RESEARCH suBject
Informed Consent Form
Protocol Title: Will testosterone with or without growth hormone improve
bone structure?
Principal Investigator: Peter J. Snyder
778 Clinical
Research Building
215-898-0208
Emergency Contact: Endocrinology Fellow on
Call
215-662-2300
Why am I being asked to volunteer?
You are being
invited to participate in a research study to test whether testosterone and
growth hormone improve bone structure more than testosterone alone. You are
being asked to volunteer because you have been diagnosed with a pituitary or
hypothalamic disease that may cause deficiency of testosterone and growth
hormone. Your participation is voluntary, which means you can choose whether
or not you want to participate. If you choose not to participate, there will
be no loss of benefits to which you are otherwise entitled. Before you can
make your decision, you will need to know what the study is about, the
possible risks and benefits of being in this study, and what you will have to
do in this study. The research team is going to talk to you about the
research study, and they will give you this consent form to read. You may
also decide to discuss it with your family, friends, or family doctor. You
may find some of the medical language difficult to understand. Please ask Dr.
Snyder or the research team about this form. If you decide to participate,
you will be asked to sign this form.
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What is the purpose
of this research study?
The purpose of this study is to determine if testosterone,
which is the principal male hormone, and growth hormone improve bone structure
and therefore improve the strength of bone and reduce the likelihood of bone
fractures. The method of assessing bone structure is magnetic resonance imaging
(MRI). Until now there has been no way of determining bone structure except by
taking a bone biopsy, a process that is moderately painful. We have developed a
new way of determining bone structure that involves magnetic resonance imaging
instead of a biopsy. The effects of testosterone and growth hormone will be
determined by comparing bone structure before and after treatment. The
treatment will be testosterone for all the men in the study and growth hormone
for half of the men.
How long will I be
in the study? How many other people will be in the study?
The study will last two years. A total of 40 subjects will
take part in the study, all at the
What am I being
asked to do?
The study requires twelve visits, including two screening
visits and ten return visits. Five 24-hour urine collections will be required.
Collections involve collecting all of the urine you produce over a 24-hour
period. You will be provided with written instructions for urine collection and
storage. Blood sampling will be required at each visit. You will apply a
testosterone gel (Androgel, Solvay Pharmaceuticals) daily beginning after the
second screening visit. The testosterone gel comes in a tin-foil packet. To
apply the gel, you tear open the packet, squeeze the gel out onto your palm,
and spread it over your abdomen, upper arms, or thighs. You then wait a couple
of minutes for the gel to dry before getting dressed. You may or may not be
chosen randomly to receive growth hormone (Humatrope, Eli Lilly). If you are
chosen to receive growth hormone, you will self-inject growth hormone once a
day during the two-year treatment period. If you ingest less than 1000 mg of
calcium a day in your diet, determined through a questionnaire that reviews
your diet history, you will be asked to take a calcium and vitamin D pill.
Procedures and Tests:
Screening:
During the first screening visit, you will review and
sign the consent form, provide a medical history including calcium intake,
undergo a general physical examination, including a digital rectal examination
(an examination of the prostate which involves introducing a gloved finger
through the rectum, to detect irregularities of the prostate); routine blood
chemistries, blood count, testosterone, estradiol, SHBG (a protein from which
we can calculate the amount of free testosterone),IGF-1 (a measure of growth
hormone production), hemoglobin A1c (a test for sugar diabetes), and PSA
(screening test for cancer of the prostate). The American Urological
Association (AUA) symptoms score questionnaire and a sleep questionnaire
(Epworth sleepiness score) will be completed.
Time of visit: 1 hour. Amount of blood: two tablespoons.
If the serum IGF-1 concentration is not less than normal,
you will be asked to have a test of growth hormone secretion on another
morning. For this test, you will have a small needle placed in a vein in your
arm from which blood will be drawn and the test medications administered. One
test medication is arginine, which will be given by intravenous infusion during
a course of 30 minutes. At the end of this infusion, a dose of growth
hormone-releasing hormone will be given intravenously in 30 seconds. You could
experience a sensation of warmth for several seconds after the growth hormone
releasing hormone injection. Blood will be drawn just before the arginine
infusion, at the end of the arginine infusion, and 30, 60, 90 and 120 minutes
after the growth hormone releasing hormone dose.
Time of visit: 2 1/2 hours. Amount of blood: 3 tablespoons
During the second
screening visit, we will ask you to have blood drawn to measure
testosterone, estradiol, SHBG, and markers of bone metabolism and will ask you
to bring a 24 hour urine collection for a test of bone metabolism. You will be
asked to have a bone density test (DEXA scan) of the spine and hip, peripheral
quantitative computed tomography (p-QCT) and an MRI of the tibia (bone in the
lower leg), during that visit. The DEXA scan is a test of bone thickness that
uses a small beam of radiation and will take approximately 20 minutes. The
p-QCT uses a low energy x-ray beam to measure the density of bones of the arm
and of the lower leg. It measures the hard outer layer of bone (cortical bone)
separately from the inner layer of bone (trabecular or “spongy”
bone). The scan takes (about 15 minutes).
The
MRI will take about 30 minutes. MRI is an approved, non-invasive test, which is
now used extensively in patient evaluations to visualize tissues throughout the
whole body. Several sets of images will be acquired from your tibia (bone in
the lower leg) for the purpose of gaining information about the strength of
your bones.
Time of visit: Three hours. Amount of blood: two tablespoons.
Treatment:
Month 0
During this visit
you will also be instructed in the use of the testosterone gel and, if you have
been chosen to receive growth hormone, the self-administration of growth
hormone.
You will receive a
supply of testosterone gel (Androgel) and, if you have been chosen to receive
growth hormone, a supply of growth hormone (Humatrope). If your calcium intake,
as determined by a questionnaire, is less than 1000 mg per day, you will
receive Caltrate + D (a pill containing 600 mg of elemental calcium and 400
units Vitamin D). The initial dose of Androgel will be one packet of 5 g a day,
which is the typical starting dose. The initial dose of growth hormone will be
based on your weight (2 µg/kg of body weight).
Time of visit:
Thirty minutes.
Treatment: Month 1
A single blood sample will be taken to measure testosterone,
IGF-1, bone markers, and estradiol. You will be asked to bring a 24-hour urine
collection.
Time of visit: 20 minutes. Amount of blood drawn: Two tablespoons.
Month 2
A single blood sample will be collected to measure
testosterone.
Time of visit: 20 minutes. Amount of blood: One tablespoon.
If your average blood testosterone value at months one and
two is between 400 and 800 ng/dL (the normal levels for testosterone), you will
continue using the same dose of Androgel. If the average is below 400, the dose
will be increased to 7.5 g/day (one packet of 5g/day and one packet of 2.5
g/day). If the average is over 800, the dose will be decreased to 2.5 g/day
(one small packet). If the dose is changed, your blood testosterone will be
measured 1 and 2 months after the change.
If the serum testosterone concentration is below 400 while
using 7.5 g/d, the dose will be increased to 10 g/d (two 5 g packets applied at
the same time). Whenever the average of two testosterone values in a row is
outside the normal range, the dose will be changed as above.
Month 3
You must fast after midnight on the day before this visit.
You will receive a physical examination, including a digital rectal exam, have
a single blood draw for testosterone, glucose and Hemoglobin A1C, IGF-1, PSA,
blood concentration, and a test of bone metabolism, and fill out the AUA and
Epworth sleepiness score questionnaires.
Time of visit: 45 minutes. Amount of blood: two tablespoons.
Month 6
A single fasting blood sample will be taken to measure
testosterone, glucose, and IGF-1.
Time of visit: 20 minutes. Amount of blood: two tablespoons.
Month 9
You will have the same tests as in previous visit at month
6.
Month 12
You must fast after midnight on the day before this visit.
You will provide a medical history, receive a physical examination, including a
rectal exam, and have a single blood draw for testosterone, estradiol, SHBG,
IGF-1, bone markers, PSA, blood chemistries, blood count, and HgbA1c. You will
be asked to bring a 24-hour urine collection at the time of this visit. You
will be given the AUA, Epworth sleepiness score, and calcium questionnaires to
fill out. You will have a bone density test (DEXA scan) of the spine and hip,
peripheral-QCT (p-QCT) and an MRI of the tibia (bone in the lower leg).
Time of visit: 3 hours. Amount of blood drawn: Three tablespoons.
Month 15: You will have the same tests as in the 9-month
visit.
Month 18: You will have the same tests as in the 9-month
visit.
Month 21: You will have the same tests as in the 9-month
visit.
Month 24: You will have the same tests as in the 12-month
visit.
If the doses of testosterone and/or growth hormone need to
be changed more than specified above, it may be necessary for an additional
blood test to measure the serum testosterone and/or IGF-1 concentration to
determine the result of the change.
What are the
possible risks or discomforts?
Testosterone produced naturally and
that administered in the form of medications may contribute to prostate
diseases (including prostate enlargement and prostate cancer), increased red
blood cell count, breast enlargement, sleep apnea (breathing disorder during
sleep) and acne. You will be monitored for any indication of prostate cancer or
prostate enlargement at the time of your scheduled visits with questions
regarding your urinary function, by rectal examination of the prostate, and by
measuring the PSA (screening test for cancer of the prostate) in the blood. If
you develop prostate cancer or prostate enlargement that leads to severe
interference with urination during the course of this study, we shall ask you
to discontinue using the gel. If you develop a high red blood cell count, we
shall ask you decrease the amount of gel that you apply. If the red cell count
is still high, we shall ask you to discontinue using the gel. You will be
monitored for any indication of sleep apnea at the time of your scheduled
visits with a questionnaire. If you show symptoms of sleep apnea, you will be
referred to a sleep center for evaluation and treatment.
There may be some
discomfort at the site of needle insertion for blood sampling, and there is a
small risk of bruising, infection, inflammation at the site of the needle
insertion site, and fainting. Irritation or itching may occur at the
application site of gel.
Growth hormone may cause joint pain,
headaches, swelling of hands and /or feet, carpal tunnel syndrome, increased
growth of moles, the development of breast tissue, and diabetes. The initial
dose will be low (2 µg/kg body weight) and will be increased slowly (2
µg/kg/day a month), in order to minimize the chance of side effects. If a side
effect does occur, the dose will be decreased until the side effect goes away. Carpal tunnel syndrome will be assessed
by history of tingling in the fingers and by physical examination at 3, 12, and
24 months. Fasting serum glucose will be measured at 3, 12, and 24 months.
Values above 125 mg/dL will be repeated, and two values > 125 mg/dL will make
the diagnosis of diabetes mellitus. If you are diagnosed with diabetes, you
will be referred for further evaluation and treatment, but can remain in the
study if your hemoglobin A1c value is < 8.0%.
For the MRI test you will be lying on your back on a flat
surface, which will move you into the center of a large magnet, which is open
at both ends. Your head and most of your body will be inside the magnet. Only a
small amount of space remains between your body and the inside of the magnet. A
few individuals find the MRI equipment too restraining and cannot remain in the
machine long enough to complete the test or may be disturbed by the sounds of
the machine (which are loud and repetitive). Should you wish, you will be able
to discontinue the scan at any time.
The known risks associated with Magnetic Resonance Imaging
(MRI) are minimal. The procedure uses radio waves and a magnetic field to take
pictures. The greatest risk is a metallic object flying through the air toward
the magnet and hitting you. To reduce this risk, we require that all people
involved with the study remove all metal from their clothing and all metal
objects from their pockets. No metal objects are allowed in the magnet room at
any time. In addition, once you are in the magnet, the door to the room will be
closed so that no one inadvertently walks into the magnet room. The second
potential risk is that the magnet can cause any metallic object within the body
to move. Consequently, you should not have an MRI if you have any magnetic metallic
material in your eye, chest, abdomen, or brain, such as magnetic metallic clips
or a cardiac pacemaker.
For the MRI of the ankle, a detector coil has been developed
in order to obtain high quality images. This coil made of plastic and
copper is wrapped around the ankle. The coil is considered an
investigational device with no significant risk.
This research study involves exposure to radiation from the
DEXA and pQCT scans and therefore you will receive a radiation dose. This
radiation dose is not necessary for your medical care and will occur only as a
result of your participation in the study. At doses much higher than you will
receive, radiation is known to increase the risk of developing cancer after
many years. At the doses you will receive, it is very likely that you will see
no effects at all.
There
is also a chance of the occurrence of a side effect that is unknown at present.
What if new
information becomes available about the study?
During the course of this study, we may find more information
that could be important to you. This includes information that, once learned,
might cause you to change your mind about being in the study. We will notify
you as soon as possible if such information becomes available.
What are the
possible benefits of the study?
Testosterone treatment may improve your sense of well being, sexual
drive, bone thickness and muscle bulk. You might gain additional bone strength,
but this cannot be guaranteed. If you receive growth hormone, you would also
benefit from an additional increase in muscle mass and decrease in fat mass.
You will be participating in a study that might lead to a new way of studying
bone structure in men with low testosterone and growth hormone.
What other choices
do I have if I do not participate?
Your
participation in this research is voluntary. The alternative is to take
testosterone and/or growth hormone but not to have tests of bone. If you choose
not to participate in this program, this decision will not affect your medical
care. You also have the right to withdraw your participation at any time.
Will I be paid for being in this study?
You will be reimbursed
for transportation to the Hospital of the
Will I have to pay
for anything?
You
will not have to pay for the costs of the study procedures (i. e. blood and
urine tests, DEXA, MRI, p-QCT, and study examinations) or testosterone gel
(Androgel) or growth hormone (Humatrope) during your participation in this
program.
You and/or your health insurance may
be billed for the costs of medical care during this study if these expenses
would have happened even if you were not in the study, or if your insurance
agrees in advance to pay.
What happens if I
am injured or hurt during the study?
If you have a medical emergency during
the study you may contact Dr. Snyder or the Emergency contact listed on page
one of this form. You may also contact your own doctor, or seek treatment
outside of the
In the event of any physical injury resulting from research
procedures, medical treatment will be provided without cost to you, but
financial compensation is not otherwise available from the
When is the Study
over? Can I leave the Study before it ends?
This study is
expected to end after all participants have completed all visits, and all
information has been collected. This study may also be stopped at any time by
Dr. Snyder or the study Sponsor, the National Institute of Health, without your
consent because:
·
Dr. Snyder feels it is necessary for your health or
safety. Such an action would not require your consent, but you will be
informed if such a decision is made and the reason for this decision.
·
You have not followed study instructions.
·
The National Institute of Health (NIH) or Dr. Snyder
has decided to stop the study.
If you decide not
to participate, you are free to leave the study at anytime. Withdrawal will
not interfere with your future care.
Who can see or use my
information? How will my personal information be protected?
Your privacy and
the protection of your health information are important to us.
This section of the
consent will cover:
What
personal health information about you will be collected in this study?
Who
will use your information within the institution and why?
Who may
disclose your information and to whom?
Your
rights to access research information about you.
Your
right to withdraw your authorization for any future use of your personal health
information.
1. Personal health
information about you that will be collected in this study.
The following
personal health information will be collected, used for research and may be
disclosed or released during your involvement with this research study: Name,
address, telephone number, medical history, previous medical tests and
procedures, allergies, current and past medications or therapies, information
from a physical examination including blood pressure, heart rate, temperature,
height, weight, and information from the tests and procedures described earlier
in this document.
2. Why your
personal health information is being used.
Your personal
contact information is important for the
3. The personnel who may use or
disclose your personal health information
The following
individuals and organizations may use or disclose your personal health
information for this research project:
·
Dr. Snyder and his research staff
·
The
·
The
·
Authorized members of the
4. Who, outside of the
·
Authorized personnel from the National Institute of
Health (NIH) and its authorized agents
·
The study team will inform you if there are any
changes to the list above during your active participation in this study. Once
information is disclosed to others outside the
·
In all disclosures outside of the
5. How long will the
You authorization
for use of your personal health information for this specific study does not
expire. This information may be maintained in a research database. However,
the
6. Access to your records
During your
participation in this study, you will have access to your medical record and
any study information that is part of that record. Dr. Snyder is not required
to release to you research information that is not part of your medical record.
7. Changing your mind
You may withdraw
from the study for any reason simply by explaining this to Dr. Snyder. If you
decide not to participate, you are free to leave the study at any time.
Withdrawal will not interfere with your future care. If you decide to
withdraw, you will be asked to return all study related drug and equipment. If
you decide to withdraw, you may be asked to return for a close out visit.
You may also
withdraw your permission for the use and disclosure of any of your personal
information for research, but you must do so
in writing to Dr. Snyder at the address on the first page. Even if
you withdraw your permission, Dr. Snyder may still use your personal
information that was collected prior to your written request if that
information is necessary to the study. If you withdraw your permission to use
your personal health information that means you will also be withdrawn from the
research study. If you withdraw your permission to use any blood or tissue
obtained for the study, Dr. Snyder will ensure that these specimens are
destroyed or will ensure that all information that could identify you is
removed from these specimens.
Who can I call about my rights as a
research subject?
If you have questions regarding your
participation in this research study or if you have any questions about your
rights as a research subject don’t hesitate to speak with Dr. Snyder.
Concerning your rights as a research subject, you may also contact the Office
of Regulatory Affairs at the
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When you
sign this form, you are agreeing to take part in this research study. This
means that you have read the consent form, your questions have been answered,
and you have decided to volunteer. Your signature also means that you are
permitting the |
A copy of
this consent form will be given to you. You will also be given the
________________________
____________________________________
Name of Subject (Please Print) Signature of Subject Date
________________________ _____________________________________
Name of Person Obtaining Signature
Date
Consent (Please Print)