Study to Collect Data on Fabry Disease Patients With Enhanceable Alpha-Galactosidase A Activity
| Status: | Completed |
|---|---|
| Conditions: | Hematology, Metabolic |
| Therapuetic Areas: | Hematology, Pharmacology / Toxicology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 4/21/2016 |
| Start Date: | March 2005 |
| End Date: | March 2008 |
A Study to Collect Normative Data on Fabry Disease Patients With Enhanceable Alpha-Galactosidase A Activity
This study will collect data needed to design a treatment trial for patients with Fabry
disease using the experimental drug AT-1001. Fabry disease is an inherited metabolic
disorder in which an enzyme called alpha-galactosidase A, which normally breaks down fatty
substances called glycolipids, is missing or does not function properly. As a result,
glycolipids accumulate in various tissues, causing liver, kidney, nerves, skin, muscle and
blood vessel problems. No treatment is given in this survey study.
Males 18 years of age and older with Fabry disease who have certain genetic mutations
associated with enhancement of alpha-galactosidase A activity may be eligible for this
study. Participants undergo the following tests and procedures over 5 days:
Day 1
Medical history and physical examination, blood tests, electrocardiogram (EKG), routine
urinalysis, measurements of height, weight, and vital signs (blood pressure, heart rate,
breathing rate, and temperature).
Day 2
Blood tests, 24-hour urine collection, vital signs and sweat test. The sweat test (also
called QSART, or quantitative sudomotor axon reflex test) measures the amount of sweat in a
particular area of skin. A small amount of medication called acetylcholine is put on an area
of the skin and a small electric current is applied to stimulate the sweat glands.
Day 3
Blood tests, 24-hour urine collection, vital signs, and skin biopsy. For the skin biopsy, a
small area of skin is numbed and a punch device is used to remove a 3-mm (1/8-inch) layer of
skin for microscopic examination.
Day 4
Blood tests, 24-hour urine collection, vital signs, and QSART.
Day 5
Blood tests and vital signs.
In addition to the above, patients are scheduled at some point in the 5-day study for an eye
examination, brain magnetic resonance angiogram (MRA), and a heart examination and
echocardiogram. MRA uses a strong magnetic field and radio waves to provide images of the
blood vessels in the head and neck. It can detect abnormalities such as aneurysms, vessel
malformations, and thickening of the vessel walls. An echocardiogram is an ultrasound test
that shows how well the heart pumps blood and if there is thickening of the heart muscle.
Patients who are taking enzyme replacement therapy discontinue treatment for up to 6 weeks
(no more than two missed infusions) to allow accurate measurement of the amount of
alpha-galactosidase A the patient's body produces by itself. They provide weekly blood
samples between the time they stop treatment and enter the study. The samples are used to
monitor the removal of the enzyme from the body and the possible buildup of Gb(3) in the
blood.
disease using the experimental drug AT-1001. Fabry disease is an inherited metabolic
disorder in which an enzyme called alpha-galactosidase A, which normally breaks down fatty
substances called glycolipids, is missing or does not function properly. As a result,
glycolipids accumulate in various tissues, causing liver, kidney, nerves, skin, muscle and
blood vessel problems. No treatment is given in this survey study.
Males 18 years of age and older with Fabry disease who have certain genetic mutations
associated with enhancement of alpha-galactosidase A activity may be eligible for this
study. Participants undergo the following tests and procedures over 5 days:
Day 1
Medical history and physical examination, blood tests, electrocardiogram (EKG), routine
urinalysis, measurements of height, weight, and vital signs (blood pressure, heart rate,
breathing rate, and temperature).
Day 2
Blood tests, 24-hour urine collection, vital signs and sweat test. The sweat test (also
called QSART, or quantitative sudomotor axon reflex test) measures the amount of sweat in a
particular area of skin. A small amount of medication called acetylcholine is put on an area
of the skin and a small electric current is applied to stimulate the sweat glands.
Day 3
Blood tests, 24-hour urine collection, vital signs, and skin biopsy. For the skin biopsy, a
small area of skin is numbed and a punch device is used to remove a 3-mm (1/8-inch) layer of
skin for microscopic examination.
Day 4
Blood tests, 24-hour urine collection, vital signs, and QSART.
Day 5
Blood tests and vital signs.
In addition to the above, patients are scheduled at some point in the 5-day study for an eye
examination, brain magnetic resonance angiogram (MRA), and a heart examination and
echocardiogram. MRA uses a strong magnetic field and radio waves to provide images of the
blood vessels in the head and neck. It can detect abnormalities such as aneurysms, vessel
malformations, and thickening of the vessel walls. An echocardiogram is an ultrasound test
that shows how well the heart pumps blood and if there is thickening of the heart muscle.
Patients who are taking enzyme replacement therapy discontinue treatment for up to 6 weeks
(no more than two missed infusions) to allow accurate measurement of the amount of
alpha-galactosidase A the patient's body produces by itself. They provide weekly blood
samples between the time they stop treatment and enter the study. The samples are used to
monitor the removal of the enzyme from the body and the possible buildup of Gb(3) in the
blood.
This protocol is designed to characterize the clinical and laboratory profile of patients
with Fabry disease who have residual levels of Alpha-galactosidase (Alpha- Gal A) activity.
Normally these are patients with the later onset or milder forms of the disease, sometimes
referred to as the cardiac and/or renal variants. Enzyme Enhancement Therapy is a novel
therapeutic approach to treatment of lysosomal storage diseases that has recently been
proposed, for patients who produce low levels of endogenous enzyme. We plan to evaluate this
therapy in later-onset Fabry disease patients and in preparation we need to develop
sensitive outcome measures for this subset of patients. Thirty patients with enhanceable
Alpha- Gal A activity will be recruited. If on enzyme replacement therapy, they will be
asked to miss up to two biweekly infusions. These patients, along with five control patients
with non-enhanceable(classic) Fabry disease, will undergo a comprehensive five day
evaluation at the NIH Clinical Center that will include a complete physical examination,
functional studies of the heart, eye, kidney and sweat function, imaging of the brain and
the heart and a number of blood and urine tests, as well as a skin biopsy.
with Fabry disease who have residual levels of Alpha-galactosidase (Alpha- Gal A) activity.
Normally these are patients with the later onset or milder forms of the disease, sometimes
referred to as the cardiac and/or renal variants. Enzyme Enhancement Therapy is a novel
therapeutic approach to treatment of lysosomal storage diseases that has recently been
proposed, for patients who produce low levels of endogenous enzyme. We plan to evaluate this
therapy in later-onset Fabry disease patients and in preparation we need to develop
sensitive outcome measures for this subset of patients. Thirty patients with enhanceable
Alpha- Gal A activity will be recruited. If on enzyme replacement therapy, they will be
asked to miss up to two biweekly infusions. These patients, along with five control patients
with non-enhanceable(classic) Fabry disease, will undergo a comprehensive five day
evaluation at the NIH Clinical Center that will include a complete physical examination,
functional studies of the heart, eye, kidney and sweat function, imaging of the brain and
the heart and a number of blood and urine tests, as well as a skin biopsy.
- INCLUSION CRITERIA:
- Age 18 and older males
- Patients will be included if they possess an Alpha-Gal A mutation that in previous
investigations has been associated with enhancement of enzyme activity, as judged by
the Principal Investigator.
EXCLUSION CRITERIA:
- Patients whose general health prevents them from participating.
- Patients with significant disease unrelated to Fabry disease (e.g. diabetes, cancer).
- Patients who refuse to sign the informed consent form or who are unable to travel to
the NIH Clinical Center.
- Patients who are currently participating in a clinical trial of small molecule or
gene therapy for Fabry disease.
- Patients who are currently participating in a clinical trial for any condition other
than Fabry disease.
- Patients who are judged by the Principal Investigator to be not qualified to
participate.
We found this trial at
1
site
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
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