Circulating Transforming Growth Factor Beta (TGF-β) in Individuals With Marfan Syndrome

Circulating Transforming Growth Factor Beta (TGF-β) in Individuals With

Transforming Growth Factor Beta (TGF-β) is a protein that controls proliferation, cellular differentiation, and other functions in most cells. TGF-β levels play a major role in the pathogenesis of Marfan syndrome, a disease characterized by disproportionate height, long extremities, lens dislocation in the eyes and heart complications such as mitral valve prolapse and aortic enlargement increasing the likelihood of aortic dissection. While the underlying defect in Marfan syndrome is faulty synthesis of the glycoprotein fibrillin I, normally an important component of elastic fibers it has been shown that the Marfan syndrome phenotype can be relieved by addition of a TGF-β antagonist in affected mice.

Study Overview

• Status: Withdrawn
• Conditions: Marfan Syndrome
• Intervention / Treatment: Other: Blood draw

Detailed Description

Transforming Growth Factor Beta (TGF-β) is a protein that controls proliferation, cellular differentiation, and other functions in most cells. TGF-β levels play a major role in the pathogenesis of Marfan syndrome, a disease characterized by disproportionate height, long extremities, lens dislocation in the eyes and heart complications such as mitral valve prolapse and aortic enlargement increasing the likelihood of aortic dissection. While the underlying defect in Marfan syndrome is faulty synthesis of the glycoprotein fibrillin I, normally an important component of elastic fibers it has been shown that the Marfan syndrome phenotype can be relieved by addition of a TGF-β antagonist in affected mice. This suggest that while the symptoms of Marfan syndrome may seem consistent with a connective tissue disorder, the mechanism is more likely related to reduced sequestration of TGF-β by fibrillin.

• Study Type: Interventional
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60614
      • Children's Memorial Hospital Chicago

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 24 years (ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Individual with Marfan syndrome consented in to the Main Atenolol Vs. Losartan NIH study.

Exclusion Criteria:

• Subjects in the main PHN Marfan trial who have not achieved the maintenance drug dosing or who have stopped taking study drug.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To determine if circulating levels of TGF-β correlate with treatment arms: Atenolol vs. Losartan.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To determine if circulating levels of TGF-β correlate with clinical outcomes within a treatment group or independent treatment groups.	These clinical outcomes may be a change in aortic root Z-score, final aortic root dimension, final aortic root Z-score and other clinical outcomes in the main Marfan trial.	1 year

Collaborators and Investigators

• Sponsor: Ann & Robert H Lurie Children's Hospital of Chicago
• Collaborators: Johns Hopkins University

Study record dates

Study Major Dates

• Study Start: April 1, 2011
• Primary Completion (ACTUAL): December 1, 2014

Study Registration Dates

• First Submitted: May 25, 2011
• First Submitted That Met QC Criteria: May 25, 2011
• First Posted (ESTIMATE): May 26, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): February 5, 2016
• Last Update Submitted That Met QC Criteria: February 4, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Keywords: TGF-B blood levels Atenolol vs, Losartan Study, NIH, NIHLB and NMF
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Disease; Congenital Abnormalities; Genetic Diseases, Inborn; Musculoskeletal Diseases; Connective Tissue Diseases; Bone Diseases; Heart Defects, Congenital; Cardiovascular Abnormalities; Musculoskeletal Abnormalities; Abnormalities, Multiple; Bone Diseases, Developmental; Limb Deformities, Congenital; Syndrome; Marfan Syndrome; Arachnodactyly
• Other Study ID Numbers: IRB # 2011-14507

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED