The following is a copy of the Consent Form For Patients from the NIH Study described below. It has been scanned from originals provided by the NIH and permission to reproduce it here has been granted by Dr. David Goldstein, who is running the study. While all attempts have been made to reproduce the text as accurately as possible, typographical errors may exist and for this we apologize. In addition, we have changed the formatting for the document to turn it into this Web page. Comments on the Web page may be sent to: Webster, the RSDNet Tech Staff. Questions about the study must be addressed to the NIH.

STUDY TITLE: Positron Emission Tomographic (PET) Scanning of Sympathetic Innervation and Function in Patients with Neurocardiologic Disorders
INSTITUTE: National Institute of Neurological Disorders and Stroke
STUDY NUMBER: 94-N-186
PRINCIPAL INVESTIGATOR: David S. Goldstein, MD, Ph.D.

INTRODUCTION

We invite you (or your child) to take part in a research study at the National Institutes of Health. It is important that you read and understand several general principles that apply to all who take part in our studies (a) taking part in the study is entirely voluntary; (b) personal benefit may not result from taking part in the study, but knowledge may be gained that will benefit other; (c) you may withdraw from the study at any time without penalty or loss of any benefits to which you are otherwise entitled. The nature of the study, the risks, inconveniences, discomforts, and other pertinent information about the study are discussed below. If you have personal, religious or ethical beliefs which you think might limit the type of medical treatment (for example, blood transfusions) that you would agree to receive (or would want your child to receive), you should discuss them fully with your NIH physicians (or appropriate members of the research team). You are urged to discuss any questions you have about this study with the staff members who explain it to you.

CONSENT FORM FOR PATIENTS

WHAT THIS STUDY IS ABOUT

This study is about a new technique to see and measure the activity of the body's most rapidly acting and powerful "stress" system--the sympathetic nervous system. When you are frightened or angry or when you stand up and exercise, the activity of the sympathetic nervous system rapidly increases, maintaining the correct supply of blood and fuel to the body's organs. The sympathetic nervous system is responsible for producing most of the bodily signs of stress, such as sweating, fast and forceful heartbeat, and pale skin. All the visible signs of shock are due to drastic stimulation of the sympathetic nervous system, in a last-ditch effort to maintain vital bodily functions; and when the system gives way, the organism dies.

The existence and importance of the sympathetic nervous system have been known for many years. The difficulty has been in seeing it and measuring its activity. This is because the system consists of millions of tiny nerve endings in the heart and other organs as well as in mesh-like networks in the walls of blood vessels. In this study, we should be able to visualize the location and function of sympathetic nerves in the various organs of the body, to determine the effects of various drugs or stressors on the system, and to suggest how the activity of the system may change during various disorders.

We are asking you to participate in this study because you may have one of the following disorders: (1) clinical findings such as chest pain that suggest coronary artery disease; (2) decreased heart function; (3) high blood pressure; or (4) known or suspected abnormalities of the autonomic nervous system. which is a general term to describe the portion of the nervous system involved with involuntary activities of glands and internal organs.

All these conditions may involve abnormal function of the sympathetic nervous system in the heart.

The basis for visualization of sympathetic nerves in this study is PET scanning after injection of positron-emitting fluorodopamine. "PET" stands for "positron emission tomography". Imagine you had a radioactive object in a box. You could determine if there were something radioactive inside by using a detector, such as a Geiger counter. Now imagine that you had many little Geiger counters all around the box. Each counter would detect a different amount of radioactivity, depending on the shape of the object and the distance of the counter from the object. If you had a way to construct a picture, such as in a newspaper photo, where the size and intensity of each dot depended on the amount of radioactivity, then you could construct an image of the object inside the box. Tomographic scans are two-dimensional images, or slices. Tomographic slices would allow you to see what was inside the box at any level. If the object were small, most of the slices would be empty. Eventually, at the level of the object, you would see an image of the object in the slice.

A positron emitter is a type of radioactive substance that releases a form of radiation that can penetrate the body and reach detectors outside it, enabling construction of a "PET scan" Other "scans" used in nuclear medicine use a somewhat different source of radioactivity, but the idea is about the same.

Fluorodopamine is a drug that is structurally similar to the biochemicals of the sympathetic nervous system, noradrenaline and adrenaline. Just as some radioactive chemicals get taken up by bone, producing a bone scan, or get taken up by the brain, producing a brain scan, fluorodopamine gets taken up into sympathetic nerve endings, and the result is a scan of the sympathetic nervous system. For instance, we know that fluorodopamine gets taken up very readily into the heart walls, because there are so many sympathetic nerve endings there. Because there are so many sympathetic nerve endings in the heart, PET scans of the heart after injection of fluorodopamine basically look like images of the heart itself.

SCREENING, EXCLUSIONS, AND PAYMENT

Before being accepted into the protocol, you will undergo a screening medical history and physical examination, tests of blood and urine, an echocardiogram, and an electrocardiogram. It is possible that results of the screening evaluation will exclude you from participating in the study. Patients in whom technical problems preclude insertion of an antecubital venous (and in most cases an arm arterial) catheter will also be excluded. If you are a women of child-bearing age, pregnancy must be excluded before you can participate in this protocol. This will be done as part of the screening testing of urine. Some other findings may exclude you from particular portions of this study, as discussed later in this consent form.

You may be asked to discontinue medications, such as for high blood pressure, for two weeks before the testing. Do not discontinue any medications before you or your doctor discuss this with Dr. Goldstein, the Principal Investigator for this study, or one of the cardiologists who are Associate Investigators for this study. If it is decided that discontinuing your medications would be unsafe, then you may be excluded from the study.

You will not be paid for participating in this study, because you are likely to benefit personally from the information provided by the study, you are being followed at an NIH clinic, or you are receiving prescription drugs through the NIH.

A TYPICAL TESTING SESSION

BECAUSE OF THE SEVERAL POSSIBLE TREATMENTS AND PROCEDURES THAT YOU MAY RECEIVE OR UNDERGO IN THIS PROTOCOL, A CHART INCLUDING THE PLANNED TREATMENTS AND PROCEDURES IN YOUR PARTICULAR CASE IS ATTACHED TO THIS CONSENT FORM.

A typical PET scanning session takes place over the course of most of a morning and into the afternoon.

On the morning of the study, you report to a special observation room in the PET scan area of the Nuclear Medicine Department in the Clinical Center. Do not smoke cigarettes or drink alcohol, take in any food or drink containing caffeine, or drink any decaffeinated coffee or tea for at least 18 hours before reporting for the testing. Do not take any aspirin for at least 5 days and acetaminophen (Tylenol™) for at least 1 day before the testing. If the procedure is delayed, you may take a light breakfast.

After you urinate to empty your bladder, electrocardiographic (EKG) leads will be attached to your chest, in order to monitor your heart rate and rhythm. Then you will undergo insertion of one or possibly two intravenous ("i.v.") catheters and probably an arterial catheter in the elbow area. The arterial catheter is described in detail below.

You will then be brought into the PET scanning room and lay down on an X-ray type table, which slides you into the hole of the doughnut-shaped scanner. You will be in the scanner for a few hours, and you may become bored. If you wish, you may bring a portable cassette recorder and listen to quiet music via earphones during the testing session.

In most cases, the chest will be in the PET scanner. In cases where we are evaluating an arm rather than the he art, your arm would be in the scanner, or a device like a Geiger counter will be used to record total radioactivity in an area of the limb, without PET scanning. In a few cases, the abdomen rather than the chest will be in the scanner.

Most patients to be studied under this protocol will undergo insertion of an arterial catheter.

An arterial catheter looks like a regular i.v. tube, and it is inserted in about the same place-the elbow crease area or sometimes the wrist area--but the tube is inserted into an artery, not a vein. Arteries carry the blood pressure, and if an arterial catheter is in place, we can measure your blood pressure continuously. The main other reason for inserting an arterial catheter as part of this testing is to enable us to draw blood samples rapidly, repeatedly, and without causing you pain. Because of the high pressure, and the fact that arteries cannot be seen in the skin, certain special procedures are involved. First, the skin is numbed with a local anesthetic, so that you don't feel pain when the catheter is inserted. Second, every so often the catheter will be flushed with a dilute anticoagulant solution, which prevents clogging of the catheter with a blood clot. Third, after the catheter is removed, local pressure will be applied for 10 minutes to prevent bleeding under the skin. And fourth, the area will be clean and the catheter will be in for a minimal period of time, to prevent infection. None of these complications, or any other serious complication, has occurred in over 150 arterial catheter insertions we have done since about 1980.

The patch of skin where the arterial catheter will be inserted will be numbed with lidocaine, a "caine" type of local anesthetic. The catheter at first surrounds an even thinner needle. After the needle is in the artery' the tube is passed over the needle into the artery and the needle removed, so that all that is left in the artery is the plastic tube. The arterial catheter is about 2 inches long. You should feel either nothing or else a slight pressure when the catheter is placed. A very similar plastic tube will be placed in an arm vein; the i.v. will be used to inject the fluorodopamine.

After the i.v. catheter is in place, fluid will be passed through at a slow rate.

After about 20 minutes of rest, baseline blood samples will be drawn from the arterial catheter.

Once you are placed in the scanner, and you are in a comfortable position, you will not be allowed for a few hours to twist or turn the part of the body in the scanner. In most cases, your chest will be in the scanner. You will be allowed to move body parts outside the scanner, such as the head or feet. You may be fed or drink through a straw while you are in the scanner.

A preliminary "attenuation scan" will be obtained. The attenuation scan, which lasts several minutes, enables us to check whether the heart (or other organ of interest) is positioned correctly in the field of the scanner's view. The attenuation scan is also needed for appropriate analysis of the scanning results after injection of the fluorodopamine.

Positron-emitting fluorodopamine will then be injected during an interval of a few minutes. In most cases, the injection will be i.v. You should not feel anything unusual due to the fluorodopamine injection. After the injection, PET scanning will be done for up to 3 hours. It is possible that another scan will be obtained after this period-either another attenuation scan or a scan after injection of a perfusion imaging agent (described below).

Some people have an urge to urinate after lying down for a few hours. If you feel an urge to urinate during the PET scanning but are unable to do so, you may have relief by having the urine drained using a condom or bladder catheter. This would only be done at your request and for your comfort. If a bladder catheter is used, then your urine will be cultured to test for infection. At the end of the testing session, the vascular catheters will be removed, and after we have checked to make sure there has been no bleeding under the skin, you will urinate into a container in order for us to determine how much radioactivity already is in the urine.

After the PET scanning session, you will stay overnight in the Clinical Center for observation and to collect all your urine for 24 hours from the time of injection of the fluorodopamine.

ASSOCIATED TESTS

You may be asked to undergo one or more associated tests. These tests include: treatment with a drug; exercise, video game, or lower body negative pressure (LBNP); magnetic resonance imaging (MRI); direct measurement of sympathetic nerve activity; or a cardiac catheterization. These tests are described in detail below. The accompanying chart shows which of these tests are planned in your case. You may decide whether you wish to undergo the planned associated tests, and you can change your mind at any time. You may receive one of the following drugs, either during the PET scanning session or in testing done on a separate day.
Yohimbine You may receive yohimbine by vein (a quick injection followed by a slow infusion). This drug stimulates release of noradrenaline (norepinephrine) from sympathetic nerves. Yohimbine often causes trembling, goosebumps, and cool, clammy palms. We have infused yohimbine many times in other clinical protocols, without any permanent untoward effects. Some patients have reported emotional feelings, such as elation, anxiety, or depression, but most have noted nothing unusual. Yohimbine may increase your blood pressure temporarily. In the event of an extreme increase in blood pressure (which can occur in hypertensive patients), an antidote anti-hypertensive drug, clonidine, will be available for use. In the 7 years during which we have used yohimbine us a research drug, in studies involving about 100 subjects. only 1 patient has required the antidote. The infusion will be given during most or all of the PET scanning.

Trimethaphan Trimethaphan is a type of drug called a ganglion blocker. It interferes with transmission of sympathetic nerve impulses through way-stations between the brain and the rest of the body. Trimethaphan can cause a dry mouth, dizziness and low blood pressure during standing, and decreased urinary and bowel movements. The drug is rapidly inactivated and must be given continuously by intravenous infusion. Its effects wear off very rapidly after the infusion is stopped. You will receive trimethaphan at a dose that produces characteristic effects on blood pressure and pulse rate responses during simple maneuvers such as blowing against a resistance for a few seconds. The infusion will be given during most or all of the PET scanning. We have infused trimethaphan many times in other clinical protocols, without any serious side effects. Your blood pressure is likely to fall slightly; if it falls excessively, the infusion rate will be adjusted, or the infusion may be stopped. The investigator will have available an appropriate antidote vasoconstrictor drug; however, we have never had to use it. You will not receive trimethaphan if you have a particular kind of glaucoma, an eye disease.

Nitroprusside Nitroprusside is a type of drug called a vasodilator. Nitroprusside relaxes blood vessels, causing blood pressure to fall. The fall in blood pressure activates the sympathetic nervous system reflexively, and the sympathetic activation tends to restore the blood pressure. Nitroprusside is therefore used to test the ability of the sympathetic nervous system to react appropriately. Nitroprusside is a powerful drug that works very rapidly. The drug is given i.v., and after stopping a nitroprusside infusion, the effects of the drug disappear rapidly. If you receive Nitroprusside, the drug will be given at a carefully controlled rate i.v. using a programmed infusion pump. Your blood pressure will be monitored closely and continuously by an investigator. The infusion rate will be adjusted so that your blood pressure decreases by 5-10 millimeters of mercury (about 5-10%). During the infusion, you should note nothing special. If the blood pressure begins to fall beyond the criterion amount, the infusion rate will be adjusted, or the infusion may be stopped. The investigator will have available an appropriate antidote vasoconstrictor drug; however, we have never had to use it. We have infused nitroprusside many times in other clinical protocols, without any untoward effects. The infusion will be given during most or all of the PET scanning.

Desipramine You may receive i.v. or orally a drug called desipramine, before the PET scanning. Desipramine is used commonly in psychiatry to treat depression; to produce an anti-depressant effect, however, the drug must be given many times over about two weeks. The effects of one or two doses of desipramine are remarkably few--perhaps fatigue or dry mouth. Other side effects can include dizziness or a fast pulse rate when standing. We are including desipramine because it interferes with uptake of fluorodopamine into sympathetic nerve endings, and interference with the picture of the heart in subjects pretreated with desipramine would demonstrate that the picture does in fact portray the sympathetic nerves. We have administered desipramine many times in other clinical protocols, without any untoward effects.

Methylprednisolone Methylprednisolone acetate is a "steroid.. There are many metabolic effects of steroids. We are using this drug to inhibit the uptake of positron-emitting fluorodopamine by cells that are not nerves. Although chronic administration of this type of drug produces many medical and psychiatric effects, a single injection should be safe.

Tyramine Tyramine is a chemical found in some foodstuffs such as hard cheese and wine. When given as a drug, tyramine releases norepinephrine, the chemical messenger of the sympathetic nervous system. Tyramine produces no direct effects, but because of the norepinephrine release, tyramine usually increases blood pressure. The drug works rapidly, so that it is given by i.v. infusion, and the effects of the drug disappear soon after the infusion ends. You will receive tyramine to increase your blood pressure by 10-20 millimeters of mercury. This amount of increase in blood pressure corresponds to that occurring during mild exercise. The infusion will be given during most or all of the PET scanning. Tyramine has been used in diagnostic testing for conditions such as autonomic failure and pheochromocytoma, in order to assess the presence of releasable stores of norepinephrine. If you have a pheochromocytoma, you will not receive tyramine, because the drug can stimulate the tumor and produce dangerously high blood pressure. Tyramine also is contraindicated in patients receiving treatment with some types of anti-depressant medication.

Sedative In patients with some forms of heart disorders, sedatives are often prescribed. Although it is likely that sedation affects the function of the sympathetic nerves in the heart, this issue has never been addressed directly in people. You may receive a sedative drug, such as alprazolam, orally before the PET scanning; or you may receive the rapidly-acting sedative, diazepam, i.v. If you are given a sedative, appropriate monitoring of your pulse rate, blood pressure, and breathing will be done. We have used alprazolam or diazepam in previous protocols, without any adverse effects.

Perfusion Imaging Agent Drugs that can be used to measure blood flow to the heart are called perfusion imaging agents. During the PET scanning session, you may receive one or more injections of a positron-emitting perfusion imaging agent called [13N]-ammonia. The dose of active drug is vanishingly small, and so you should feel nothing unusual due to administration of the perfusion imaging agent.

Tritiated Norepinephrine Norepinephrine that has a trace amount of radioactivity in the form of tritium (tritiated norepinephrine) may be given i.v. Although norepinephrine is a powerful drug, the dose you will receive will be too small to produce any noticeable effects. Radiation doses to all organs are also very small, as explained below.

As part of the testing, you may exercise using a special type of bicycle-like device while you are lying down, or you may play a video game. Both these manipulations produce increases in blood pressure and pulse rate, stimulating the sympathetic nervous system.

Another means to stimulate the sympathetic nervous system is LBNP. In this procedure, the legs and pelvic area are enclosed in an air-tight barrel-shaped chamber, and air is sucked out of the chamber, producing negative pressure. Blood pools in the legs, producing "artificial gravity". As during normal standing, the sympathetic nervous system is activated during LBNP. You may undergo LBNP at a mild intensity (15-25 millimeters of mercury of suction) during the PET scanning or in testing on a separate day.

We have used exercise, video games' or LBNP in several other clinical protocols, without any serious or long-lasting adverse effects.

MRI is a non-invasive method to visualize the heart walls and chamber; MRI does not involve radioactivity or any proven health risk. Because of the strong electromagnetic field, you may not be allowed to undergo MRI if you have metal in your body. A procedure called microneurography can be used to measure sympathetic activity directly via thin metal needles placed near the side of the knee. This procedure will be done only with your separate consent. The procedure is discussed in detail in a separate consent form. A lumbar puncture may be done in order to obtain spinal fluid for assays. You lie on your side, curled up with your knees at your chest (The procedure can also be done with you sitting leaning forward). Your lower back is washed and a local anesthetic injected with a needle into the skin to make it numb. This may sting for a few seconds. A needle will be inserted through the numbed skin and into the space between the bones in your back. You may feel a sensation of pressure. About two tablespoons of cerebrospinal fluid (CSF) will be removed. The time it takes to collect the CSF may vary, but generally is 5 to 20 minutes. The needle is then removed, and you may get up and move around when your doctor says you may. Your doctors may have recommended that you undergo a cardiac catheterization ._. evaluation of a heart disease. You should understand that in this protocol, although cardiac catheterization may be indicated for clinical reasons, there is also a research aspect that is being done to broaden our understanding of mechanisms of heart disease. The results of this research may benefit you directly, by providing information about the function of nerves supplying your heart and about the function of your heart muscle. This information could be relevant to your diagnosis (the cause of the problem), disease mechanisms, prognosis (long-term outlook), or treatment. Cardiac catheterization has been performed at the NIH or at other centers as part of research studies involving your condition.

If cardiac catheterization is already planned in your case in order to evaluate a heart disease, the research aspect of the cardiac catheterization involves about one hour extra in catheterization laboratory. The cardiac catheterization will be done in a special catheterization suite by a cardiologist with extensive experience in this procedure. Before the catheterization. you will be admitted to a cardiology ward, and you will be transported to the catheterization suite. After cleansing and numbing of the skin, a plastic catheter will be inserted into a vein in the arm or thigh. The catheter will be long enough that it can be threaded up the vein into the heart. The placement of the catheter will be verified by fluoroscopy, a type of real-time X-ray. Another catheter will be placed into an artery, by a procedure similar to that described above for he PET scanning.

During the cardiac catheterization, we will be measuring the rate of release of norepinephrine in the heart, by infusing a tiny amount of radioactive, tracer-labeled norepinephrine ([3H]-l-norepinephrine) and drawing blood samples from the vein draining your heart by way of a specially placed catheter. You will not notice anything unusual due to the infusion. It is possible that another i.Y. Will be placed, into which the tracer-labeled norepinephrine will be given.

During the infusion of tracer-labeled norepinephrine, you may receive one of the drugs described above, such as yohimbine, or you may play a video game. The infusion of the tracer labeled norepinephrine will last 20-60 minutes, depending on whether you undergo these other manipulations.

You may be asked to undergo re-testing under this protocol, such as after treatment with a drug. This would be done only with your additional consent at that time.

RISKS AND OTHER SAFETY ISSUES

There are several potential sources of risk in this study: the use of radioactivity, the arterial catheter, the various drugs, the exercise or physiological "stress" tests, the MRI imaging, and cardiac catheterization. The radiation doses you will receive as a result of participating in this study include radiation from the administration of positron-emitting fluorodopamine. If you are undergoing PET scanning of the chest, then you will receive l mCi of positron-emitting fluorodopamine. If you are undergoing PET scanning of limbs, then you will receive 4 mCi of positron-emitting fluorodopamine. Using the standard way of describing radiation dose, for these scans, if you receive l millicurie of positron-emitting fluorodopamine, then you will receive about 0.82 rem to the wall of the urinary bladder, 0.71 rem to the kidneys, 0.14 rem to the spleen, and lower doses to all other body organs. If you receive 4 millicuries of positron-emitting fluorodopamine, then you will receive about 3.28 rems to the wall of the urinary bladder, 2.84 rems to the kidneys, 0.56 rem to the spleen, and lower doses to all other body organs. The half-life of fluorodopamine is short. This means that the length of time you will be exposed to radiation will be small. By the next day, there will be essentially no radioactivity in your body. In fact. by the end of the testing session, we expect that over 50% of the injected radioactivity already will be in the urine. This is why by far the highest radiation dose would be from the radioactive urine to the wall of the bladder and to the kidneys. The actual value for the radiation dose to the wall of the urinary bladder will depend on how frequently you urinate after the PET scanning.

In addition to radiation exposure from positron-emitting fluorodopamine ([18F]-6F-DA), and radiation exposure from germanium-gallium (68Ge-68Ga, used for the preliminary transmission scanning before [18F]-6F-DA and before the perfusion imaging agent), you may undergo radiation exposure from tritiated norepinephrine ([3H]-l-NE, up to 100 microCuries), from the perfusion imaging agent. positron-emitting ammonia ([13N]-ammonia, [13N] NH3, 20 milliCuries of [13N]-ammonia per injection), or from fluoroscopy, which is used during cardiac catheterization to determine the positioning of the catheters. The following charts show the estimated radiation doses. The doses circled in the charts refer to the estimates in your case.

For PET scanning of the chest:

[18F]-6F-DA 68Ge-68Ga[13N] NH3[3H]-l-NEFluoroscopy
Highest doseBladder 0.8 Heart 0.1 Bladder 0.2Bladder 0.0Lungs 0.2
2d Highest Kidneys 0.7Lungs 0.1Kidneys 0.1Kidneys 0.0Heart 0.1
3d Highest Spleen 0.1 Breast 0.1 Brain 0.1Spleen 0.0 Breast 0.0

For PET scanning of limbs:

[18F]-6F-DA 68Ge-68Ga[13N] NH3[3H]-l-NEFluoroscopy
Highest doseBladder 3.3 Heart 0.1 Bladder 0.6Bladder 0.0Lungs 0.2
2d Highest Kidneys 2.9Lungs 0.1Kidneys 0.3 Kidneys 0.0Heart 0.1
3d Highest Spleen 0.6 Breast 0.1 Brain 0.3Spleen 0.0 Breast 0.0

Please be aware that this radiation exposure is necessary for this research study only and is not essential for your medical care. The NIH Radiation Safety Committee and the NIH Radioactive Drug Research Committee have reviewed the use of radiation in this study and approved this use as being necessary to obtain the research information desired. For your reference, NIH Radiation Safety guidelines limit radiation exposure to 3 rems to any organ within a 13-week period and 5 rems annually; FDA regulatory limits are 5 rems per single administration and 15 rems per year to the above-listed organs.

The potential long-term risks from these radiation doses are uncertain, but these doses have never been associated with any definite adverse effects. Thus, the risk to you, if any, is estimated to be very slight.

The radiopharmaceuticals that you will receive are being administered under an Investigational New Drug (IND) approval from the Food and Drug Administration (FDA), with W. Eckelman, Ph.D., as the sponsor; both the sponsor and the FDA have access to the medical records of research subjects.

Please advise us if you have participated in research studies that involved use of radiation so that we can ensure that the total radiation dose from all studies is not excessive. Examples of such studies include x-ray studies in radiology departments, cardiac catheterization, fluoroscopy, and nuclear medicine studies (e.g., technetium and PET scans).

The risks of the arterial catheter include bleeding, pain, clotting, and infection. No serious or long-lasting complications have occurred in over 150 arterial catheterizations we have done since 1980. In particular, because of the use of the local anesthetic, you should feel little if any pain during the catheter insertion. The procedures we use to prevent these complications are discussed above. It is possible that you may develop a temporary black-and-blue mark or swelling at the site of the catheter. The possible side effects of the drugs are described above for each drug. All the drugs have been used in various clinical or preclinical studies over the past several years, without any serious or long-lasting complications. If you have an arterial catheter in place, your blood pressure and electrocardiogram will be monitored continuously during the PET scanning. If we notice any problem that we think could be related to the procedure or drug, then the manipulation or infusion will be stopped. The risks of bicycle exercise and playing a video game should be small; however, in patients with coronary heart disease, these stressors may evoke angina (chest pain or pressure) or abnormal heart rhythms, just as during a treadmill stress test. If this happens, the exercise or video game will be stopped, and you may receive standard medical treatments as indicated clinically.

LBNP produces "artificial gravity". The amount of LBNP you will receive would correspond to less than the gravitational force you would undergo by simply standing up. LBNP should therefore be safe. One patient fainted during LBNP. The patient regained consciousness rapidly after LBNP was stopped. If you have a history of fainting, you may be at increased for fainting during LBNP. Your blood pressure will be monitored continuously, and if you have signs or symptoms suggesting that you may faint, LBNP will be stopped.

Studies show that 30-40 % of patients develop a headache within the first few days after a lumbar puncture. Usually they are not severe and improve without treatment other than a mild pain reliever. Prolonged headaches, those lasting longer than 7 days, develop in only 0.5 to 2 percent of people, (about one in 50 to 200 patients). These prolonged headaches usually taper off within 2 weeks of the lumbar puncture. In rare cases, headaches have persisted for months or years.

Headaches after lumbar punctures are due to the reduced amount of CSF. In most people, the CSF which is removed is rapidly replaced by the body. Prolonged headaches are thought to result from a persistent leakage of CSF from the area of the lumbar puncture. If your headache is prolonged, you and your doctor may decide to perform a "blood patch." A blood patch requires removing blood with a needle from a vein in your arm and then injecting it into the area of your back where the lumbar puncture was performed. This is done to seal the leak of CSF. Other rare complications of lumbar puncture include temporary double vision and infection.

There are may potential risks of cardiac catheterization, include clotting, bleeding, infection, abnormal heart rhythms, and even knotting of the plastic tubes in the blood vessels. The research portion of the cardiac catheterizations in this study involves only a "right heart" catheterization-that is, a tube is advanced via a vein into a heart chamber that is not the main pumping chamber. It is important for you to realize that over the past two decades, we have conducted several hundred right heart catheterizations in patients with a variety of heart diseases; no patient has experienced any of these complications due to right heart catheterization. Several blood samples will be drawn through the arterial catheter before and after the injection of fluorodopamine or during the associated testing. The total amount of blood to be drawn during any PET testing session will be less than 100 ml, and the total amount of blood to be drawn for your participation in the entire protocol, including the associated tests, will be less than 225 ml, about half of what you would normally donate when giving blood. Current NIH guidelines allow about twice this amount to be drawn from research subjects in any 6-week period. This amount of blood drawing will not affect you.

As in all NIH clinical protocols, you may end your participation at any time, for any season.

Summary of Procedures

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OTHER PERTINENT INFORMATION

  1. Confidentiality. When results of a study such as this are reported in medical journals or at meetings, the identification of those taking part is withheld. Medical records of Clinical Center patients are maintained according to current legal requirements, and are made available for review, as required by the Food and Drug Administration or other authorized users, only under the guidelines established by the Federal Privacy Act.
  2. Policy Regarding Research-Related Injuries. The Clinical Center Win provide short-term medical care for any physical injury resulting from your participation in research here. Neigher the Clinical Center nor the Federal government will provide long-term medical care or financial compensation for such injuries, except as may be provided through whatever remedies are normally available under law.
  3. Payments. If you are a patient, you are not paid for taking part in NIH studies. Exceptions for volunteers will be guided by Clinical Center policies.
  4. Problems or Questions. Should any problem or question arise with regard to this study, with regard to your rights as a participant in clinical research, or with regard to any research-related injury, you should contact the principal investigator, Dr. David Goldstein or these other staff members also involved in this study.
    Building 10, Room 6N252
    Telephone (301) 496-2103
    National Institutes of Health
    Bethesda, Maryland 20205
  5. Consent Document. It is suggested that you retain a copy of this document for your later reference and personal records.

COMPLETE APPROPRIATE ITEM BELOW, A or B:

A. Adult Patient's Consent.

I have read the explanation about this study and have been given the opportunity to discuss it and to ask questions. I hereby consent to take part in this study.
Signature of Adult Patient & Date Signed
Signature of Investigator & Date Signed

B. Parent's Permission for Minor Patient.

I have read the explanation about this study and have been given the opportunity to discuss it and to ask questions. I hereby give permission for my child to take part in this study. (Attach NIH 2514-2, Minor's Assent, if applicable.)
Signature of Parent(s) & Date Signed
(If otherthan parent specify relationship)
Signature d Witness & Date Signed