A Study of Pyridostigmine in Postural Tachycardia Syndrome
A Study of Pyridostigmine in Postural Tachycardia Syndrome
This is a 3-day study comparing pyridostigmine versus placebo in the treatment of postural
 tachycardia syndrome (POTS). The researchers expect pyridostigmine to improve tachycardia and
 stabilize blood pressure.
The study will be done at the outpatient General Clinical Research Center (GCRC) at Charlton
 7 and will involve two visits. Visit 1 will take about 3 hours, and Visit 2 will occur 2 days
 after Visit 1 and will take about 2 hours.

 You will be put in one of two groups by chance (as in the flip of a coin). One group will be
 taking placebo (an inactive substance), the other group 180 mg pyridostigmine in time release
 formulation. Both placebo and pyridostigmine will look identical and will be taken as one
 capsule per day for 3 days. Neither you nor the study doctor will know at the time of
 treatment whether the treatment being given is active or inactive. However, in case of an
 emergency, this information will be available.

 For each of the two visits, the following tests and procedures will be performed:

 -  When you arrive at the GCRC, you will have a general medical and neurological
 examination and height and weight measurement.

 -  Questionnaires. You will be asked to answer a series of questions on your autonomic
 symptoms (such as rapid heart rate, feeling of tiredness, cold and sweaty hands) at each
 of your two visits. The questionnaire you will be given during your first visit should
 take approximately 30 minutes to complete. The questionnaire you will be given during
 your second visit should take approximately 10 minutes to complete.

 -  Autonomic Reflex Screen. An autonomic reflex screen will be done during each visit. This
 consists of the following:

 -  Quantitative sudomotor axon reflex test (QSART): QSART is a routine clinical test
 that evaluates the response of the sweat gland to a drug, acetylcholine. One
 capsule is placed on your forearm and three on your leg and foot. The testing is
 done by passing a small electrical current, for 5 minutes, to activate the nerves
 that supply the sweat glands. You will feel a slight burning sensation.

 -  Cardiovascular recordings: Blood pressure, heart rate, and other cardiovascular
 measurements will be studied by placing electrodes on the chest and a finger or
 wrist cuff for continuous blood pressure recordings.

 -  Valsalva maneuver: This involves blowing very hard into a bugle (like blowing up a
 balloon) for 15 seconds.

 -  Head-up tilt: Following a period of rest (at least 5 minutes), you will be tilted
 up to an angle of not more than 80 degrees and recordings will be made for up to 30
 minutes. On Visit 1, one hour after you have taken the study medication, this test
 will be repeated. This test will be done only once on Visit 2.

 -  Hormone level measurements: This will be done during each visit. An IV will be
 inserted into a vein in your arm from which approximately one teaspoon of blood
 will be drawn while you are lying down and one teaspoon after standing up. This
 will be repeated only on Visit 1, one hour after the study drug is given. A total
 of four teaspoons of blood will be drawn on Visit 1 and 2 teaspoons will be drawn
 on Visit 2.
Inclusion Criteria:

 Diagnosis of postural tachycardia syndrome using the following criteria:

 -  Orthostatic heart rate increment greater than or equal to 30 beats per minute (bpm)
 within 5 minutes of head-up tilt.

 -  Symptoms of orthostatic intolerance. These include weakness, lightheadedness, blurred
 vision, nausea, palpitations, and difficulty with concentration and thinking.

 Both criteria must be fulfilled.

 Exclusion Criteria:

 -  Pregnant or lactating women

 -  Presence of failure of other organ systems or systemic illness that could affect
 autonomic function or the patient's ability to cooperate with the study

 -  Hypothyroidism or hyperthyroidism

 -  Clinically significant coronary artery disease

 -  Medications that could interfere with autonomic testing

 -  Previous treatment with pyridostigmine for POTS. Patients must not have taken
 pyridostigmine in the past month