Catecholamine Reserve and Exercise Tolerance in Healthy Volunteers and Patients With Congenital Adrenal Hyperplasia
Information source: National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov processed this data on August 20, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Congenital Adrenal Hyperplasia; Healthy
Phase: N/A
Status: Completed
Sponsored by: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Summary
This study will examine and compare the effects of intense exercise on the release of
catecholamines in patients with congenital adrenal hyperplasia (CAH) and in healthy persons.
Catecholamines are hormones (adrenaline and noradrenaline) that are produced by the adrenal
glands and released into the blood stream during stress, such as trauma, illness, intense
exercise, or low blood sugar. The study will also assess exercise tolerance in patients
with CAH, compared with healthy persons.
Patients with CAH between the ages of 10 and 40 years who are managing well on standard
treatment (glucocorticoids, mineralocorticoids) may be eligible for this study. Healthy
volunteers that match the enrolled patients in age, sex, race and body fat will be recruited
as control subjects. All candidates will be screened with a medical history, physical
examination and electrocardiogram (EKG). Body fat will be measured using an instrument
called a Bod Pod. The body fat measurement has two parts: first, the subject sits quietly
in a large egg-shaped capsule for about 2 to 3 minutes; then the subject breathes into a
plastic tube for one minute, followed by three quick panting breaths. Women will have a
urine pregnancy test; pregnant women cannot participate in the study.
Participants will undergo three exercise sessions on separate consecutive mornings after
fasting overnight. Before each test, patients (not healthy volunteers) will take either an
additional morning dose of hydrocortisone or a placebo (a lookalike pill with no active
ingredient). Before each test a thin catheter (plastic tube) will be placed into an arm
vein through a needle. A numbing cream can be applied to make the needle stick hurt less.
Blood will be drawn through this intravenous (IV) line before, during and after the exercise
tests. The first test is a maximal exercise test to determine the individual's maximum
exercise fitness capacity. The second two and third tests are a standardized exercise
tests. Before the two standardized tests, patients (not healthy volunteers) will take
either an additional morning dose of hydrocortisone or a placebo (a lookalike pill with no
active ingredient). All tests are done on a stationary bicycle.
Maximal Exercise Test - The subject pedals on a stationary bicycle for about 10 minutes.
After a 3-minute warm-up, the workload is increased continuously until either the subject
can no longer continue or the physician stops the test for medical reasons. During the
exercise, heart rate and heart activity are monitored with an EKG, and the subject wears a
nose clip and mouthpiece connected to a breathing tube to measure oxygen use. Blood is
drawn before and during the test, totaling no more than 2 tablespoons.
Standardized Exercise Test - The subject pedals on a stationary bicycle for 20 minutes,
while wearing the nose clip and mouthpiece to measure oxygen use. For the first 5 minutes,
the subject pedals at a speed that elicits 50 percent of maximal effort (determined by the
maximal exercise test); the next 10 minutes are at 70 percent of maximal effort; and the
last 5 minutes are at 90 percent. Blood samples drawn before, during (at 15 and 20 minutes)
and after exercise (at 30, 40 and 60 minutes) total less than 1/2 cup. Heart rate and heart
activity are monitored during the test with an EKG, and temperature is measured before and
at the end of the test.
Clinical Details
Official title: Catecholamine Reserve and Exercise Tolerance in Subjects With Congenital Adrenal Hyperplasia and Healthy Controls
Study design: N/A
Detailed description:
Congenital adrenal hyperplasia (CAH) denotes a family of inherited disorders with defects in
the cortisol biosynthesis. CAH has been traditionally considered a disease restricted to
the adrenal cortex. However, recently observed abnormal adrenomedullary structures in three
adrenalectomized patients with classic CAH, as well as low baseline urinary and plasma
epinephrine levels in children with CAH suggest that this condition is associated with
marked morphological and functional abnormalities of the adrenal medulla.
The adrenal medulla synthesizes and secretes catecholamines, mainly epinephrine.
Catecholamines influence virtually all tissues. Yet, the clinical implications of
epinephrine deficiency in humans are not clear.
Short-term intense exercise is a natural, quantifiable stimulus of the adrenal cortex and
medulla as well as of the sympathetic nervous system. We would like to employ a standard
cycle ergometer exercise protocol to study the adrenomedullary and systemic sympathetic
function of patients with CAH. This protocol has been run by the Clinical Center
Rehabilitation Medicine Department (RMD) for 10 years. No serious adverse effects have been
observed or reported in adults and children with a healthy cardiovascular system.
The goal of this protocol is to evaluate adrenomedullary and systemic sympathetic function
and exercise tolerance in patients with CAH and in appropriately matched healthy controls
using the above standardized cycle ergometer test. Subjects with CAH will exercise with and
without doubling their morning dose of hydrocortisone to evaluate whether impairments - if
present - can be corrected by a "stress dose" of hydrocortisone. We hypothesize that
subjects with CAH have a reduced epinephrine reserve and impaired exercise tolerance, which
can at least partially, be corrected by an increase in exogenous hydrocortisone. We will
also determine whether the systemic sympathetic nervous system compensates for the
adrenomedullary deficiency as observed in states of acquired adrenal insufficiency. The
results of this study will increase the understanding of the physiologic interactions
between adrenal cortex and adrenal medulla.
Eligibility
Minimum age: 9 Years.
Maximum age: 40 Years.
Gender(s): Both.
Criteria:
- INCLUSION CRITERIA:
Age: 9-40 years.
CAH patients on conventional therapy (glucocorticoids, mineralocorticoids) in good
clinical management as defined by the following criteria:
1. 17-OH-progesterone level between 100 and 1500 ng/dL;
2. Plasma renin activity normal;
3. Growth rate within 2 SD for age (children);
4. No new signs or symptoms of virilization (clitoral growth, voice deepening) for
females.
Healthy volunteers will be matched for age, sex, race and body fat.
EXCLUSION CRITERIA:
Inability to understand or comply with instructions related to the study (as judged by
investigator).
Chronic medical conditions other than congenital adrenal hyperplasia except mild
conditions (e. g. allergic rhinitis, migraine headaches) will be excluded provided the
subjects are not acutely ill and do not require medication for this condition during the
study.
Acute medical conditions including intercurrent infection and fever in the preceding 7
days.
Positive pregnancy test.
CAH patients on flutamide.
Tylenol or other acetaminophen-containing medicines (e. g. over-the-counter cold medicines)
within 5 days before each test period.
Caffeine, alcohol or strenuous exercise within 24 h before each test period.
Current smokers.
Locations and Contacts
National Institutes of Health Clinical Center, 9000 Rockville Pike, Bethesda, Maryland 20892, United States
Additional Information
Related publications: Albert CM, Mittleman MA, Chae CU, Lee IM, Hennekens CH, Manson JE. Triggering of sudden death from cardiac causes by vigorous exertion. N Engl J Med. 2000 Nov 9;343(19):1355-61. Borg GA. Psychophysical bases of perceived exertion. Med Sci Sports Exerc. 1982;14(5):377-81. Axelrod J, Reisine TD. Stress hormones: their interaction and regulation. Science. 1984 May 4;224(4648):452-9. Review.
Starting date: February 2001
Last updated: May 11, 2011
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