Clinical Laboratory Evaluation of Chronic Autonomic Failure

Clinical Laboratory Evaluation of Chronic Autonomic Failure

Background: The autonomic nervous system controls automatic body functions. Researchers want to improve the tests used to diagnose autonomic failure. Orthostatic hypertension is a drop in blood pressure when a person stands up. Researchers want to focus on this sign of autonomic failure. Objective: To improve testing for conditions that cause autonomic nervous system failure. Eligibility: People ages 18 and older in one of these categories: - Their blood pressure drops when they get up. - They have had a heart transplant or bilateral endoscopic thoracic sympathectomies or have had or will have renal sympathetic ablation Design: All participants will be screened with: - Medical history - Physical exam - Blood and urine tests Some participants will be screened with: - Heart and breathing tests - IV placement into an arm vein - Tilt table testing: Participants lie on a table that tilts while an IV is used to draw their blood. Participants may stay in the hospital for up to 1 week depending on their tests. Tests may include repeats of screening tests and: - Sweat testing: A drug is placed on the skin to cause sweating. Sensors on the skin measure moisture. - Lumbar puncture: A needle is inserted between the bones in the back to collect fluid. - MRI and PET/CT scan: Participants lie on a table that slides into a scanner. For the PET/CT, a small amount of a radioactive chemical will be injected with a small amount of a radioactive chemical. - Bladder catheter placement to collect urine - Skin biopsies: A punch tool removes a small skin sample. - Tests to see how the pupils react to light - Smelling tests - Thinking and memory tests - Questionnaires Participants may have a visit about 2 years later to repeat tests.

Pharmaceutical medication involved
Patients and healthy individuals accepted

Drug - Desipramine (DMI)

Desipramine (DMI) is an approved tricyclic antidepressant. The drug inhibits neuronal uptake of catecholamines. DMI treatment is used to test for effects of NET inhibition on results of 11C-MRB or 18F-dopamine PET scans. The subject receives a single dose of DMI by mouth (about 125 mg per 70 kg body mass) about 2-3 hours before the subject receives the PET imaging agent.

Drug - 18F-Dopa

18F-DOPA is a positron-emitting analog of the catechol amino acid, levodopa (L-DOPA, Ldihydroxyphenylalanine). 18F-DOPA PET scanning is used to visualize catecholamine terminals in the brain.

Drug - 11C-methylreboxetine

11C-MRB may be injected IV for visualizing sites of neuronal uptake of norepinephrine in the brain or periphery by PET scanning.

Drug - 13N-Ammonia

13N-labeled ammonia is a perfusion imaging agent used to obtain perfusion-corrected values for 18F-dopamine-derived radioactivity in the heart and other organs.

Drug - 18F-Dopamne

18F-Dopamine is a positron-emitting analog of the catecholamine, dopamine. 18F- Dopamine positron emission tomographic (PET) scanning may be used to visualize sympathetic innervation.

Clinical Laboratory Evaluation of Chronic Autonomic Failure