Consent Form for Participation in Research

New York Medical College

 

                                                                        Name of Patient/Subject :

Affiliate:

                                                                        Address:

 

                                                                        Chart Number:

 

Title of Research Project:   Circulatory Dysfunction in the Chronic Fatigue Syndrome

          

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Note: 

This project does not involve the experimental use of a new drug/device/procedure.

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Explanation of Research Project:


Purpose of the Study

You are being asked to participate in research to determine whether the regulation of blood pressure and blood flow cause the symptoms of chronic fatigue syndrome (CFS) and whether treatment of abnormal blood pressure and blood flow improves these symptoms. Evidence suggests that patients with CFS can have symptoms along with abnormal blood flow when they are kept upright. Adolescents, in particular, develop high heart rates often associated with low blood pressure along with symptoms such as light-headedness, mental confusion, sweats and palpitations. Our research suggest that this is due to alterations in the function of blood vessels particularly causing fluid to be trapped or “pooled” in the lower parts of the body. This can sometimes show up as swelling when blood is trapped in muscle or purple discoloration or mottling of the legs when blood is trapped in the skin. Pooling leads to decreased blood returning to the heart thus being unavailable to be pumped. This in turn stresses the autonomic nervous system (ANS), which is the part of the nervous system that tries to keep blood pressure normal.

The purpose of the study is to determine the mechanism for malfunction of the blood vessels and to learn whether improvement in blood vessel function with medication can improve pooling and also the ANS.

 

Participation

If you decide to participate we will compare clinical information obtained from patients with CFS to information from healthy volunteers. During screening, we will ask questions to determine whether you have CFS. A physical examination will be performed to look for heart disease and neurologic disease. We will also ask you to fill out a questionnaire which relates to symptoms of the syndrome, to fainting problems, and to your general state of health. Laboratory blood tests may have been performed to rule out thyroid disease, liver disease and anemia. If you are a woman and are willing to participate, we will also need you to obtain a test to ensure that you are not pregnant.

 

All subjects - CFS and healthy volunteers - will undergo accepted tests of the ANS

These are performed in a laboratory with an intravenous catheter in place while being continuously monitored for blood pressure, respiratory rate and heart rate:

1) tests of “heart rate and blood pressure variability” at rest and while upright. This test measures changes in the way heart rate and blood pressure are regulated by recording heart beat and blood pressure for a period of time and analyzing those recordings.

2) determination of the blood pressure and heart rate response to the quantitative Valsalva maneuver. This maneuver is performed by blowing against a pressure for approximately 10 seconds.

3) determination of blood pressure and heart rate responses to rhythmic deep breathing in time to a metronome.

4) head-up tilt table testing, a routine test which is used to evaluate patients with CFS or fainting.

Patients are placed on an electrically driven table with supporting footboard capable of tilting upright. Patients are tilted upright in steps from flat to 20o, 35o, and 70o. During the 20o and 35o tilts we will make measurements of blood flow (see below) and take small blood samples for hormone levels.

 

All patients will also undergo tests of how the blood vessels function:

1) strain gauge venous plethysmography which measures leg and arm vein filling using a strain gauge (an elastic band) encircling the limb and detects changes in fluid within the limb caused by rapidly inflating a blood pressure cuff. Plethysmography will be performed in the arm and the leg while lying flat, and during the tilt tests.

2) impedance plethysmography which uses pairs of electrocardiogram stickers to measure small

changes in voltage on passing a tiny current (similar to an electrocardiogram). The voltages tell us

whether blood volume is increasing or decreasing and also information about blood flow.

3) transcranial Doppler ultrasound which uses sound waves to measure the amount of blood flow to the brain. The sensor will be placed at the left temple of the head.

4) cardiogreen dye dilution which is a technique to measure the total body blood volume and blood flow by introducing a small amount of dye into a vein and measuring the amount of color change through a noninvasive finger sensor.

5) laser-Doppler flowmetry will be used to measure skin blood flow while lying flat and during tilt tests. While flat we will also be able to tell how well nerves are working by administering tiny amounts of medication to a small area of skin while continuing to measure flow. There are no affects to your system from these medications.

 

Treatment of CFS Patients

CFS patients only will receive a test of treatment over two 2 week periods with one week in between (a total of 5 weeks) . All CFS patients will receive a single oral treatment of proamatine (midodrine), a medication which contracts blood vessels and is used to treat patients with low blood pressure and lightheadedness. Patients will also receive placebo which is a substance with no medicinal value. Patients will be assigned to take proamatine or placebo in random order (by the flip of a coin) and neither the patient nor the doctors will know which is which - this is called double-blind testing. The pharmacy will know. After initial testing, patients will receive the first medication for 2 weeks and then be retested with questionnaires, blood vessel function test and low angle 35o tilt testing. All treatments will stop (called a “washout period”) for 5 days. Patients will start the second medication and testing repeated after another 2 weeks.

 

Test sessions will last approximately 3 hours.

 

Risks and discomforts

Monitoring, plethysmography, laser-Doppler flowmetry and transcranial Doppler ultrasound are painless and contribute no additional risk to your care. There is no foreseeable risk to performing the Valsalva maneuver or rhythmic breathing. The dye will be administered intravenously. It is chemically neutral and has no direct effects to your system. Should there be any sign of an allergic response such as rash, wheezing, or a decrease in blood pressure, administration of the dye will stop and counter measures taken.

Tilt testing is intended to replicate fainting or pre-fainting symptoms which constitute its primary risk. Tilt testing is, however, the standard for assessing patients with unexplained fainting and also has become standard in the assessment of patients with CFS. Low angle tilts to 20o, and 35o have been well tolerated by a pilot group of CFS patients and healthy volunteers. Physical risks will be minimized by returning patients who faint or nearly faint promptly to the back-down position. Intravenous fluids can be given if needed at the end of the tilt test and invariably improve overall well-being after fainting. In recent testing neither CFS patients nor volunteers have actually fainted.

Blood drawing risks (during screening laboratory evaluations) include pain from the needle stick and bruising.

Proamatine is a medication which contracts blood vessels and therefore can cause high blood pressure in sufficiently large doses. This is uncommon in CFS patients whom we have treated. Blood pressure will be home monitored with medication change throughout the treatment phase and the medication adjusted or stopped as necessary. Other side effects such as itchy feelings, or a pins and needles sensation are usually short-lived or may call for a decrease in dose if persistent. Worsening CFS symptoms could occur as well. We will monitor patients for these possibilities over the course of the study and alter medication if necessary.

 

Benefits

There may be direct benefit from this study to patients with blood vessel function and associated

abnormalities of the ANS especially if proamatine improves their function. You may therefore derive immediate benefit from the study because it may directly improve your health. Also the study will enable us to detect changes in blood vessel function which may furnish data important for determining other suitable medical therapy in CFS patients. There is no direct benefit to healthy volunteers, although their contribution is essential for purposes of experimental control. Healthy patients will contribute to general medical knowledge.

 

Alternatives to participation

The alternative is standard  medical care.

 

Payments and compensation

$200 per subject.

 

Additional information

There will be no additional cost for testing or medication to the patients. Significant new findings which may relate to your willingness to continue participation will be provided. Any deleterious change in clinical status detected during monitoring and testing will be promptly treated using standard therapeutic regimens. Over a four year period we expect to enroll 50 patients with CFS, and 30 healthy volunteers.

 

All inquiries will be promptly answered by contacting either of the investigators Julian M. Stewart M.D., Ph.D. (914-594-4370)

                                                                                                                                                                                                                                   


Consent Form for Participation in Research (continued)

 

Financial Compensation

New York Medical College and its affiliated institutions (Metropolitan Hospital Center, St. Agnes Hospital, and Westchester Medical Center) do not provide financial compensation for injury or illness resulting from participation in research.  Essential medical care for any injury or illness from participation is available.  The investigator should be contacted in the event of a research-related injury.  Unless the sponsor provides otherwise, payment for medical treatment, both standard and experimental, as well as treatment of any side effects will be assumed in the usual manner by you personally or through your medical insurance.

 

Confidentiality

This consent form and other medical records relating to this study may be subject to review by representatives of the sponsor and the Food and Drug Administration.  Unless explicitly stated otherwise in this form, your name will not be revealed except when required by state or federal law.  If this investigation is published, you will not be identified by any personal data.  You will be given a copy of the signed consent form.  Other copies will be kept in confidential files in the investigator?s office and (if appropriate) with your medical chart and may be reviewed by the College?s Office of Research Administration.

 

Voluntary participation -- Offer to answer questions

Your signature indicates that you understand this consent form and freely consent to participate in this study.  You are free to refuse or to discontinue participation in the study at any time without penalty or loss of benefits to which you are otherwise entitled.  You may call the Office of Research Administration at (914) 594-4480 if you have questions about your rights as a research subject.  The investigator will answer any questions you have about your participation in the study.

 
 

                                                            Not Valid Without the

                                                            Committee Stamp                                                                                                                                             

 

                                                                                                                                                           

                                                                        Subject’s Signature (7 years old and above )                  

 

                                                                        Date                

                                                                       

                                                                                                                                                           

Signature of person authorized to consent for subject or witness if consentor is illiterate or unable to sign

                                                                       

                                                                                                                                                                                                                        Signature of person obtaining consent                            

 

                                                                        Date                

 

Void One Year From Above Date                      Julian M. Stewart MD, PhD              914-594-4370

Sponsor: American Heart Association                 Name of Principal Investigator               Telephone

                                   

The Committee for Protection of Human Subjects is the Institutional Review Board for: New York Medical College  Metropolitan Hospital Center   St. Agnes Hospital              Westchester  Medical Center

 

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