Clinical trial NCT03944577
Conditions: Heart Transplant
Keywords: coronary allograft vasculopathy lipid heart transplant low density lipoprotein proprotein convertase subtilisin/kexin type 9 PCSK9
Sponsor: University of Nebraska
Start date: 2019-07-15; Completion date: 2023-03-28
Enrollment: 26 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
Coronary allograft vasculopathy (CAV) is diffusely accelerated atherosclerosis of a transplanted heart. Evolocumab (Repatha) is an FDA-approved drug for lowering low density lipoprotein (LDL) in patients who have not received a heart transplant. This drug works as a PCSK9-inhibitor. The primary objective of this study is to measure the impact of PCSK9-inhibitors on serum LDL in heart transplant patients with CAV after 12 weeks compared to baseline.

Detailed description:
Heart transplant remains the treatment of choice for patients with advanced heart failure. Coronary allograft vasculopathy (CAV) is diffusely accelerated atherosclerosis of the donor heart, and limits long term survival after transplant. The pathophysiology of CAV is complex and involves smooth muscle proliferation, inflammatory infiltrates, and lipid deposition. To date, only statin therapy has reduced CAV-related mortality. PCSK9 inhibitors are a new lipid lowering therapy shown to reduce cardiovascular clinical events in patients with coronary artery disease. We hypothesize that PCSK9 inhibition via evolocumab will significantly lower low density lipoprotein (LDL) and be well-tolerated in transplant patients with CAV. This phase II, open label, single center trial with enroll up to 40 heart transplant patients with CAV for treatment with evolocumab for one year. The primary outcome will be percent change in LDL at 12 weeks. Secondary outcomes will include change in CAV progression, impact of evolocumab on immunosuppression regimens and transplant rejection, and change in serum lipids after 52 weeks. Results of this study are intended to provide safety data in heart transplant patients with CAV and assess secondary outcomes including CAV progression and impact on immunosuppression and transplant rejection.

Arms: arm 1: Patients who will receive the study drug.
Interventions: intervention 1: Evolocumab
Intervention descriptions: intervention 1: Enrolled study participants will be treated with evolocumab (Repatha) 140 mg injected subcutaneously every 2 weeks for 52 weeks. All study participants will receive instruction on correct self-administration by research pharmacists. Study drug will be mailed to patients on a monthly basis for self-administration by patients. The evolocumab dose (140 mg every 2 weeks) will remain constant for the duration of the study. Side effects will be assessed on a quarterly basis. Serious adverse events considered related to treatment, death, and pregnancy will all result in immediate discontinuation of the study drug.

Protocol documents:
Prot_SAP_000.pdf: 
 
ClinicalTrials.gov Cover Page 
 
 
 
Title: Impact of Evolocumab (Repatha) in Cardiac Transplant Patients with Coronary 
Allograft Vasculopathy (CAV) 
 
ID: NCT03944577 
 
Document date: 01.01.2022 
 
Document: Study Protocol and Statistical Analysis Plan 
 
 
 
 


Eligibility Criteria 
 
Inclusion criteria 
• Heart transplant patients 19-80 years of age 
• Coronary allograft vasculopathy documented by left heart cardiac catheterization 
• Able to provide signed informed consent 
 
Note: Evolocumab will be given as add-on therapy to heart transplant patients with 
CAV.  Patients already on statin or other lipid lowering therapy are eligible for 
enrollment. 
 
Exclusion criteria 
• Rejection requiring IV therapy in the prior 3 months 
• Infection requiring IV therapy in the prior 3 months 
• Active liver disease or hepatic dysfunction, defined as aspartate aminotransferase 
(AST) or alanine aminotransferase (ALT) > 3 times the upper limit of normal 
• Current or recent use of a PCSK9 inhibitor within the past 12 weeks 
• Dual organ transplant recipient other than heart/kidney 
• Renal dysfunction defined as GFR < 20 ml/min 
• Known allergy to evolocumab or its components 
 
 
Randomization/Registration Procedure 
 
Heart transplant patients will be recruited for participation solely from the University of 
Nebraska Heart Transplant clinic.  Our program provides care for approximately 330 
heart transplant patients in total, and currently performs 40-50 heart transplants per 
year.  Of these, over 40 patients already have a known diagnosis of CAV with more 
expected to be diagnosed in the coming year. 
 
Heart transplant patients with CAV will be identified by the primary investigator and the 
transplant cardiology team.  Eligible individuals will then be invited to participate (by 
phone call or during a clinical appointment) by the transplant cardiology research team.  
Interested patients will then be referred to trained personnel for informed consent, 
screening and study enrollment.  Coordination is expected between study enrollment 
and a standard post-transplant clinic appointment to facilitate participation. 
 
This study will be an open label, single cohort study.  No randomization of patients or 
treatment blinding will occur.  Enrollment is expected to take one year, with an 
additional one year of follow-up resulting in a total study duration of two years. 
 
 
 
 


Research Study Design 
 
Standard post-transplant care 
 
Heart transplant patients with CAV who primary transplant followup care at the 
University of Nebraska will serve as the study cohort.  Given the complexity of heart 
transplant patients, care is highly- protocolized and organized according to graft age.  
Care is most intensive in the first year following transplant wherein patients are initially 
evaluated on a weekly basis for the first month with reduced frequency (biweekly  
monthly  quarterly) based on clinical progress over the first year.  During year 2 post 
transplant, stable post-transplant patients are typically seen quarterly and this extends 
to biannual evaluations during year 3.  After 3 years, stable post-transplant patients can 
often be seen on an annual basis.  Thorough evaluations are completed annually 
including comprehensive labwork (complete blood count, complete metabolic panel, 
fasting lipid panel, thyroid function tests, hemoglobin A1c, creatinine kinase, urine 
protein analysis), assessment for donor specific antibodies, and imaging/testing.  
Imaging/testing includes an annual echocardiogram and chest x-ray as well as other 
imaging (DEXA scan, carotid and abdominal ultrasounds) at frequencies determined by 
comorbidities.  Immunosuppression is maintained with calcineurin inhibitors (primarily 
tacrolimus) and DNA synthesis inhibitors (mycophenolate mofetil, mycophenolic acid or 
azathioprine).  Patients are switched to mTOR inhibitors (primarily sirolimus) if 
significant renal dysfunction develops or CAV is diagnosed.  High dose steroids are 
started at the time of transplant and typically weaned off during the first year.  
Calcineurin inhibitors and mTOR inhibitors are dosed according to trough serum levels, 
and thus monitored at least every three months indefinitely. 
 
CAV is diagnosed by angiography.  Patients undergo a left heart cardiac catheterization 
annually for the first five years per standardized protocol.  Beyond five years, cardiac 
catheterization can be alternated with a dobutamine stress echocardiogram.  If the 
dobutamine stress test is abnormal (wall motion changes), a cardiac catheterization is 
completed to assess for CAV.  Once patients are diagnosed with CAV, annual cardiac 
catheterizations are completed.  Severity of CAV, once present, is based on 
angiographic findings as outlined in Table 3 below[1].  Of note, intravascular ultrasound 
can also identify CAV but is currently not used to guide management beyond changing 
immunosuppression regimen due to less outcome data (compared to cardiac 
catheterization). 
 
Transplant patients are closely monitored for graft rejection.  In general, rejection risk 
declines with increasing donor graft age.  Surveillance endomyocardial biopsies are 
completed during the first year post-transplant (selected patients can undergo serum 
gene expression testing in lieu of endomyocardial biopsy).  Donor specific antibodies 
are monitored on annually.  Beyond one year post-transplant, rejection is detected 
primarily by symptoms (new onset CHF symptoms, arrhythmias or increasing fatigue) or 
systolic dysfunction on echocardiogram which prompts an endomyocardial biopsy. 
 
 


Table 3 – ISHLT CAV nomenclature[1] 
Classification 
Severity 
Definition 
CAV-0 
Nonsignificant No detectable angiographic lesion 
CAV-1 
Mild 
Angiographic left main <50%   or 
Primary vessel lesion <70%     or 
Branch stenosis <70% 
CAV-2 
Moderate 
Angiographic left main <50%   or 
Primary vessel lesion ≥70%     or 
Isolated branch stenosis in 2 systems ≥70% 
CAV-3 
Severe 
Angiographic left main ≥50%   or 
≥2 primary vessels with lesion ≥70%     or 
Isolated branch stenosis in all 3 systems ≥70%    or 
Any CAV grade with EF ≤45% or restrictive physiology 
 
 
Research study design – patient enrollment and evolocumab administration 
 
Heart transplant patients with CAV will be eligible for enrollment per inclusion and 
exclusion criteria listed in Section 3.  The majority of heart transplant patient are on 
statin therapy (pravastatin is most common).  Evolocumab will be given either as add-on 
therapy for heart transplant patients with CAV currently prescribed statin or other LDL 
lowering therapy, as well as those unable to tolerate lipid-lowering medications. 
 
Study participation is expected to coordinate with the standard care of heart transplant 
patients.  As most patients with CAV are more than 2 years post-transplant, enrollment 
will likely occur around the patient’s annual clinical evaluation.  Female patients of 
childbearing potential will undergo pregnancy testing prior to or during the 
screening/enrollment visit before study drug administration.  Informed consent and 
baseline documentation will be completed by research personnel at the patient’s annual 
evaluation when feasible.   
 
Enrolled study participants will be treated with evolocumab (Repatha) 140 mg injected 
subcutaneously every 2 weeks for 52 weeks.  All study participants will receive 
instruction on correct self-administration by research pharmacists.  Study drug will be 
distributed to patients via courier or Fed Ex temperature-controlled coolers by the 
research pharmacy.  The evolocumab dose (140 mg every 2 weeks) will remain 
constant for the duration of the study.  Side effects will be assessed on a quarterly 
basis.  Serious adverse events considered related to treatment, death, and pregnancy 
will all result in immediate discontinuation of the study drug. 
 
Primary endpoint – LDL percentage change after 12 weeks of evolocumab therapy. 
 
The primary objective of this study is to measure the impact of PCSK9 inhibition via 
evolocumab on serum LDL in heart transplant patients with CAV after 12 weeks.  
Similar to prior phase 2 trials investigating evolocumab, LDL change will serve as the 
primary endpoint providing a direct benchmark for comparison of heart transplant 


patients.  Baseline LDL will be obtained at study enrollment, likely with the patient’s 
annual clinical evaluation.  After 12 weeks of therapy, a fasting serum lipid profile will be 
obtained for measurement of LDL and assessment of the primary endpoint.  Statistical 
analysis is detailed in Section 8 below. 
 
Secondary endpoints 
 
Assess the effect of evolocumab on CAV progression.  All patients enrolled will have 
CAV documented by cardiac angiography.  Standard post-transplant care includes 
annual angiograms in patients diagnosed with CAV to monitor for disease progression.  
CAV progression will be defined as an increase of one CAV grade (CAV-1  CAV-2 or 
CAV-2CAV-3).  The number of patients with CAV progression of at least one grade 
while on evolocumab will be compared to historical controls for our transplant program.  
Percentage diameter stenosis for each vessel with visible CAV also will be determined 
by quantitative coronary angiography (QCA) using Philips Xcelera software package in 
a blinded fashion by an experience interventional cardiologist for patients angiograms 
completed one year prior to study entry, at study entry, and study conclusion.  
Angiographic change while on evolocumab therapy will be compared to the preceding 
year. 
 
Assess the effect of evolocumab on immunosuppression regimens and graft rejection.  
Transplant patient are maintained on lifelong immunosuppression.  These agents are 
prone to significant drug-drug interactions which can limit therapies.  Serum levels of 
immunosuppression are monitored every three months per standard protocol.  
Measured serum levels at 3, 6, 9, and 12 months, as well as the number of dose 
adjustments while on evolocumab therapy while on evolocumab therapy will be 
compared to the preceding year.  Statistical adjustment for confounding factors such as 
changes in renal function or other drugs known to alter immunosuppression levels (i.e. 
diltiazem, certain antimicrobial drugs) will be completed.  In addition, the incidence of 
transplant rejection will be documented while on evolocumab therapy and compared to 
the prior year.  Transplant rejection will be defined as symptoms requiring therapeutic 
intervention or endomyocardial biopsy findings of ≥grade 2 or positive C4d staining or 
new donor specific antibodies. 
 
Measure the effect of evolocumab on serum lipids including HDL and triglycerides after 
1 year of therapy.  Fasting lipid profiles (total cholesterol, LDL, HDL and triglycerides) 
after 52 weeks of evolocumab therapy will be compared to baseline levels.  Fasting lipid 
profiles are assessed annually as part of routine post-transplant care.  The percentage 
change of LDL, HDL and triglyceride from baseline will be calculated after 1 year of 
evolocumab therapy. 
 
Statistical analysis is detailed in Section 8 below. 
 
 
 


 
Regulatory oversight 
 
The study will be conducted under the oversight of the University of Nebraska IRB.  An 
independent University of Nebraska Medical Center Data Safety and Monitoring Board 
(DSMB) will be established to monitor participant safety, data quality and evaluate the 
progress of the study. 
 
 
Drug Formulation and Procurement 
 
Study drug (evolocumab) will be provided by Amgen Inc.   While evolocumab is 
commercially available and FDA approved for patient use, storage and distribution in 
this study will be managed by research pharmacy staff at the University of Nebraska.  
Study drug will be stored by research pharmacy staff who will distribute it to patients.  
Study participants receive study drug quarterly directly from research pharmacy staff or 
via courier in temperature-controlled KoolTempGTS coolers (Cold Chain Technologies, 
Franklin, Massachusetts).  Drug accountability will be managed by research 
pharmacists as well. 
 
 
Toxicity and Adverse Event Reporting Guidelines 
 
Evolocumab is currently FDA-approved and commercially available for patient use in 
the United States.  Currently used in patients for the secondary prevention of 
cardiovascular disease and treatment of primary hyperlipidemias, adverse event data is 
available from greater than 27,000 patients enrolled in clinical trials.  Clinical experience 
has shown evolocumab to be well-tolerated with minimal adverse events (see Tables 4 
and 5 below).   
 
Adverse events will be assessed by research personnel at week 2, 4, 12, 26, 38 and 
study conclusion (52).  Events will be obtained either by phone survey or during a 
standard-of-care clinic visit.  Data will be stored and managed using the Forte Electronic 
Data Capture (EDC) software system.  Adverse events will be collected using the 
Common Terminology Criteria for Adverse Event (CTCAE) version 5.0 forms.  Adverse 
events will be quantified and presented by organ system.  Reported events will be 
cataloged and reported to the University of Nebraska IRB and Amgen annually and at 
the conclusion of the study by research personnel.  Reported events will be 
independently reviewed by a cardiology faculty member with significant experience 
prescribing PCSK9 inhibitors.   
 
All suspected unexpected serious adverse reactions (SUSARs) related or possibly 
related to evolocumab and their follow-up reports will be reported to Amgen within 24 
hours of submission to the regulatory agency or IRB.  Amgen will be informed of any 
pregnancy occurring and/or existing during exposure to the investigational medicinal 


product and pregnancies occurring in the partner of a patient participating in the study 
and potential infant exposure within ten (10) calendar days of sponsor awareness. 
 
 
Section 8. Statistical Analysis Plan 
 
Statistical analysis will be completed with the direct assistance of faculty from the 
University of Nebraska biostatistics department. Sample size (n=40) is chosen based on 
the size of the heart transplant clinic (the number of heart transplant patients with CAV 
expected to be eligible for study participation). 
 
The primary outcome is percentage change from the baseline in LDL levels after 12 
weeks of evolocumab therapy.  Prior trials have demonstrated that evolocumab lowers 
LDL cholesterol at week 12 by greater than 50% from baseline[2, 3]. The sample size of 
n=40 is expected to yield greater than 99% power to detect 50% reduction of LDL 
cholesterol from baseline after 12 weeks of evolocumab therapy at a significance level 
of 0.05 using a two-sided Wilcoxon signed-rank test, assuming the estimated standard 
deviation of reduction of 0.17.  
 
Descriptive statistics will be presented as frequencies and percentages for categorical 
variables, and mean ± standard deviation, or median with range for continuous 
variables, unless otherwise indicated. Paired t-tests or Nonparametric Wilcoxon signed-
rank tests will be completed where appropriate to compare the primary endpoint before 
and after 12 weeks of evolocumab therapy, and compare continuous secondary 
endpoints after 1 year of evolocumab therapy to baseline. A linear mixed model analysis 
will be conducted to analyze immunosuppression serum levels measured at baseline, 3 
months, 6 months, 9 months, and 1 year of evolocumab therapy. The binary secondary 
endpoint of CAV progression will be assessed after 1 year of evolocumab therapy using 
McNemar tests. Safety data will be reported with frequencies and percentages. All tests 
will be two-tailed. A p-value <0.05 will be considered significant. Analysis will be 
performed using SAS version 9.4 (SAS Institute, Cary, NC). 
 
Given the limited statistical power due to the small cohort, conclusions from secondary 
endpoints are expected to by primarily hypothesis-generating with data providing 
support for potential future studies. 
 

ICF_001.pdf: 
 
ClinicalTrials.gov Cover Page 
 
 
 
Title: Impact of Evolocumab (Repatha) in Cardiac Transplant Patients with Coronary 
Allograft Vasculopathy (CAV) 
 
ID: NCT03944577 
 
Document date: 11.09.2023 
 
Document: Copy of blank Informed Consent document 
 
 


CONSENT FORM
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ADULT CONSENT - CLINICAL BIOMEDICAL
Adult Consent Form
Title of this Research Study
Invitation
You are invited to take part in this research study. You have a copy of the following,
which is meant to help you decide whether or not to take part:
Informed consent form
"What Do I need to Know Before Being in a Research Study?"
The Rights of Research Subjects
Why are you being asked to be in this research study?
You are being asked to voluntarily participate in this research study because you are
between 19 and 80 years old and have received a heart transplant and have been
diagnosed with mild to moderate coronary allograft vasculopathy (CAV). Participating
in this study is different from receiving regular clinical care. You are encouraged to
ask the investigator or members of the research team any questions you have
regarding this research study. If you decide to participate, you will be asked to sign
this consent form. Participating in research is voluntary, therefore it is your decision
to participate or not. Your decision not to participate will not affect the care you
receive, your relationship with your doctor, or any benefits to which you are entitled.
If you are pregnant, nursing an infant, or plan to become pregnant during this study,
you may not be in this study.
What is the reason for doing this research study?
The purpose of this study is to evaluate if PCSK9 inhibitors improve outcomes for
patients with CAV. CAV is similar to coronary artery disease for patients who have
received a heart transplant. Nearly half of heart transplant patients will develop CAV
after 10 years of receiving a heart transplant. PCSK9 inhibitors are a lipid lowering
therapy currently approved by the United States Food and Drug Administration (FDA)
for patients with coronary artery disease. However, the FDA has not approved the
use of PSCK9 inhibitors for heart transplant patients with CAV. Evolocumab (Brand
name: Repatha) is the PCSK9 inhibitor used in this study.
With this study, we hope to:
Measure the impact of evolocumab on serum LDL in heart transplant patients
Assess the effect of evolocumab on CAV progression
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Assess the effect of evolocumab on immunuosuppression regimens and graft
rejection
Measure the effect of evolocumab on serum lipids after 1 year of therapy
This study is only enrolling patients at Nebraska Medicine/University of Nebraska
Medical Center. Forty subjects are expected to participate. This study is expected to
last two years and individual participation is expected to last 1 year.
What will be done during this research study?
Week 0: If you decide to participate, the study investigator or a member from the
research team will review your medical history with you. This review will include
general health questions, transplant history, CAV history, and transplant rejection
history. You will undergo a medical evaluation and a blood draw to test your
immunosuppressant blood level and lipid panel. The study team will also test your
blood for pregnancy if you are of childbearing potential, and the sponsor will pay for
this test. The results of the pregnancy test will be shared with you as soon as the
results are available. Some of the mentioned tests will be done as part of your
standard care, meaning these tests are typically performed for heart transplant
patients during their annual visit.
Throughout this study, it is important that you notify the investigator if you think you
may be pregnant. If you report that you are pregnant or may be pregnant during your
participation in this study, you will be given a pregnancy test per standard of care.
A study pharmacist will teach you how to self-administer the study drug
subcutaneously using an autoinjector with a needle in your skin either on your upper
arm, stomach, or thigh. The autoinjectors will be mailed to you on a monthly basis,
and you will be directed to self-administer 140mg of the study drug every two weeks
during your participation in this study. If you happen to miss a dose of the study drug
during your participation in this study, please contact a member of the study team or
the investigator for further instruction.
It is important to note that this therapy may be given as an addition to other to other
therapies, such as a prescribed statin or other LDL lowering therapies.
Week 2 and 4: You will be assessed by research personnel for any side-effects or
adverse events. This can be done either by phone survey or during a standard-of-
care clinic visit.
Week 12: You will have follow up visits at week 12, 26, and 38. During these visits,
you will be asked about adverse events, potential side effects, about your compliance
with the study drug. At week 12, a blood samples will be collected to check your lipid
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panel and immunosuppressant blood level. With the exception of the week 12 lipid
panel test, you may be able to complete your blood samples locally if appropriate.
Week 52: The week 52 visit may be scheduled to take place during your routine
annual visit. During your final visit, the investigator or study staff will review your CAV
history, transplant rejection history, and you will undergo a medical evaluation. Blood
samples will be collected to check your immunosuppressant levels and lipid panels
as part of your standard of care.
What are the possible risks of being in this research study?
Risks associated with the study drug: Evolocumab is currently FDA-approved and
commercially available for patient use in the United States. Allergic reactions and
injection-site reactions have occurred in patients using PCSK9 inhibitors.
Other studies have noted risks associated with evolocumab, including muscle-related
events, new-onset diabetes, nasopharyngitis, upper respiratory tract infection,
influenza, back pain, cough, urinary tract infection, sinusitis, headache, myalgia,
dizziness, musculoskeletal pain, hypertension, diarrhea, and gastroenteritis.
Risks associated with blood samples: collection of blood samples may cause
bleeding or leave a bruise at the site of collection. There is a small risk of infection.
Your blood samples will only be collected by trained staff members.
Low LDL Levels: There are potential harmful effects of very low LDL, including
increased risk of neurocognitive disease, increased risk of new-onset diabetes, and
increased risk of malignancy. Clinical trials have yet to demonstrate or validate these
concerns.
Pregnancy: It is unknown if evolocumab is harmful to a fetus or not, and it is unknown
if nursing mothers can pass the study drug through breastmilk. If you are pregnant or
plan to become pregnant during the course of this study, you may not participate in
this study. If you find out you are pregnant or become pregnant during the course of
this study, you must inform the study investigator or research team member
immediately.
It is possible that other rare side effects could occur which are not described in this
consent form. It is also possible that you could have a side effect that has not
occurred before.
What are the possible benefits to you?
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Your condition may improve, it may stay the same, or it could get worse. You may not
get any benefit from being in this research study.
What are the possible benefits to other people?
It is possible that we may learn something from this research study that may help
improve medical treatment for heart transplant patients
What are the alternatives to being in this research study?
Instead of being in this research study, you can choose not to participate. Current
therapies include statin therapy and aspirin therapy. Please ask the study
investigator if you would like more information about alternative treatments.
What will being in this research study cost you?
The sponsor, Amgen, will pay for the study drug; there will be no cost to you for the
study drug. Your insurance company will be billed for standard of care procedures;
You will be responsible for any applicable insurance deductibles and co-payments. If
you wish to speak with a financial counselor about your insurance coverage and
benefits, let the investigator or other study personnel know. A contact for personal
assistance will be made available for you.
Will you be paid for being in this research study?
You will not be paid to be in this research study.
Who is paying for this research?
This research is being paid for by grant funds from Amgen. UNMC/Nebraska
Medicine receives money from Amgen to conduct this study. Dr. Douglas Stoller, the
Principal Investigator of this study, received money for participating on an advisory
board for Amgen, Inc., the sponsor of this study.
What should you do if you are injured or have a medical problem during this
research study?
Your welfare is the main concern of every member of the research team. If you are
injured or have a medical problem as a direct result of being in this study, you should
immediately contact one of the people listed at the end of this consent form.
Emergency medical treatment for this injury or problem will be available at the
Nebraska Medical Center. If there is not sufficient time, you should seek care from a
local health care provider.
The sponsor, Amgen, along with UNMC/Nebraska Medicine have no plans to pay for
any required treatment or provide other compensation. If you have insurance, your
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insurance company may or may not pay the costs of medical treatment. If you do not
have insurance, or if your insurance company refuses to pay, you will be expected to
pay for the medical treatment.
Agreeing to this does not mean you have given up any of your legal rights.
How will information about you be protected?
You have rights regarding the protection and privacy of your medical information
collected before and during this research. This medical information is called
"protected health information" (PHI). PHI used in this study may include your medical
record number, address, birth date, medical history, the results of physical exams,
blood tests, x-rays as well as the results of other diagnostic medical or research
procedures. Only the minimum amount of PHI will be collected for this research. Your
research and medical records will be maintained in a secure manner.
Who will have access to information about you?
By signing this consent form, you are allowing the research team to have access to
your PHI. The research team includes the investigators listed on this consent form
and other personnel involved in this specific study at UNMC/Nebraska Medicine.
Your PHI will be used only for the purpose(s) described in the section "What is the
reason for doing this research study?"
You are also allowing the research team to share your PHI, as necessary, with other
people or groups listed below:
The UNMC Institutional Review Board (IRB)
Institutional officials designated by the UNMC IRB
Federal law requires that your information may be shared with these groups:
The HHS Office for Human Research Protections (OHRP)
The Food and Drug Administration (FDA)
The HIPAA Privacy Rule requires the following groups to protect your PHI:
Your health insurance company
You are authorizing us to use and disclose your PHI for as long as the research
study is being conducted. You may cancel your authorization for further collection of
PHI for use in this research at any time by contacting the principal investigator in
writing. However, the PHI which is included in the research data obtained to date
may still be used. If you cancel this authorization, you will no longer be able to
participate in this research.
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How will results of the research be made available to you during and after the
study is finished?
In most cases, the results of the research can be made available to you when the
study is completed, and all the results are analyzed by the investigator or the sponsor
of the research. The information from this study may be published in scientific
journals or presented at scientific meetings, but your identity will be kept strictly
confidential.
If you want the results of the study, contact the Principal Investigator at the phone
number given at the end of this form or by writing to the Principal Investigator at the
following address:
Douglas Stoller, MD, PhD
982265 Nebraska Medical Center
Omaha, Nebraska
68198-2265
A description of this clinical trial will be available on www.ClinicalTrials.gov, as
required by U.S. law. This website will not include information that can identify you. At
most, the website will include a summary of the results. You can search this website
at any time.
What will happen if you decide not to be in this research study?
You can decide not to be in this research study. Deciding not to be in this research
will not affect your medical care or your relationship with the investigator or
UNMC/Nebraska Medicine. Your doctor will still take care of you and you will not lose
any benefits to which you are entitled.
What will happen if you decide to stop participating once you start?
You can stop participating in this research (withdraw) at any time by contacting the
Principal Investigator or any of the research staff. Deciding to withdraw will otherwise
not affect your care or your relationship with the investigator or UNMC/Nebraska
Medicine. You will not lose any benefits to which you are entitled.
For your safety, please talk to the research team before you stop taking any study
drugs or stop other related procedures. They will advise you how to withdraw safely.
If you withdraw you may be asked to undergo some additional tests. You do NOT
have to agree to do these tests. You may be taken off the study if you do not follow
instructions of the investigator or the research team.
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You may also be taken off the study if you find out you are pregnant or become
pregnant during the course of this study, or the study investigator believes it is in your
best interest. Serious adverse events considered related to treatment, death, and
pregnancy will all result in immediate discontinuation of the study drug. Any research
data obtained to date may still be used in the research. This study may also be
terminated by the investigator or by the sponsor for various reasons including if the
study is stopped by a Health Authority.
Will you be given any important information during the study?
You will be informed promptly if the research team gets any new information during
this research study that may affect whether you would want to continue being in the
study.
What should you do if you have any questions about the study?
You have been given a copy of "What Do I Need to Know Before Being in a
Research Study?" If you have any questions at any time about this study, you should
contact the Principal Investigator or any of the study personnel listed on this consent
form or any other documents that you have been given.
What are your rights as a research participant?
You have rights as a research subject. These rights have been explained in this
consent form and in The Rights of Research Subjects that you have been given. If
you have any questions concerning your rights, or want to discuss problems,
concerns, obtain information or offer input, or make a complaint about the research,
you can contact any of the following:
The investigator or other study personnel
Institutional Review Board (IRB)
Telephone: (402) 559-6463
Email: IRBORA@unmc.edu
Mail: UNMC Institutional Review Board, 987830 Nebraska Medical
Center, Omaha, NE 68198-7830
Research Subject Advocate
Telephone: (402) 559-6941
Email: unmcrsa@unmc.edu
Documentation of informed consent
You are freely making a decision whether to be in this research study. Signing this
form means that:
You have read and understood this consent form.
You have had the consent form explained to you.
Version 2
  IRB
  Approved 11/09/2023
  Valid until 11/09/2024


CONSENT FORM
IRB PROTOCOL # 0104-19-FB
  Page 8 of 9
You have been given a copy of The Rights of Research Subjects
You have had your questions answered.
You have decided to be in the research study.
If you have any questions during the study, you have been directed to talk to
one of the investigators listed below on this consent form.
You will be given a signed and dated copy of this consent form to keep.
Signature of Subject ___________________________
Date ___________
My signature certifies that all the elements of informed consent described on this
consent form have been explained fully to the subject. In my judgment, the subject
possesses the legal capacity to give informed consent to participate in this research
and is voluntarily and knowingly giving informed consent to participate.
Signature of Person obtaining consent ___________________________
Date ___________
Authorized Study Personnel
Principal
* Stoller, Douglas
phone: 402-559-1350
alt #: 402-559-5151
degree: MD, PhD
 
 
Secondary
* Burdorf, Adam (Adam)
phone: 402-559-8049
alt #: 402-888-1058
degree: DO
* Hyden, Marshall
phone: 402-559-1485
alt #: 402-888-6508
degree: MD
 
* Lowes, Brian
phone: 402-559-5530
alt #: 402-559-5151
degree: MD, PhD
* Lundgren, Scott
phone: 402-559-5151
alt #: 402-888-1147
degree: DO
 
* Zolty, Ronald
phone: 402-559-5591
alt #: 402-559-4224
 
Version 2
  IRB
  Approved 11/09/2023
  Valid until 11/09/2024


CONSENT FORM
IRB PROTOCOL # 0104-19-FB
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degree: MD
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Version 2
  IRB
  Approved 11/09/2023
  Valid until 11/09/2024