What is the purpose of this study?
The purpose of this study is to obtain information on the effects that the drug dichloroacetate (DCA)
has on physical fitness of patients with congenital lactic acidosis (CLA)/mitochondrial myopathies.
Information about fitness will be compared between persons who do and do not have CLA.
Who can participate in this study?
We would like to recruit patients with CLA who are between the ages of 12-55 years old. You must have a
minimum height of 130 cm (51.5 inches). Other eligibility criteria are outlined below. Your family
physician and members of the research team will determine if you are eligible for this study.
Inclusion Criteria: (1) Biochemical or molecular proof of a defect in pyruvate dehydrogenase or one or
more respiratory chain enzymes, or defective pyruvate oxidation to CO2, as determined in cultured
fibroblasts, lymphocytes, or other biopsy material, and (2) Sufficient neurological and neuromuscular
development to perform a graded exercise test and a 15-minute bout of moderate intensity exercise on a
stationary bicycle or treadmill.
Exclusion Criteria: (1) Hyperlactatemia associated with proven biotinidase deficiency
(biotin-responsive CLA) or with enzyme deficiencies of gluconeogenesis, and (2) Primary disorders of
amino acid or fatty acid metabolism, and (3) Malabsorption syndromes associated with D-lactic acidosis,
and (4) Renal insufficiency, defined as a requirement for chronic dialysis (any cause) or a serum
creatinine > 1.2 mg/dl and a creatinine clearance less than 60 ml/min, and (5) Primary hepatic disease
unrelated to CLA, and (6) Women of child bearing age who are pregnant, or who are planning to become
pregnant during the study.
What will be done if you take part in this research study?
If you agree to take part in this study, now and again at 3 months, you will undergo exercise testing
over 6 or 7 days at the General Clinical Research Center (GCRC) at Shands Hospital at the University of
Florida. We will need to sample your blood frequently throughout the study. We will obtain frequent
amounts of blood by placing a small plastic tube in your arm. You should wear light exercise clothing
for all of the exercise sessions. For 2 of the exercise tests you will receive the drug dichloroacetate
(DCA), and for 2 other exercise tests you will receive an inactive substance called a placebo. These
are called the “study treatments”. A placebo is a substance that looks like and is given in the same
way as a treatment but contains no medicine, for example, a sugar pill. You will not know when you are
receiving DCA or placebo. A placebo is used in research studies to show what effect a treatment has
compared with taking nothing at all. After the first 3 test sessions, there will be 1 day to rest when
you will not exercise. After all the exercise tests are completed, you will take DCA every day at home
for a period of 3 months. After those 3 months, the exercise tests will be repeated over a 3 day period
at the GCRC. A brief description of the study protocol is given below.
Day 1 - Orientation. During this session we will measure your height, weight, and the thickness of
certain areas of your skin (body composition). You will fill out 3 questionnaires that ask about your
characteristics, about your past and present health, about your physical activity habits, and about how
you feel and how well you are able to do your usual activities. Finally, you will practice riding a
stationary bicycle or walking on a treadmill. You will also practice wearing headgear, a mouthpiece,
and a nose clip. This equipment is used to measure your fitness level.
Day 2 - Exercise Test. During this test we will take blood samples throughout the day. You will
receive one of the study treatments in the morning. After about 1 hour, you will exercise on the
stationary bicycle or treadmill while the intensity of exercise is gradually increased to the point where
you feel too tired to continue.
Day 3 - Exercise Test. During this test we will take blood samples throughout the day. You will
receive one of the study treatments in the morning. After about 1 hour, you will exercise on the
stationary bicycle or treadmill at a moderate level for 15 minutes.
Day 4 – Rest Day. You will not exercise on this day. We will determine the function of your nerves by
performing a nerve test. An electrode will be placed on the skin over a muscle and the nerve under the
skin will be stimulated by a small shock. This shock is very mild and should not be painful. The time
it takes for your muscle to contract will be measured.
Days 5 and 6 – Exercise Tests. You will receive the other study treatment on both of these days and
perform the exercise tests like you did on days 2 and 3.
Remainder of the study. Once Session 6 is over, you will take DCA by mouth every day at home for 3
months. After the 3 months, the following tests will be repeated: body composition, questionnaires,
the exercise testing from Sessions 2 and 3, and the nerve test.
What other information is available on this website?
This website was designed to provide you with information about the DCA/CLA Clinical Trial conducted on
the GCRC at the University of Florida. This page contains an abundance of information for families and
physicians. You can learn more about DCA, CLA, and travel arrangements to the GCRC by following the
links on the CLA-DCA homepage.
Who can I contact if I need more information about this study?
ENROLLMENT FOR THIS PROTOCOL HAS CLOSED
If you need more information or have questions about this study, you can contact the people listed
below.
Glen E. Duncan, Ph.D.
JHMHC Box 100226
Gainesville, FL 32610-0226
Tel: (352) 392-2321
Fax: (352) 846-0990
gduncan@ufl.edu
Peter W. Stacpoole, Ph.D., MD
JHMHC Box 100226
Gainesville, FL 32610-0226
Tel: (352) 392-2321
Fax: (352) 846-0990
stacpool@gcrc.ufl.edu
Margaret Francis, ARNP
Clinical Coordinator
JHMHC Box 100277
Gainesville, FL 32610-0277
Tel: (352) 392-2321
Fax: (352) 846-0990
francma@medicine.ufl.edu
Heather Barbour, Nursing Manager
Clinical Research Center
JHMHC Box 100322
Gainesville, FL 32610-0322
Tel: (352) 395-0032
Fax: (352) 338-9843
hbarbour@gcrc.ufl.edu
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