalassemia: The Thalassemia Longitudinal Cohort (TLC) Study
• Official Title: A Longitudinal Cohort Study of Patients With Thalassemia in the Thalassemia Clinical Research Network
• 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.

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 Type: Observational
• Study Design: Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided

Biospecimen

Retention:   Samples With DNA

Description:

DNA and frozen plasma genetic biorepository

• 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.
• Condition: Thalassemia
• Intervention: Not Provided

Study Groups/Cohorts

• 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.

Publications *

• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 22, 2010): 416
• Original Estimated Enrollment (submitted: April 16, 2008): 600
• Actual Study Completion Date: June 2011
• Actual Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 5 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, United Kingdom, United States

Administrative Information

• NCT Number: NCT00661804
• Other Study ID Numbers: 568; U01HL065238 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: National Heart, Lung and Blood Institute, National Institutes of Health
• Original Responsible Party: Same as current
• Current Study Sponsor: HealthCore-NERI
• Original Study Sponsor: National Heart, Lung, and Blood Institute (NHLBI)

Collaborators

• 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

• PRS Account: HealthCore-NERI
• Verification Date: June 2011