This study will conduct laboratory tests and administer various drugs to patients with primary chronic autonomic failure (CAF) to learn more about these disorders. The autonomic nervous system regulates many (automatic) body functions, such as blood pressure and pulse rate. In most patients with abnormalities of autonomic function, the cause of the dysfunction is not known. This is called primary CAF . Primary CAF includes pure autonomic failure; multiple system atrophy; Parkinson's disease with autonomic failure; and autoimmune autonomic neuropathy.

Healthy normal volunteers and patients with primary CAF who are 18 years of age or older may be eligible for this study. Candidates will be screened with a medical history, physical examination, and possibly a neurological examination. Participants will be admitted to the NIH Clinical Center for about a week of tests, which will be from among those listed below. Participants will give their consent for each test individually.

- Arterial catheter: insertion of a catheter (plastic tube) into an artery in the elbow crease for continuous blood pressure measurement.

-Bladder catheter (patients only): insertion of a catheter into the bladder before PET scanning (see below) in patients who have urinary problems in order to protect the patient and others from radioactivity.

- Bladder motility (patients only): ultrasound (sound wave) examination of bladder function.

- Blood drawing: collection of blood samples through the arterial catheter (see above). The total amount of blood collected does not exceed 225 milliliters (15 tablespoons).

- Blood flows: measurement of blood flow in the forearm or calf using sensors applied to the skin and a blood pressure cuff around the limb. To measure limb blood flow, the pressure cuff is blown up and the air released several times.

- DNA extraction and storage (patients only) - collection of a blood sample for extracting and storing DNA for future studies of primary CAF and other disorders, as permitted by the subject.

- Echocardiogram: ultrasound test of the heart.

- Electrocardiogram (EKG): test of the electrical activity of the heart, using electrodes (sensors) applied to the skin of the chest and limbs.

- Environmental temperature manipulation: test of responses to changes in temperature. Watertight pads are applied to the back and front of the body. Warm water and then room temperature water are passed through the pads and body temperatures are measured.

- Gastrointestinal motility (patients only): recording of bowel sounds using a microphone placed on the abdomen.

- Lower body negative pressure (LBNP): test of autonomic function in which the lower body is placed in a barrel-like chamber. The barrel is made airtight, using a Plexiglas shield, rubberized sheeting, and duct tape, and some air is sucked out of the barrel with a vacuum cleaner. This causes blood to pool in the legs, as occurs during standing. LBNP is done for about 15 minutes at a time.

- Lumbar puncture (spinal tap): test done to obtain spinal fluid for chemical tests. A local anesthetic is given and a needle is inserted in the space between the bones in the lower back where the CSF circulates below the spinal cord. A small amount of fluid is collected through the needle.

- Microdialysis: test to measure levels of chemicals in particular tissues, such as the fatty tissue under the skin.

- PET scanning: type of nuclear medicine scan that uses a radioactive drug, x-rays, and computer technology to create images of body organs.

- Pupillometry: test of the size of the pupil of the eye, measured by using a special digital camera in a light-controlled room, with the lights of and the lights on.

- Quantitative sudomotor axon reflex test (QSART): diagnostic test of a particular aspect of autonomic nervous system function. A small amount of a brain chemical called acetylcholine is applied to the skin with a tiny amount of electricity. The sweat in a nearby patch of skin is measured by following the amount of humidity in a chamber applied to the skin.

- Salivation: measurement of how much saliva a person produces. A piece of cotton-like material is placed between the teeth and gums. As the material absorbs saliva, its weight increases and the material is weighed to measure the amount of saliva produced.

- Skin electrical conduction: test of sweat production. Sweat conducts electricity, so changes in sweating can be measured by the resistance of the skin to the flow of electricity. This is done with sensors placed on the skin.

- Skin and core temperature: tests for measuring body core temperature and skin temperature. Skin temperature is measured with sensors placed on the skin, and core temperature is measured with sensors in a cotton ball that is placed in the ear canal against the eardrum.

- Speech and swallowing assessment (patients only): testing by rehabilitation medicine specialists for patients with speech and swallowing difficulties.

- Stress echocardiogram: test of the heart's response to exercise stress. A catheter is placed in the subject's arm for sampling blood or giving a drug during the bicycle-type exercise. While the subject exercises, blood pressure, pulse rate, and EKG are continuously monitored.

Various drugs may be administered during the above tests, including chemical messengers such as acetylcholine, epinephrine and norepinephrine; radioactive chemicals drugs in imaging studies, drugs to examine specific mechanisms in autonomic failure, drugs that affect blood vessels, heart rate, and force of heart contractions; and drugs that affect the skin, glands, bowel motility, urinary bladder tone, and salivation.

Condition	Treatment or Intervention
Autonomic Nervous System Diseases	Drug: Acetylcholine  Drug: (3) H-Epinephrine  Drug: 6-[18F] Fluorodopa  Drug: 6-[18F] Fluorodopamine  Drug: (3) H-Norepinephrine  Drug: Trimethaphan  Drug: Tyramine  Drug: Yohimbine  Drug: Trospium Chloride  Drug: 13N-Ammonia

Further Study Details: 

Expected Total Enrollment:  125

In dysautonomias, altered function of the autonomic nervous system adversely affects health. Primary abnormalities of autonomic function have been classified clinically into different chronic autonomic failure (CAF) syndromes. This protocol calls for comprehensive evaluation of autonomic function, using physiological, neuropharmacologic, neurochemical, and neuroimaging approaches, to identify lesion types and sites in CAF and thereby improve the diagnosis and understanding of pathophysiologic mechanisms of CAF.

Genders Eligible for Study:  Both

Accepts Healthy Volunteers

Criteria

INCLUSION CRITERIA:
The subjects are patients with known or suspected primary CAF, based on referral information and confirmation of the clinical diagnosis at the intake evaluation.
Participation in this protocol is offered to people 18 years old or older, independently of gender, race, age, ethnicity, religion, or any other demographic or sociopolitical classifications.
Control patients have previously diagnosed PD or MSA without orthostatic hypotension, confirmed at the time of the intake evaluation.
EXCLUSION CRITERIA:
People younger than 18 years old are excluded. Advanced age does not constitute an exclusion criterion.
A candidate subject is excluded if, in the judgment of the Principal Investigator or Clinical Director, protocol participation would place the subject at substantially increased acute medical risk. This includes the risks associated with air travel to the NIH. A candidate subject is excluded if, in the opinion of the Principal Investigator or Clinical Director, the medical risk outweighs the potential scientific benefit.
A candidate subject is excluded if there is a disqualifying condition. Examples of disqualifying conditions are hepatic or renal failure, symptomatic congestive heart failure, severe anemia, psychosis, refractory ventricular arrhythmias, and symptomatic coronary heart disease. A positive HIV test result does not necessarily exclude a patient from participating. Patients are excluded from further participation if the results of the intake evaluation lead to a diagnosis of a secondary form of CAF, such diabetic autonomic neuropathy. If a patient has a history of glaucoma, then an ophthalmology consult will be obtained, to determine whether exposure to any of the procedures or test drugs would place the patient at undue risk. If so, then the patient will be excluded from the study.
A candidate subject is excluded if clinical considerations require that the patient continue treatment with a drug likely to interfere with the scientific results. An example would be treatment with a tricyclic antidepressant. Patients with known or suspected allergy or hypersensitivity to any test drug are excluded from receiving that drug. Patients who must take medications daily in the following categories are excluded: anticoagulants, tricyclic antidepressants, barbiturates, aspirin, or acetaminophen. Patients unable to discontinue nicotine or alcohol temporarily are excluded. Patients are not to discontinue any medications before the patient or the patient's doctor discusses this with Dr. Goldstein, the Principal Investigator, or Sandra Brentzel, the Research Nurse. If it is decided that discontinuing medications would be unsafe, then the patient is excluded from the study. Subjects must discontinue use of alcohol and tobacco throughout the period of testing in the protocol.
Herbal medicines or dietary supplements must be discontinued before enrollment in the study. In cases where the subjects wish to continue their herbal medicines or dietary supplements while on study, and search of the available medical literature fails to identify effects that are known or expected to interfere with the experimental results, then the subjects may participate.
Patients in whom we feel it would be difficult to insert a catheter into a vein are excluded. Subjects who are not expected clinically to tolerate lying still during the procedures are excluded.
Pregnant or lactating women are excluded. Women of childbearing potential must have a negative urine or blood test for pregnancy done within 24 hours before any testing involving radioactivity.
Investigators may also exclude a subject from further participation, such as in the event of known or suspect falsification of medical history information or refusal to undergo planned tests or procedures, without loss of benefits to which the subject was previously entitled.

Maryland
      National Institute of Neurological Disorders and Stroke (NINDS), 9000 Rockville Pike,  Bethesda,  Maryland,  20892,  United States; Recruiting

Study ID Numbers:  030004; 03-N-0004
Record last reviewed:  March 22, 2004
Last Updated:  November 23, 2004
Record first received:  April 16, 2003
ClinicalTrials.gov Identifier:  NCT00059033
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08