Clinical trial NCT02839096
Conditions: Anemia in Pregnancy
Sponsor: University of Missouri-Columbia
Start date: 2016-06-01; Completion date: 2019-12-01
Enrollment: 20 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The investigators will randomize women diagnosed with anemia in the mid-trimester of pregnancy to once or twice daily iron supplementation

Detailed description:
Women defined as having iron deficiency anemia based on a low hemoglobin as defined by the American College of Obstetrics and Gynecology and a low serum ferritin, in the absence of hemoglobinopathy, will be randomized to ferrous sulfate 325mg PO daily or PO twice daily.

Arms: arm 1: Randomized to 325mg of ferrous sulfate in the morning and placebo in the evening arm 2: Randomized to 325mg of ferrous sulfate in the morning and 325mg of ferrous sulfate in the evening
Interventions: intervention 1: Placebo intervention 2: Ferrous Sulfate
Intervention descriptions: intervention 1: Cellulose placebo that will be used in place of a second dose of ferrous sulfate in the subjects randomized to once daily dosing of ferrous sulfate intervention 2: Subjects will receive once or twice daily dosing of ferrous sulfate. This will be provided by our hospital pharmacy and be identical in appearance to the placebo.

Protocol documents:
Prot_SAP_000.pdf: 
Jackson 1 
 
Project Title: Once Daily versus Twice Daily Iron Supplementation to Treat Anemia in 
Pregnancy: A Prospective, Randomized, Placebo Controlled, Double Blinded, Clinical 
Trial 
IRB#: 2004638 
Version 8, September 24, 2019 
Principle Investigator: 
Dr. Mistie Mills 
Assistant Professor, Department of Obstetrics and Gynecology 
 
 
 
      
405 N. Keene Street Ste 406 
Summary 
Anemia is a common problem in pregnancy, affecting as many as 1/4 of pregnancies in 
the developed world in the absence of iron supplementation. It is defined as a maternal 
hemoglobin (Hgb) less than 11mg/dL in the 1st or 3rd trimester and Hgb less than 
10.5mg/dL in the 2nd trimester [1].. Anemia  is associated with low birth weight, preterm 
birth, and increased risk for transfusion at the time of delivery [1]. The most common 
cause of anemia in pregnancy is iron deficiency. Iron deficiency anemia in pregnancy is 
typically treated with oral iron supplementation in the form of once or twice daily ferrous 
sulfate, which contains 65mg of elemental iron.  
Iron balance is complex, and iron demands are increased in pregnancy. The fetus, 
placenta, and increased maternal red blood cell volume require about 1g of additional 
iron during the entire pregnancy. The average American diet contains only about 15mg 
of elemental iron, which is insufficient to meet this need[1]. It is recommended that 
pregnant women consume about double this amount during pregnancy[1]. 
The absorption of oral iron is low, ranging from 2-28%. Taking iron without food 
increases absorption. Hepcidin is a key regulator of iron absorption in mammals, 
increasing hepcidin decreases iron absorption. Hepcidin is increased with morning 
fasting dosing, which may affect the efficacy of twice daily dosing (Morretti). Well-
designed clinical trials describing the optimal dosing for iron to treat anemia in 
pregnancy are limited [2, 3].  
A recent publication by Morretti et al [4] evaluated the effect of different doses of oral 
iron in non-pregnant iron deficient young women. They evaluated the effect of varying 
doses of daily ferrous sulfate and once and twice daily dosing of ferrous sulfate on 
hepcidin levels and fractional and total iron absorption. Women were treated with a 
single daily dose ranging from 40-240mg of elemental iron. This 6-fold increase in 
elemental iron dosage only resulted in a 3 fold increase in the amount of elemental iron 
absorbed, contradicting the notion that more iron is better. In a second arm of the study, 
women were treated with twice daily dosing for a total of 180mg of elemental iron. The 
results of the study demonstrated that 24 hours after a dose > 60mg, hepcidin 
increased and fractional iron absorption decreased by 35-45%. Multiple daily 
doses did not increase iron absorption beyond single daily dosing. The authors 
concluded that providing daily dosages less than 80mg of elemental iron and avoiding 


Jackson 2 
 
twice daily dosing maximized iron absorption. The results of the study by Morretti et 
al challenge the conventional wisdom that more severe iron deficiency anemia in 
pregnancy is best treated by increasing from daily to twice daily 
supplementation.  Morretti et al also did not evaluate for gastrointestinal side 
effects or increase in hemoglobin. 
Given the high incidence of iron deficiency anemia in pregnancy and the 
associated complications, we propose a prospective, randomized double blinded 
clinical trial to evaluate the optimal dosing of oral iron supplementation in 
pregnancy. We will recruit mothers identified as having iron deficiency anemia at the 
time of routine prenatal blood work in the second trimester. These subjects will be 
randomized to daily or twice daily ferrous sulfate 325mg (65mg of elemental iron). The 
primary outcomes will be hemoglobin concentration at the time of admission for delivery 
and post-partum and assessment of gastrointestinal side effects. The secondary 
outcome will be frequency of blood transfusion at the time of delivery. 
Hypothesis: Once daily dosing of ferrous sulfate 325mg/dL will be associated with 
increased maternal hemoglobin concentration at the time of delivery and post-partum 
and decreased gastrointestinal side effects. 
Specific Aims 
1. Determine whether once daily dosing of oral iron is more effective in raising 
maternal Hgb concentration than twice daily dosing. 
2. Determine whether once daily dosing of ferrous sulfate 325mg has a lower side 
effect profile than twice daily dosing. 
3. Determine the relationship between frequency of maternal iron administration and 
maternal hepcidin 
4. Determine the relationship between frequency of maternal iron administration and 
fetal iron stores 
Secondary Aim 
Determine whether once daily dosing of ferrous sulfate 325mg is associated with a 
lower rate of maternal blood transfusion at the time of delivery than twice daily 
dosing. 
Inclusion Criteria 
Singleton gestation in the second trimester (14-28 weeks) who is not on iron therapy 
and has a normal hemoglobin electrophoresis if from a high risk group for 
hemoglobinopathy.  
Exclusion Criteria 
Multiple gestation, maternal hemoglobinopathy or hemochromatosis, subjects with 
irritable bowel disease or irritable bowel syndrome, history of bariatric surgery or 
extensive bowel surgery, or individuals already receiving iron supplementation aside 
from prenatal vitamins.  
 


Jackson 3 
 
Study Design 
This will be a prospective, randomized, double blinded placebo controlled clinical trial. 
Subjects will be identified for possible enrollment during the second trimester during 
routine prenatal care. Criteria for enrollment will be a singleton intrauterine gestation as 
above. Subjects without anemia will have weekly questionnaires regarding GI 
symptoms during otherwise scheduled prenatal visits. Subjects with iron deficiency 
anemia as diagnosed by an Hgb concentration of less than 10.5-11mg/dL per ACOG 
guidelines and a ferritin of less than 15mg/dL will be randomized to once or twice daily 
iron supplementation by means of a computer generated random number list by the 
investigational drug pharmacy. The study drug will be provided by the University of 
Missouri Investigational Drug Pharmacy under the guidance of Sonja Grinfeld, the 
Investigational Drug Pharmacist for the University. Iron supplementation will be in the 
form of ferrous sulfate 325mg (65mg of elemental iron) once or twice daily. Anemic 
subjects will receive identical packs of drug with instructions to take one pill BID (twice 
daily). The morning pill will be ferrous sulfate 325mg. The evening pill will be 
randomized to contain either ferrous sulfate 325mg or placebo. The placebo will be 
produced by the investigational drug pharmacy and contain cellulose, a biologically inert 
plant fiber. The subjects and investigators will be blinded to assignment. As part of 
standard Obstetric care, the subject will have a hemoglobin repeated at the time of 
admission to labor and delivery and on post-partum day 1. Subjects who are not anemic 
will serve as controls and not receive a prescription. This is appropriate as the standard 
of care is not to treat non-anemic women with iron supplementation. 
In addition to routine standard of care blood draws, subjects will have two extra samples 
of blood taken for research use at no cost to them. The first will be drawn at the time of 
enrollment, generally at the time of a clinically indicated blood draw for routine prenatal 
labs. The second will be drawn at the time of admission to the hospital for delivery or on 
post partum day 1, again generally at the time of an otherwise clinically indicated blood 
draw. At this time, a separate tube of about 10mL will be drawn for research purposes 
only. A sample of cord blood from the placenta will be obtained following delivery of the 
neonate as well. These samples will be stored for analysis of hepcidin and ferritin at the 
conclusion of the study. These values will be for research use only and will not be used 
in clinical care.  
Subjects will be administered a validated questionnaire regarding gastrointestinal (GI) 
symptoms of iron usage at the time of follow up clinic visits [5]. This questionnaire will 
be administered via RedCap or via paper per patient preference. Compliance will be 
monitored by having the patient bring pill packs to her clinic visits.  
Whether or not the patient required a blood transfusion in the peripartum period will be 
recorded. Due to the relative infrequency of this outcome, this will be evaluated as a 
planned secondary outcome with the understanding that the trial will not be powered 
specifically for this outcome. 
All samples collected will be collected for, stored, and processed by the MU 
Biorepository.  Following study related analysis, the MU Biorepository will de-identify 
what is left of the samples and store the excess for future non-specified research 
endeavors.  


Jackson 4 
 
 
 
Risks and Benefits 
1. Iron therapy is associated with mild gastrointestinal symptoms (upset stomach 
and diarrhea). Increased iron dosage may be associated with an increased risk 
of these symptoms. Significant gastrointestinal symptoms are rare with once or 
twice daily iron dosage. The additional iron in maternal diet (which is classically 
iron poor in the US) or in prenatal vitamins will not pose any additional maternal 
risk. There is no fetal risk to this study. 
2. There are no individual benefits to enrollment in the study. 
 
Subject withdrawal criteria and procedures specifying 
 
a. When and how to withdraw subjects from the trial / investigational product 
treatment. 
If subjects are not compliant with the tasks required in the protocol.  
 
b. The type and timing of the data to be collected for withdrawn subjects. 
All data collected from a withdrawn subject will immediately be destroyed.  
 
c. Whether and how subjects are to be replaced. 
To replace withdrawn subjects, we will recruit another pregnant mother 
d. The follow-up for subjects withdrawn from investigational product treatment/trial 
treatment. 
There will be no follow-up.  
 


Jackson 5 
 
Data handling: 
 
All data will be coded with an ID number. The key containing the ID numbers will be 
kept in a locked file separate from the data.  Data generated from samples tested for 
this study will be stored by the MU Biorepository and by the research staff. . The data 
will be kept for 7 years after study completion. This data will not be shared with outside 
investigators or used for research other than this study.  Additionally, data from this 
study will be included in the Prospective Obstetric Database (PODS) study for future 
use in de-identified fashion.  
 
 
 
Data Analysis 
 
Statistical Analysis: Statistical analyses will be performed using the IBM SPSS statistical 
software version 22 (IBM Corporation, Armonk, NY, USA).  ANOVA will be used to 
assess the difference in mean hemoglobin at the time of admission and post-partum in 
the three arms for the study Regression analysis will be used to explore the 
relationships of iron supplementation on maternal hemoglobin at delivery and fetal 
hemoglobin, hepcidin, and ferritin while controlling for maternal ferritin and hepcidin at 
enrollment. A planned secondary analysis will be to use a Chi-square or Fisher’s exact 
test as appropriate to examine the incidence of blood transfusion during the admission 
for delivery.  Significance will be set at P ≤ 0.05.  
 
Power Analysis: The mean hemoglobin concentration in pregnancy is about 12mg/dL 
and the standard deviation is about 1mg/dL. At an alpha of 0.05 a sample size of 17 
subjects in each arm would be required to have 80% power to detect a difference of 
1mg/dL in maternal hemoglobin. In order to account for subjects lost to follow up due to 
delivery at other facilities, transfer of care and a 20% lost to follow up rate, we will 
continuously enroll subjects until 50 subjects are randomized to treatment in order to 
preserve adequate power to assess our primary outcomes and control for covariates in 
the setting of lost to follow up.  The prevalence of anemia in pregnancy is reported to be 
between 8 and 27% in the second and third trimesters of pregnancy[1]. As such, we 
anticipate a total sample size of around 250 (50 subjects on treatment divided equally 
between once and twice daily iron and 200 controls receiving routine prenatal care. Our 
facility delivers around 2000 patients per year, most of whom receive care in our clinics. 
As such, we anticipate being able to recruit our target sample size, including accounting 
for patient drop out and replacement, in 12-18 months. Based on prior published data 
[5], 10 subjects per arm are required to identify a difference gastrointestinal symptoms.  
 
 
 
Anticipated results and future directions 
 
Based on the increased hepcidin and reduced fractional absorption seen with multiple 
daily dosing, I anticipate that once daily dosing will be superior to twice daily dosing in 


Jackson 6 
 
the treatment of anemia diagnosed during the second trimester of pregnancy. In this 
case, I plan a follow up study to evaluate once versus twice daily dosing in anemia 
diagnosed in the first trimester (1-14 weeks gestation), which is less common but may 
represent a more severe depletion of iron stores. If twice daily dosing is proven to be 
equivalent or superior to once daily dosing in pregnancy, I plan a study similar to 
that of Morretti to determine if the changes in hepcidin levels seen with multiple 
daily doses of iron in the non-pregnant patient are also seen in pregnancy. It is 
possible that pregnant women have a less robust increase in hepcidin in 
response to oral iron and can benefit from increasing dosage. It is also possible 
that they would have a more robust response and would be better served with 
less frequent (i.e.) every other day dosing. I plan to use preliminary data from this 
study to apply for external funds to answer these questions. 
 
The results of this study will be submitted for consideration at the annual meeting of the 
Society for Maternal-Fetal Medicine or the Society of Reproductive Investigation 
depending upon the timeframe in which the study is completed and subsequently 
submitted for publication. 
 
 
 
 
References 
 
1. 
American College of, O. and Gynecologists, ACOG Practice Bulletin No. 95: anemia in pregnancy. 
Obstet Gynecol, 2008. 112(1): p. 201-7. 
2. 
Pena-Rosas, J.P., et al., Daily oral iron supplementation during pregnancy. Cochrane Database 
Syst Rev, 2015. 7: p. CD004736. 
3. 
Pena-Rosas, J.P., et al., Intermittent oral iron supplementation during pregnancy. Cochrane 
Database Syst Rev, 2015. 10: p. CD009997. 
4. 
Moretti, D., et al., Oral iron supplements increase hepcidin and decrease iron absorption from 
daily or twice-daily doses in iron-depleted young women. Blood, 2015. 126(17): p. 1981-9. 
5. 
Pereira, D.I., et al., A rapid, simple questionnaire to assess gastrointestinal symptoms after oral 
ferrous sulphate supplementation. BMC Gastroenterol, 2014. 14: p. 103. 
 

ICF_001.pdf: 
Page 1 of 8 
 
IRB USE ONLY 
Approval Date: October 4, 2019 
 
 CONSENT FORM TO PARTICIPATE IN A RESEARCH STUDY  
INVESTIGATOR’S NAME: Mistie Mills, M.D., M.S. PROJECT # 2004638  
 
Study Title: Once Daily versus Twice Daily Iron Supplementation to Treat Anemia in 
Pregnancy: A Prospective, Randomized, Placebo Controlled, Double Blinded, Clinical Trial  
 
INTRODUCTION  
 This consent may contain words that you do not understand. Please ask the investigator or the 
study staff to explain any words or information that you do not clearly understand.  
 
This is a research study. Research studies include only people who choose to participate. As a study 
participant you have the right to know about the procedures that will be used in this research study so 
that you can make the decision whether or not to participate. The information presented here is 
simply an effort to make you better informed so that you may give or withhold your consent to 
participate in this research study.  
 
Please take your time to make your decision and discuss it with your family and friends.  
 
You are being asked to take part in this study because you are pregnant and being tested for anemia 
as part of routine clinical care. Anemia means a low number of red blood cells. Anemia in pregnancy 
is treated with pills containing iron.  
 
In order to participate in this study, it will be necessary to give your written consent.  
 
WHY IS THIS STUDY BEING DONE?  
The purpose of this study is to determine the best dosage of iron pills to treat anemia in pregnancy.  
 
HOW MANY PEOPLE WILL TAKE PART IN THE STUDY?  
About 250 people will take part in this study at the University of Missouri. There are no other study 
sites.  
 
WHAT IS INVOLVED IN THE STUDY?  
You will be tested for anemia as part of your normal prenatal care. If you are found to be anemic, 
you will be “randomized” into one of the study groups described below. Randomization means that 
you are put into a group by chance. It is like flipping a coin. Neither you nor the researcher will 
choose what group you will be in. You will have an equal chance of being placed in either group. If 
you are not anemic, you will have routine clinical care, be asked to complete a survey 3-5 times 
during the remainder of your pregnancy, and will not be randomized to a treatment group.  
 
If you take part in this study, you will have the following tests and procedures:  
 


Page 2 of 8 
 
IRB USE ONLY 
Approval Date: October 4, 2019 
If you have anemia, you will be randomized to take a single iron pill either once daily (before 
breakfast on an empty stomach) or twice daily (before breakfast on an empty stomach and before 
your evening meal on an empty stomach).  
• The amount of iron given in each group is part of the standard care which may be done even if you 
do not join the study. Both groups will take two pills; one of those pills will be placebo for the group 
randomized to a single iron pill once daily.  
• Your blood count will be monitored in this study in the same fashion as if you are not in the study.  
• Whether you are anemic or not, you will have two additional blood samples drawn for use in the 
study. One will be drawn at enrollment and one at the time of admission to the hospital when you are 
going to deliver your baby. If possible, these blood draws will be done when you are having blood 
drawn for a routine clinical test.  
• A sample of blood will be taken from the umbilical cord following delivery for research use as 
well.  
 
Each of these blood draws will be about 10cc (1 tube). There will be no cost to you for these 
additional samples.  
 
We will keep the information we collect from you for this study to use in future research and to share 
with other investigators to use in future studies without asking for your consent again. Information 
that could identify you will be removed from your research data so no one will know that it belongs 
to you.  
 
HOW LONG WILL I BE IN THE STUDY?  
We think you will be in the study from enrollment until delivery, approximately 14-20 weeks.  
The investigator and/or your doctor may decide to take you off this study if you are unable to comply 
with taking the study medication as prescribed.  
 
You can stop participating at any time. Your decision to withdraw from the study will not 
affect in any way your medical care and/or benefits. If you decide to stop participating in the 
study, you are encouraged to discuss your decision with your doctor. There are no health 
consequences from withdrawing from the study. If you do withdraw, you will be advised to 
continue taking oral iron therapy. Your data will not be used in the calculation of study results.  
 
WHAT ARE THE RISKS OF THE STUDY?  
While on the study, you are at risk for the side effects described below. You should discuss these 
with the investigator and/or your doctor. There may also be other side effects that we cannot predict. 
You may receive other drugs to make side effects less severe and uncomfortable. Many side effects 
go away shortly after the iron is stopped. Long lasting or serious side effects have not been reported 
with iron therapy.  
 
Risks and side effects related oral iron therapy include:  
 
Those seen in >10% of individuals taking iron sulfate:  
 
Gastrointestinal: Constipation, dark stools, epigastric pain, GI irritation, nausea, stomach cramping, 
vomiting  


Page 3 of 8 
 
IRB USE ONLY 
Approval Date: October 4, 2019 
Those seen in 1-10% of individuals taking iron sulfate:  
Gastrointestinal: Diarrhea, heartburn  
Genitourinary: Discoloration of urine  
Miscellaneous: Liquid preparations may temporarily stain the teeth  
Those seen in <1% of individuals taking iron sulfate (Limited to important or life-threatening):  
 
Contact irritation  
 
For the reasons stated above the investigator will observe you closely while giving the treatment 
described and, if you have any worrisome symptoms or symptoms that the investigators or their 
associates have described to you, notify the investigator(s) immediately. Dr. Mill’s  telephone 
number is 573- 499-6084   
 
In clinical trials where you and the investigator do not know what dose of medication you are given, 
there will be a way to discover which treatment you are receiving if your condition worsens. The 
pharmacy will keep a record of which patients are assigned to which dose of iron, and they can be 
contacted at any time to reveal the patient’s dosage.  
 
ARE THERE BENEFITS TO TAKING PART IN THE STUDY?  
If you agree to take part in this study, there is no direct medical benefit to you. You may expect to 
benefit from taking part in this research to the extent that you are contributing to medical knowledge. 
We hope the information learned from this study will benefit other patients with anemia in pregnancy 
in the future.  
 
There is no guarantee that taking part in this research will result in any improvement in your 
condition.  
 
WHAT OTHER OPTIONS ARE THERE?  
Instead of being in this study, you have these options:  
Oral iron therapy at a dose suggested by your provider would be recommended. You are free to 
decline treatment for your anemia.  
An alternative is to not participate in this research study.  
 
WHAT ABOUT CONFIDENTIALITY?  
A copy of this consent will be placed in the medical record. Anyone accessing your record will be 
able to view the document and see that you have agreed to participate in the study. Medical 
information produced by this study will become part of your hospital medical record. Information 
that does not become part of your medical record will be stored in the investigator’s file and 
identified by a code number only. The code key connecting your name to specific information about 
you will be kept in a separate, secure location. Information contained in your records may not be 
given to anyone unaffiliated with the University of Missouri in a form that could identify you without 
your written consent, except as required by law. If the investigator conducting this study is not your 
primary, or regular doctor, the investigator must obtain your permission before contacting your 
regular doctor for information  
 


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IRB USE ONLY 
Approval Date: October 4, 2019 
about your past medical history or to inform them that you are in this trial.  


Page 5 of 8 
 
IRB USE ONLY 
Approval Date: October 4, 2019 
 
It is possible that your medical and/or research record, including sensitive information and/or 
identifying information, may be inspected and/or copied by the study sponsor (and/or its agent), the 
Food and Drug Administration (FDA), federal or state government agencies, or hospital accrediting 
agencies, in the course of carrying out their duties.  
 
If your record is inspected or copied by the study sponsor (and/or its agents), or by any of these 
agencies, the University of Missouri will use reasonable efforts to protect your privacy and the 
confidentiality of your medical information.  
 
The results of this study may be published in a medical book or journal or used for teaching 
purposes. However, your name or other identifying information will not be used in any publication or 
teaching materials without your specific permission.  
 
State and federal privacy laws (HIPAA) protect the use and release of your health information. If you 
decide to take part in this study, you also give us your permission to use your private health 
information, including the health information in your medical records and information that can 
identify you.  
 
You have the right to refuse to give us your permission for us to use your health information. 
However, doing so would mean that you could not take part in this study.  
 
The following identifiers will be obtained from your health records:  
 Name  
 Dates related to you  
 Medical Record Number  
 
The following is the type of protected health information that will be used in the study:)  
 Discharge Summaries Medications  
 Progress Notes History and Physical Exams  
 Questionnaires, Surveys, Diaries Laboratory Reports  
 Demographics (age, race, etc.)  
 
Your permission for us to use and release your information will not expire unless you cancel your 
permission.  
 
You can cancel your permission at any time by writing to:  
Investigator’s Name: Mistie Mills, MD  
Institution: University of Missouri  
Department: Obstetrics, Gynecology and Women’s Health  
Address: 500 N Keene Street, Ste 405 Columbia Mo, 65201 
 
The information we have already collected may still be used for this research study, but we will not 
collect anymore information after we receive your letter.  


Page 6 of 8 
 
IRB USE ONLY 
Approval Date: October 4, 2019 
You have the right to access your protected health information that is obtained or created during this 
research project until the end of study ends.  
If you have not already received a copy of the University of Missouri Healthcare Privacy Notice, you 
may request one. If you have any questions or concerns about your privacy rights, you may contact 
the Privacy Officer at 573-882-9054.  
 
WHAT ARE THE COSTS?  
There is no cost to you for enrolling in the study itself. Your study drug will be provided at no cost to 
you. No procedures or laboratory studies will be performed that are not part of routine prenatal care.  
In addition, the use of other medications to help control side effects could result in added costs that 
may or may not be covered by your medical insurance.  
 
Please note that added costs may include insurance co-payments for doctor visits, transportation, 
parking, and/or other possible expenses during your participation in this study. Please discuss these 
issues with the study investigator and/or your doctor.  
 
You will not be charged for any tests that are part of this research study beyond what you are being 
charged for routine prenatal care. You or your insurance company will, however, be charged for any 
other portion of your care that is considered standard care. 
  
You or your insurance company will be charged for continuing medical care and/or hospitalization.  
 
WILL I BE PAID FOR PARTICIPATING IN THE STUDY?  
You will receive no payment for taking part in this study.  
 
WHAT IF I AM INJURED?  
It is not the policy of the University of Missouri to compensate human subjects in the event the 
research results in injury. The University of Missouri, in fulfilling its public responsibility, has 
provided medical, professional and general liability insurance coverage for any injury in the event 
such injury is caused by the negligence of the University of Missouri, its faculty and staff. The 
University of Missouri also will provide, within the limitations of the laws of the State of Missouri, 
facilities and medical attention to subjects who suffer injuries while participating in the research 
projects of the University of Missouri. In the event you have suffered injury as the result of 
participation in this research program, you are to contact the Risk Management Officer, telephone 
number (573) 882-1181, at the Health Sciences Center, who can review the matter and provide 
further information. This statement is not to be construed as an admission of liability.  


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IRB USE ONLY 
Approval Date: October 4, 2019 
WHAT ARE MY RIGHTS AS A PARTICIPANT?  
Participation in this study is voluntary. You do not have to participate in this study. Your 
present or future care will not be affected should you choose not to participate. If you decide to 
participate, you can change your mind and drop out of the study at any time without affecting your 
present or future care in the University of Missouri. Leaving the study will not result in any penalty 
or loss of benefits to which you are entitled. In addition, the investigators of this study may decide to 
end your participation in this study at any time after he or she have explained the reasons for doing so 
and has helped arrange for your continued care by your own doctor, if needed.  
 
You will be informed of any significant new findings discovered during the course of this study that 
might influence your health, welfare, or willingness to continue participation in this study.  
A description of this clinical trial will be available on www.ClinicalTrials.gov, as required by U.S. 
law. This Web site will not include information that can identify you. At most, the Web site will 
include a summary of the results. You can search this Web site at any time.  
 
WHOM DO I CALL IF I HAVE QUESTIONS OR PROBLEMS?  
For questions about the study or a research related injury, contact Dr. Mistie Mills 
at 573-499-6084 
You may also contact the University of Missouri Institutional Review Board (IRB) if you:  
• 
Have any questions about your rights as a study participant;  
• 
Want to report any problems or complaints; or  
• 
Feel under any pressure to take part or stay in this study.  
 
The IRB is a group of people who review research studies to make sure the rights of participants are 
protected. Their phone number is 573- 882-3181.  
If you want to talk privately about your rights or any issues related to your participation in this study, 
you can contact University of Missouri Research Participant Advocacy by calling 888-280-5002 (a 
free call), or emailing MUResearchRPA@missouri.edu.  
A copy of this consent form will be given to you to keep.  
 
SIGNATURE  
 
I confirm that the purpose of the research, the study procedures, the possible risks and discomforts as 
well as potential benefits that I may experience have been explained to me. Alternatives to my 
participation in the study also have been discussed. I have read this consent form and my questions 
have been answered. My signature below indicates my willingness to participate in this study. 
 
 
__________________________________________________ 
____________ 
Signature 
 
 
 
 
 
 
 
Date 
 
*The presence and signature of an impartial witness is required during the entire informed consent 
discussion if the patient or patient’s legally authorized representative is unable to read.  
 
_____________________________________________________ 
_____________ 
Witness ( if required) 
 
 
 
 
 
 
Date 
 


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IRB USE ONLY 
Approval Date: October 4, 2019 
 
 
_______________________________________________________ 
______________ 
 
SIGNATURE OF STUDY REPRESENTATIVE  
 
 
Date 
I have explained the purpose of the research, the study procedures, identifying those that are 
investigational, the possible risks and discomforts as well as potential benefits and have answered 
questions regarding the study to the best of my ability.