Pulmonary Disease and Exercise Tolerance in Boys With Fabry Disease

Fabry Disease Clinical Trial

Official title:

Pulmonary Disease and Exercise Tolerance in Boys With Fabry Disease

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01304875
• Other study ID #: CSMC17883
• Secondary ID: U54NS065768
• Status: Recruiting
• Phase: N/A
• First received: February 25, 2011
• Last updated: June 25, 2013
• Start date: April 2010

Study information

• Verified date: June 2013
• Source: Cedars-Sinai Medical Center
• Contact: William R Wilcox, MD, PhD
• Phone: 3104236673
• Email: william.wilcox[@]cshs.org
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Observational

Clinical Trial Summary

When to start children with Fabry disease on therapy is controversial because of its expense and inconvenience. Many Fabry children complain of exercise intolerance. In adults, the investigators have found decreased lung function and ability to exercise on a treadmill. Whether or not lung function and exercise capacity is abnormal in children is unknown. While lung function and exercise tests are commonly part of routine evaluations for adults with Fabry, they are not yet for children.

The objective of the proposed study is to more accurately define the lung and exercise abnormalities in a group of 20 boys from 8-18 years of age with Fabry disease who have not been treated with enzyme replacement therapy (Fabrazyme).

Description:

Fabry disease is due to an alteration in the genetic material (DNA) that causes a deficiency of the alpha-galactosidase A enzyme. This enzyme aids in the breakdown and elimination of certain types of fatty substances called glycolipids. These glycolipids are normally present within the body in most cells. When alpha-galactosidase A is lacking, these glycolipids build up in various tissues such as the eye, liver, kidney, skin, muscle, heart, and blood vessels. The build up of glycolipid levels in these tissues, particularly globotriaosylceramide (GL-3), is thought to cause the clinical symptoms that are associated with Fabry disease. Fabry disease causes chronic kidney damage leading to a need for dialysis or kidney transplantation, chronic heart damage leading to abnormal heart rhythms and heart attacks and strokes at an early age, nervous system damage leading to chronic pain, and a premature death. Because the gene for Fabry is on the X chromosome (men have only one X chromosome while women have two), most patients with symptoms of Fabry are men but many women have symptoms that may be as severe as men. There is currently a FDA approved treatment available that treats many of the symptoms of Fabry, but it involves intravenous infusions every other week and is very expensive.

When to start children on therapy is controversial because of its expense and inconvenience. Children with significant pain or gastrointestinal problems are started on therapy immediately, otherwise not until they are at least teenagers. Increasing evidence suggests that even without overt symptoms, significant, irreversible damage may be occurring in childhood. However, determining whether such damage is present or not requires biopsies. There are no simple measures of disease severity.

Many Fabry children complain of exercise intolerance. In adults, the investigators have found decreased lung function and ability to exercise on a treadmill. Whether or not lung function and exercise capacity is abnormal in children is unknown. While lung function and exercise tests are commonly part of routine evaluations for adults with Fabry, they are not yet for children.

The objective of the proposed study is to more accurately define the lung and exercise abnormalities in a group of 20 boys from 8-18 years of age with Fabry disease who have not been treated with enzyme replacement therapy (Fabrazyme). This will be done by several breathing tests and exercising on a treadmill. If the breathing tests are abnormal, then testing would serve as an easy way to evaluate children and help decide when therapy should be started and monitor the effectiveness of therapy.

Each person that consents to participate in the study will be required to commit to a single study visit that will last approximately 4 hours at Cedars-Sinai Medical Center. The participant will be expected to wear loose fit clothing and comfortable athletic footwear.

As part of the research, participants will be asked to participate in the following tests:

1. A pulmonary function test

2. Exercise test. Results will be forwarded to each participant's primary care physician.

All subjects must have previously been enrolled in the Fabry Registry and have the recommended standard of care assessments in order to be eligible for this pilot study.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 8 Years to 18 Years

Eligibility

Inclusion Criteria:

• Fabry disease

• Male

• Between 8-18 years of age

• Enrolled in Fabry registry and have standard assessments

Exclusion Criteria:

• Enzyme replacement therapy or an experimental therapy

• Inability to perform the tests

• Other, serious medical conditions that would impact the tests

Study Design

Observational Model: Case-Only, Time Perspective: Cross-Sectional

Related Conditions & MeSH terms

• Fabry Disease
• Lung Diseases

Locations

Country	Name	City	State
United States	Cedars-Sinai Medical Center	Los Angeles	California

Sponsors (6)

Lead Sponsor	Collaborator
Cedars-Sinai Medical Center	Genzyme, a Sanofi Company, National Center for Advancing Translational Science (NCATS), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institute of Neurological Disorders and Stroke (NINDS), Rare Diseases Clinical Research Network

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Measurement of pulmonary function	Research subjects' pulmonary function will be determined by FEF25-75, VO2 max, and treadmill studies.	upon enrollment
Secondary	Measurement of diastolic blood pressure	The maximum decrease in diastolic blood pressure with exercise will be compared to baseline diastolic blood pressure.	upon enrollment

External Links

•   Rare Diseases Network