Clinical trial NCT03459794
Conditions: Ivermectin
Sponsor: University of Georgia
Start date: 2018-02-12; Completion date: 2018-11-30
Enrollment: 12 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
We hypothesize that ivermectin, a drug used to treat parasitic worm infections, interacts with the human innate immune system and that this contributes to its anti-parasitic effects. Participants will donate blood before and after being administered the normal human dose of the drug. We will compare the cell types present in the blood and the chemicals known to influence the human immune system before and after the drug is given, as well as measuring any changes in gene expression in white blood cells 4 and 24hrs after the drug is taken.

Detailed description:
Subjects will visit the University of Georgia (UGA) Clinical \& Translation Research Unit (CTRU) twice on consecutive days and blood will be drawn from them. On the first occasion they will be weighed and will complete the consent process. They will have been randomly assigned to the test (Stromectol) or control (placebo) group, with 8 participants in the test group and 4 participants in the control group. Stromectol will be obtained from a medical supply distributor and a placebo will be obtained through the UGA School of Pharmacy. Drugs will be prescribed by Jonathan Murrow MD. They will be stored in their original packaging at room temperature in a drug locker in the lab at CTRU. Participants will be identified by number and allocated to groups using a block randomization protocol. Randomization and drug dispensation will be done by CTRU. Eighteen ml of blood will drawn in a fasting state and they will be administered 150 mcg/kg Stromectol or the equivalent number of placebo tablets immediately after blood is drawn. Participants will remain at CTRU for four hours after they take the drug, then another 15ml of blood will be drawn. On the second day they will attend CTRU at the same time and the third blood sample will be drawn 24 hrs after administration of the drug. On each occasion the drawn blood will be coded by CTRU staff prior to being collected by a member of the Department of Infectious Diseases and taken to the laboratory (Wildlife Health G0007) for the isolation of leukocyte populations (peripheral monocytes, lymphocytes and polymorphonuclear cells (PMNs)) and for the preparation of serum. Complete blood counts will also be carried out. Sera will be analyzed on the Luminex for cytokine/chemokine content. RNA will be isolated from the cell populations for RNASeq analysis.

Arms: arm 1: Ivermectin will be administered once at 150mcg/kg, orally. arm 2: An oral placebo will be administered once
Interventions: intervention 1: Ivermectin intervention 2: Placebo
Intervention descriptions: intervention 1: 150 mcg/kg ivermectin, by mouth. intervention 2: An oral placebo will be administered, once

Protocol documents:
Prot_SAP_ICF_000.pdf: 
Cover Sheet 
 
Clinicaltrials.gov ID   NCT03459794 
Ivermectin and human immunity 
Protocol 
ID#STUDY00005069 
PI: 
Adrian 
Wolstenholme 
Primary Contact: 
Adrian 
Wolstenholme 
Submission 
Type: 
Initial Study 
 
 
IRB 
Coordinator: 
Brooke Harwell  
Parent Protocol: 
 
Review 
Category: 
 
 
 
Approved 
Date: 
9/27/2017 
 
 
Expiration 
Date: 
7/11/2018 
 
 
   


Date: Monday, November 26, 2018 12:06:50 PM
View: SF: Basic Information UGA v2
Section 1 - Basic Information
1.
* Title of Study:
The effects of ivermectin on the normal human
immune system
If the study is/will be funded, the IRB recommends
matching the title in the funding proposal. 
2.
* Short Title:
Ivermectin and human immunity
This can match the long title or be shortened if your
project uses an acronym or nickname; however, all
system generated lists, searches, and documents
(including approval letters) will show the short title. 
3.
Principal Investigator (faculty or senior
staff only - see help):
Adrian Wolstenholme
Only UGA faculty and selected staff members (senior
staff) are eligible to serve as PI.  See the policy for
more information: http://research.uga.edu/documents
/eligibility
4.
* Does the Principal Investigator have a
financial interest related to this
research?
Yes
No
See the policy for more
information: https://research.uga.edu/docs/policies
/compliance
/hso/PP_Financial%20Conflicts%20of%20Interests.pdf
5.
* Are you requesting determination if
your project meets the definition of
human subjects research?
Yes
No
Are you requesting determination if
your project meets the criteria for
developmental review?
Yes
No
Will an external IRB act as the IRB of
record for this study?
Yes
No
If you are not sure if your project needs IRB
review, choose "Yes" in the first question.  A form will
open and provide prompts to guide you through
an initial assessment to see if your project needs IRB
review.
If you are seeking external funding and the sponsor or
the Office for Sponsored Programs requests for IRB
approval but you are not ready to create materials for
the human subject research activities, choose "Yes" in
the second question.  A form will open and provide
prompts to guide you through an initial assessment to
see if you can receive a letter from the IRB without
completing a full submission for review. 
If you are collaborating with other institutions and the
collaboration model involves review by a central IRB,
and UGA is not the lead institution, choose "Yes" on
the third question.  Be prepared to submit information
that the other IRB will review.
Print: STUDY00005069 - Ivermectin and human immunity
https://ovpr-click-prod.ovpr.uga.edu/uga-ovpr/ResourceAdministration/P...
1 of 24
26-Nov-18, 12:07


View: UGA SF: Project Funding Details
Project Funding Details
1.0
Mark all that apply: Identify below if the study is/will be supported in
whole or in part. If the funding has not been awarded yet, mark pending.
Check all that apply. If you have not applied for funding or have no plan to
at the time of initial submission, mark “No Funding” and continue to the
next page.  If you will or have applied for funding, choose Externally
Funded or Internally Funded depending on the source (see Help on right.) 
If the funding has not been awarded yet, mark “Pending.”  Finally, indicate
whether UGA is/will be the prime awardee or a sub-award/contract.
Funding Status:
No Funding
Externally Funded
Internally Funded
Pending
Primary Awardee is UGA
Sub-Award or Sub-Contract to UGA
Internal sources
include UGA
departments or
institutes.  External
sources may be
federal agencies
(e.g., NIH, NSF),
industry sponsors
(e.g., Novartis), or
private sponsors
(e.g., Bill and
Melinda Gates
Foundation.)
2.0
Identify each funding source.  If you have more than one, add each
separately.  If the sponsor agency is not in the selection list, choose TBD
and identify the source in Q5.  The Grants Office ID number is required: 
this is the Grants Portal Project ID (FP000XXXX) or Award ID
(AWD000XXXX.)
Funding Source
Sponsor's
Funding ID
Grants
Office ID
Attachments
Clinical & Translational
Research Unit
CTRU Seed Grant RFP
FY18.docx
The IRB must
review any funding
proposal, contract,
or sub-contract for
congruence with the
description of
human subjects
activities described
in this submission. 
The funding
proposal or draft
contract must be
provided.
3.0
Name of Project and/or Project PI if different from this IRB submission.
4.0
Describe the scope of this IRB submission compared to the grant
proposal (sub-award or statement of work) related to this project.
Scope of Application:
All human subjects activities in the grant proposal are covered in this
IRB Application.
Not all human subjects activities in the grant proposal are covered in this IRB
Application; however, these activities will be covered in future UGA IRB
Application(s).
Not all human subjects activities in the grant proposal are covered in this IRB
Application; however, these activities have been covered in another UGA IRB
Application. Identify the UGA PI (if different from PI of this IRB Application)
and the IRB Project Number below.
Not all human subjects activities in the grant proposal are covered in this IRB
Application; however, these activities have been or will be reviewed by
another institution’s IRB. Identify the PI and name of the other institution
below.
Other, please explain.
5.0
Provide any additional information as requested above.
This submission is associated with an application to the CTRU Seed
Funding Program.
Print: STUDY00005069 - Ivermectin and human immunity
https://ovpr-click-prod.ovpr.uga.edu/uga-ovpr/ResourceAdministration/P...
2 of 24
26-Nov-18, 12:07


View: UGA SF: Study Team Members
Study Team Members
1.0
Identify each UGA faculty, staff, or student who will be engaged in the conduct of human research. Do
not select the PI again.
Name
Roles
Financial
Interest
Involved
in
Consent
E-mail
Phone
IsStudentProject
View Maisie
Anderson-
Frost
RESEARCH
COORDINATOR
no
yes
Maisie.AndersonFrost@uga.edu 706-713-2722
View ROBERT
CAPITANO
RESEARCH
COORDINATOR
no
yes
salvator@uga.edu
706-713-2722 no
View KRISTIN
Capitano
RESEARCH
COORDINATOR
no
yes
capitano@uga.edu
706-713-2722 no
View STEPHANIE
CROYLE
RESEARCH
COORDINATOR
no
yes
scroyle@uga.edu
706-713-2732 no
View Jennifer
Dunlop
RESEARCH
COORDINATOR
no
no
jdunlop@uga.edu
706-713-2722
View TEJAL HILL RESEARCH
COORDINATOR
no
yes
tejalh@uga.edu
706-713-2722
View Jonathan
Murrow
CO-
INVESTIGATOR
no
yes
jmurrow@uga.edu
706-542-4378 no
View Barbara
Reaves
CO-
INVESTIGATOR
no
no
bjreaves@uga.edu
706-542-6516 no
View ANGELIA
ROGERS
RESEARCH
COORDINATOR
no
yes
alorrain@uga.edu
View Kimberly
Schmitz
RESEARCH
COORDINATOR
no
yes
schmitzk@uga.edu
706-713-2722 no
2.0
Identify non-UGA collaborators* who will be engaged in the conduct of human research.
Name
Email
Organization
There are no items to display
*Submit an Individual Investigator Agreement for all study personnel with an institution that does not have an assurance with the
Office for Human Research Protections or OHRP (typically, local schools, private doctors, clinics).
*For study personnel who are affiliated with an institution that has an assurance (has its own IRB), do not submit an Individual
Investigator Agreement.  Instead indicate that you have an External Site on the Study Scope page.
If the collaborator
has not
completed
human subjects
research training,
contact your
business
department to
get a UGA
MyID for
them. Note: The
Individual
Investigator
Agreement is not
required for
projects that will
be submitted for
Exempt
determination
(see Study
Scope page).
Print: STUDY00005069 - Ivermectin and human immunity
https://ovpr-click-prod.ovpr.uga.edu/uga-ovpr/ResourceAdministration/P...
3 of 24
26-Nov-18, 12:07


View: UGA SF: CITI Training Records
Study Team Members CITI Training Records
1.0
Principal Investigator (PI):Adrian Wolstenholme
Job Title: PROFESSOR
Please note: The training records update three times daily. Depending on when the course is
completed or updated, the record may not be uploaded until 24 hours later.
PI CITI Courses:
Stage
Group
Date Taken
Expiration Date
1 - Basic Course
Bio-Medical Research
6/7/2012
6/7/2017
2 - Refresher Course
Bio-Medical Research
7/3/2017
7/3/2022
If a record does not
display for someone
that has completed
training, try
removing/deleting
that person and
adding them again
on the Basic Info
page (PI) or Study
Team Member page.
2.0
Study Team Members:
Person
Group
Stage
Expiration
Date
Maisie Anderson-Frost
Bio-Medical
Research
1 -
Basic
Course
10/19/2022
Person
Group
Stage
Expiration
Date
ROBERT CAPITANO
Social &
Behavioral
Research
1 -
Basic
Course
3/1/2022
Bio-Medical
Research
1 -
Basic
Course
5/12/2021
Person
Group
Stage
Expiration
Date
KRISTIN Capitano
Bio-Medical
Research
1 -
Basic
Course
2/18/2021
Person
Group
Stage
Expiration
Date
STEPHANIE CROYLE
Bio-Medical
Research
1 -
Basic
Course
6/21/2021
Person
Group
Stage
Expiration
Date
Jennifer Dunlop
Bio-Medical
Research
1 -
Basic
Course
12/14/2021
Person
Group
Stage
Expiration
Date
TEJAL HILL
Social &
Behavioral
Research
1 -
Basic
Course
5/28/2020
Social &
Behavioral
Research -
Prisoners
1 -
Basic
Course
5/28/2020
Bio-Medical
Research
1 -
Basic
Course
10/24/2022
Person
Group
Stage
Expiration
Date
Jonathan Murrow
Bio-Medical
Research
1 -
Basic
Course
4/15/2019
IRB Members
1 -
Basic
Course
3/5/2023
If any study team
member including
the PI has either not
completed training
or has not linked
previously-
completed training
to a valid UGAID,
the record will show
"There are no items
to display".
The application will
not successfully
submit to the IRB if
the training
requirement is not
met.  Likewise, if
training has expired
and a refresher
course has not been
completed or the
training will expire in
less than 90 days,
the application will
not sucessfully
submit to the IRB.
Print: STUDY00005069 - Ivermectin and human immunity
https://ovpr-click-prod.ovpr.uga.edu/uga-ovpr/ResourceAdministration/P...
4 of 24
26-Nov-18, 12:07


Person
Group
Stage
Expiration
Date
Barbara Reaves
Bio-Medical
Research
1 -
Basic
Course
7/8/2019
Person
Group
Stage
Expiration
Date
ANGELIA ROGERS
Bio-Medical
Research
1 -
Basic
Course
1/12/2021
Person
Group
Stage
Expiration
Date
Kimberly Schmitz
Social &
Behavioral
Research
1 -
Basic
Course
11/13/2018
Bio-Medical
Research
1 -
Basic
Course
8/31/2020
SF
Print: STUDY00005069 - Ivermectin and human immunity
https://ovpr-click-prod.ovpr.uga.edu/uga-ovpr/ResourceAdministration/P...
5 of 24
26-Nov-18, 12:07


View: SF: Study Scope
Study Scope
1.0
Will you recruit or conduct the study at a non-UGA agency/institution
/facility (i.e., referred to as an External Site) where you do not normally
have research privileges?
Yes
No
Answer "Yes" if you
will recruit from a local
public or private
school, medical
practice, community
agency/organization,
or will conduct your
procedures at any of
these.
2.0
Does  the study do any of the following:
Specify the use of an approved drug or biologic?
Use an unapproved drug or biologic?
Use a food or dietary supplement to diagnose, cure, treat, or
mitigate a disease or condition?
Use a food or dietary supplement only to evaluate the dietary
supplement's effect on the structure or function of the body?
Yes
No
3.0
Does the study do any of the following:
Evaluate the safety or effectiveness of a device?
Use a humanitarian use device (HUD)?
Yes
No
4.0
Check all that apply:
Project is Exempt (see Help Text on right)
Internet Research
Research activities are limited to analysis of data
Deception, concealment, or incomplete disclosure
HIPAA (Protected Health Information)
Blood Sampling/Collection
Genetic Analysis
DXA/X-Ray
More than moderate Exercise
Electrical Stimulation
Clinical Trial
Data/Tissue Repository
Be sure to mark the
first box if the study
may meet criteria for
exemption.  More
information about
exemption is available
in the Policy and
Procedure:  Exempt
Review in the Library
or on the website at
http://research.uga.edu
/hso/irb-guidelines/
Print: STUDY00005069 - Ivermectin and human immunity
https://ovpr-click-prod.ovpr.uga.edu/uga-ovpr/ResourceAdministration/P...
6 of 24
26-Nov-18, 12:07


View: UGA SF: Drugs
Drugs
1.0
List all drugs, biologics, foods, and dietary supplements to be used in the
study.
Generic Name
Brand Name
Attachment Name
View Ivermectin
STROMECTOL
stromectol_pi.pdf
2.0
Will the study be conducted under any IND Numbers
Yes
No
If so, identify each IND:
IND Number
IND Holder
Other Holder
There are no items to display
3.0
If your study will not be conducted under an IND number, it must meet all
of the following six criteria for an IND exemption.  Carefully evaluate each
criterion and check the box if it applies to your study.
The investigation does not involve a route of administration, dose, patient
population, or other factor that significantly increases the risk (or decreases the
acceptability of the risk) associated with the use of the drug product (21 CFR
312.2(b)(1)(iii)).
The investigation is not intended to be reported to FDA as a well-controlled study
in support of a new indication and there is no intent to use it to support any
other significant change in the labeling of the drug.
The investigation is conducted in compliance with the requirements for review by
an IRB (21 CFR part 56) and with the requirements for informed consent (21 CFR
part 50).
The drug product is lawfully marketed in the United States.
The investigation is conducted in compliance with the requirements of § 312.7
(i.e., the investigation is not intended to promote or commercialize the drug
product).
In the case of a prescription drug, the investigation is not intended to support a
significant change in the advertising for the drug.
4.0
Attach files (such as IND or other information that was not attached for a
specific drug).
Document
Category
Date
Modified
View Exemption
Criteria.docx(0.01)
Drug
Attachment
8/18/2017
Print: STUDY00005069 - Ivermectin and human immunity
https://ovpr-click-prod.ovpr.uga.edu/uga-ovpr/ResourceAdministration/P...
7 of 24
26-Nov-18, 12:07


View: UGA SF: Blood Sampling/Collection
Blood Sampling/Collection
1.0
Choose the method(s) of blood collection.
Venipuncture
2.0
For participants who are healthy, non-pregnant adults weighing at least 110 pounds:
Will blood be collected more than 2 times per week?
Yes
No
Will the amount of blood drawn exceed 550 ml in an 8 week period?
Yes
No
If the answer to
either question is
"Yes", this project
will be reviewed via
committee at a
convened meeting.
3.0
For other adults and children:
Will blood be collected more than 2 times per week?
Yes
No
Will the amount of blood drawn exceed the lesser of 50 ml or 3 ml/kg in an
8 week period?
Yes
No
If the answer to
either question is
"Yes", this project
will be reviewed via
committee at a
convened meeting.
4.0
Indicate the specific volume and frequency (or the schedule) of blood
collection.
Blood will be drawn immediately before subjects take an oral dose of ivermectin, then again 4
and 24 hours later. 30 mls of blood will be drawn on each occasion. Only healthy, non-
pregnant adults weighing more than 110 pounds and less than 185 pounds will be recruited
as donors
5.0
Describe the specific collection procedures, including the use of sterile
techniques and adherence to standard laboratory safety practices.
The blood samples will be collected utilizing standard procedures at the CTRU,
utilizing all sterile equipment and adhering to standard lab safety practices
6.0
Personnel performing blood draws must have sufficient training and
experience in conducting human blood sampling.  Describe who will
collect the blood and this person's experience/training in the specific
blood collection procedures.
Research nurses associated with the CTRU will collect the blood. CTRU nurses
have extensive training and experience in phlebotomy.
7.0
If participants will be asked to fast prior to blood collection(s), describe
how and when informed consent will be obtained prior to fasting.
It is recommended that Stromectol be administered on an empty stomach, so
participants will be asked to fast for two hours prior to the first blood draw.
Informed consent will be obtained during the screening interview.
If consent is
obtained without
requiring the
participant to sign a
consent form, be
sure to request for a
waiver of the
requirement to
document informed
consent on the
Consent Process
page.
8.0
Describe why it is important to collect blood for this study, including the
specific analysis that will be conducted on the blood samples.
We are studying the effects of Stromectol on the human immune system, so
blood is required for analysis of both cytokines and leukocyte gene expression
following drug administration. Cytokines and chemokines will be determined
using Luminex and a commercial kit. Leukocyte populations will be separated into
peripheral blood mononuclear cells (PBMC) and polymorphonuclear cells (PMN)
and RNA extracted for RNASeq analysis. We will also test the ability of the PBMC
and PMN populations to attach to, and kill, Brugia malayi microfilariae.
The consent
document should
also describe the
type of analyses that
will be conducted
and should
specifically state
whether or not the
sample will be
analyzed for
HIV/AIDS.
9.0
Describe the plan for disposition of any unused blood, including when
and how unused samples will be disposed of.
Unused blood will be disposed of by incineration as soon as practicable after the
If samples will be
retained for future
analyses, the future
Print: STUDY00005069 - Ivermectin and human immunity
https://ovpr-click-prod.ovpr.uga.edu/uga-ovpr/ResourceAdministration/P...
8 of 24
26-Nov-18, 12:07


cells have been isolated.
use must be
described in the
consent document
and the
additional/future use
can be made
optional via a tiered
consent statement.
Print: STUDY00005069 - Ivermectin and human immunity
https://ovpr-click-prod.ovpr.uga.edu/uga-ovpr/ResourceAdministration/P...
9 of 24
26-Nov-18, 12:07


View: UGA SF: Human Research Participants
Human Research Participants
1.0
Click "Add" to provide a general description of the targeted
participants. See Help text on the right for definition of human subject.
Targeted Population
Targeted
Gender
Age or Age
Range
Total Number /
Range
View Healthy adults from the
General Population
None
18-65
12
Human Subject: A
living individual about
whom an investigator
obtains (1) data
through intervention or
interaction with the
individual or (2)
identifiable private
information.  NOTE: if
you are not sure if your
project involves human
subjects, go back to
the Basic Information
page and request for a
determination of
human subjects
research by answering
"Yes" to the first
question in Section 5.
Samples of targeted
population responses:
(e.g., healthy adults
from the general
population, children
enrolled in an after-
school program,
adolescent females
with scoliosis.)
If the target age is
adults (in Georgia, it is
acceptable to choose
"18+" as the target
age.
The "Total
Number/Range" should
include the anticipated
number of those who
will give consent but
may fail screening (if
research involves pre-
screening participants)
and other reasons for
attrition (e.g.,
withdrawals or
termination by
researchers).
2.0
Identify the inclusion and exclusion criteria.  If there are two or more
targeted populations, identify eligibility criteria for each.
Inclusion Criteria:
Weight over 110 pounds and under 185 pounds.
Exclusion Criteria:
Pregnancy or nursing mothers.
Immunosuppressed individuals.
Hypersensitivity to ivermectin, cellulose, starch, magnesium stearate,
butylated hydroxyanisole, or citric acid powder (inert ingredients of
Stromectol).
Lactose intolerance (Lactose present in placebo)
Recent (last 3 years) travel to West or Central Africa, or any othet country
where onchocerciasis is present
Hepatitis/HIV
Liver or renal dysfunction
Currently taking any of the following medications (potential for drug
interaction):
- Blood thinners such as Coumadin (warfarin) or aspirin
- Steroid medications (inhaled, oral or injection)
- Barbiturates
- Benzodiazepines such as Xanax or Klonopin
It is not necessary to
list exclusion criteria as
the opposite of
inclusion criteria. Use
these fields to narrow
or refine the general
description provided in
Q1.
Print: STUDY00005069 - Ivermectin and human immunity
https://ovpr-click-prod.ovpr.uga.edu/uga-ovpr/ResourceAdministration/P...
10 of 24
26-Nov-18, 12:07


- Valproic acid (Lithium)
- Calcium channel blockers
- Statins (cholesterol medication)
3.0
Describe how potential participants will be initially identified and how
eligibility will be determined.
Self-selection by reviewing recruitment materials; potential participants will
call the CTRU to be screened to determine eligibility. Verbal consent for
screening will be obtained as the first part of the interview.
Possible methods of
identification include
public record review,
private medical or
school record review. 
If individuals will self-
select by reviewing the
eligiblity criteria listed
in the recruitment
materials, state this. 
Or describe the
process for screening
by phone, in-person or
e-mail, or review of
records.
4.0
If the research will exclude a particular gender or minority group,
provide justification.
N/A
When appropriate,
provide citations or
references to support
the justification. 
5.0
Describe any incentive/compensation for participation.
Participants will receive free parking at the CTRU, where blood will be drawn,
and monetary compensation of $25 cash for each time they allow blood to be
drawn, plus $25 for taking the drug, for a total of $100 if all parts of the study
are completed. A light meal will be provided during the first visit to CTRU to
compensate for fasting.
Indicate the form of
incentive/compensation
(e.g., monetary
payment by check, gift
card, services without
charge, reimbursement
for travel cost.)  If
offering extra class
credit, describe the
available non-research
alternative of
comparable time and
effort.
Print: STUDY00005069 - Ivermectin and human immunity
https://ovpr-click-prod.ovpr.uga.edu/uga-ovpr/ResourceAdministration/P...
11 of 24
26-Nov-18, 12:07


View: UGA SF: Vulnerable and/or Special Populations
Vulnerable and/or Special Populations
1.0
Check any/all that apply.
Population:
Pregnant women, neonates, or fetuses.
Prisoners
Minors
Mentally-disabled/cognitively-impaired/severe psychological disorders
Physically-disabled
Terminally ill
Economically/educationally disadvantaged
A specific group based on religion, race, ethnicity, immigration status,
language, or sexual orientation
Students/Employees
Other (please describe)
If you are using a UGA
student research pool
and pool guidelines
require an educational
debriefing, please
attach the debriefing to
the supporting
documents page and
label it "Educational
Debriefing".
2.0
Provide justification for including the group(s) checked above in this
particular study.
It is possible that some of the participants may be students or employees of
the university, possibly within the same department or lab as the investigator.
3.0
Describe the working relationship between any researchers and the
participants, as applicable.
It is possible that some of the participants may be graduate students or work in
the same department as the investigators.
A working relationship
may exist between a
researcher and his/her
own students or
employees.
4.0
Describe the safeguards to protect the rights and welfare of these
participants and to minimize any possible coercion or undue influence.
Minors or those with cognitive impairments will not be included. The amount of
the payment is intended to compensate participants for their time, and not as
an undue inducement to take part. We will attempt to recruit participants who
do not have a working relationship with the investigators.
For example, assess
the amount of payment
and how/if it
will present undue
influence for the
financially
disadvantaged.  For
minors or people with
cognitive impairment
or educational
disadvantage, describe
how you
will ensure participants'
understanding of the
study (e.g., by using
advocatesduring the
consent process). To
mitigate a working
relationship, consider
use flyers to recruit
participants instead of
directly approaching
your own staff or
students.
Print: STUDY00005069 - Ivermectin and human immunity
https://ovpr-click-prod.ovpr.uga.edu/uga-ovpr/ResourceAdministration/P...
12 of 24
26-Nov-18, 12:07


View: UGA SF: Recruitment Methods and Procedures
Recruitment Methods and Materials
1.0
Will you recruit (invite) individuals to take part in your study?
Yes
No
Recruit means to
provide information
about the study and
invite people to take
part. Any study that
involves interaction
with subjects should
have a well-defined
recruitment
process.  If you
answer "yes", you
must submit
materials below.
2.0
Describe when, where, and how participants will be initially contacted.
Study flyer has been uploaded and will be a main method of recruitment. It will
be used in other methods of advertisement include advertising through the CTRU,
posting to websites (including the CTRU website), social media, email
communication including listservs, newspaper ads. Subjects will be invited to call
or email study staff to determine eligibility.
Methods of
recruitment could
include, but are not
limited to: In person,
Phone call, flyers,
brochures, bulletin
boards, letters,
social media, media
advertisements
(e.g., newspaper,
radio, TV
announcements),
research pool
project listing
systems (e.g.,
SONA).
3.0
Describe any follow-up recruitment (e.g. multiple attempts/contacts for
the purpose of inviting someone to participate).
Individuals will only be called more than once for the purpose of inviting them to
participate if they have contacted us requesting more information and have not
been successful at reaching us. Additional attempts to call them may be made if
the first attempt was not successful and the required number of participants has
not been reached.
4.0
Recruitment Materials: (add all to be seen or heard by subjects)
Document
Category
Date Modified
View Study ad edit.docx(0.04)
Recruitment Materials 8/22/2017
View Screening Consent and phone script(5) Recruitment Materials 1/26/2018
Add all materials to
be seen or heard by
subjects. All file
types are supported.
Print: STUDY00005069 - Ivermectin and human immunity
https://ovpr-click-prod.ovpr.uga.edu/uga-ovpr/ResourceAdministration/P...
13 of 24
26-Nov-18, 12:07


View: UGA SF: Consent Process and Materials
Consent Process and Materials
1.0
Select the applicable option(s) below to describe the consent
process/es for this study.
Informed consent will be
obtained and documented
The consent process includes all
elements of consent and participants
will sign a consent document.
Signatures will not be obtained
on consent documents
Participants will not physically sign a
document as part of the consent
process.
Informed consent will not be
obtained or some or all elements
will be waived or altered
There will not be a consent process or the
consent process will not include all
elements of informed consent.
 If there are multiple
consent processes
(for different subject
groups or for
separate phases of
data collection), you
may mark more than
one, as applicable. If
the study involves
deception or
incomplete
disclosure, indicate
that consent will be
waived or altered. 
For data collection
via the Internet,
indicate that
participants will not
sign consent
documents.
2.0
Describe how, where and when informed consent will be
obtained from research participants.
Consent will be obtained for fasting during the screening interview. Signed
informed consent for other aspects of the study will be obtained at the time of
the participant's first visit to CTRU.
Where one or more
processes will be
used (e.g., no
signature for an
online consent but
signed forms for
interviews of some
survey participants),
describe each
process separately. 
If there are discrete
subject groups (e.g.,
minors and adults),
describe each
process (e.g.,
parental permission,
minor assent, adult
consent) separately. 
See Policy and
Procedure: Informed
Consent Process for
Research in the
Library for additional
guidance.
3.0
Consent Forms:
Important Note: The IRB strongly recommends the use of consent templates that are
available on the consent materials page to ensure that all the elements of informed consent
are included (per 45 CFR 116).  If more than one consent document will be used, please
name each accordingly.
Refer to the following templates:
Consent Template - Parental Permission Form
Policy and Procedure: Informed Consent Process for Research
Consent Template - Minor Assent
Consent Template - Consent Form (with signature)
Consent Template - Telephone Eligibility Screening Consent Script
Consent Template - Consent Cover Letter (no signature)
Consent Template - Consent Form for Use of Data Already Collected
(Artifacts)
Attach consent forms below:
Document
Category
Date Modified
View Consent form(7)
Consent Form
2/6/2018
Guidance and
policies and
procedures for
informed consent
can be found in the
IRB Library. _
Print: STUDY00005069 - Ivermectin and human immunity
https://ovpr-click-prod.ovpr.uga.edu/uga-ovpr/ResourceAdministration/P...
14 of 24
26-Nov-18, 12:07


View: UGA SF: Waiver of Requirements to Document Informed Consent
Waiver of Requirements to Document Informed Consent
1.0
The IRB may waive the requirement to obtain a signed consent document
for some or all subjects if it finds that the project meets one of the criteria
below.  Please choose the appropriate criterion.
Criteria 2
2.0
Provide supporting justification for requesting a waiver to document
informed consent.
We are simply asking participants to avoid eating solid food for two hours prior to
the first visit, to ensure reproducible effects of the drug - which is recommended
be given on an empty stomach. This is much less than the fasting required prior
to annual medical exams for example and presents minimal risk.
Print: STUDY00005069 - Ivermectin and human immunity
https://ovpr-click-prod.ovpr.uga.edu/uga-ovpr/ResourceAdministration/P...
15 of 24
26-Nov-18, 12:07


View: UGA SF: Research Design, Methods and Procedures
Research Design, Methods and Procedures
1.0
Brief Description (see Help)
We hypothesize that ivermectin interacts with the human innate immune system
and that this contributes to its anti-parasitic effects. Participants will donate blood
before and after being administered the normal human dose of the drug. We
compare the CBC and cytokine profile of the two samples, and measure any
changes in gene expression in leukocyte populations 4 and 24hrs after the drug
is taken.
Summarize the
overall research
question and the
primary objectives.
If the project does
not involve a
systematic
investigation (e.g.,
biography) or is not
designed to
contribute to
generalizable
knowledge (e.g.,
oral history, quality
assurance), request
for a determination
of human subject
research by
answering "Yes" to
the first question in
Section 5 on the
Basic Information
page (first page of
the submission).
2.0
Research Design and Methods
Describe the overall research design and method(s) of data collection.
Also, identify specific factors or variables and, if applicable, treatment and
control conditions or groups.
Subjects will visit the CTRU twice on consecutive days and blood will be drawn
from them. On the first occasion they will be weighed and will complete the
consent process. They will have been randomly assigned to the test (Stromectol)
or control (placebo) group, with 8 participants in the test group and 4
participants in the control group. Stromectol will be obtained from a medical
supply distributor and a placebo will be obtained through the UGA School of
Pharmacy. Drugs will be prescribed by Jonathan Murrow MD. They will be stored
in their original packaging at room temperature in a drug locker in the lab at
CTRU. Participants will be identified by number and allocated to groups using a
block randomization protocol. Randomization and drug dispensation will be done
by CTRU. 18ml of blood will drawn in a fasting state and they will be
administered 150 mcg/kg Stromectol or the equivalent number of placebo tablets
immediately after blood is drawn. Participants will remain at CTRU for four hours
after they take the drug, then another 15ml of blood will be drawn. On the
second day they will attend CTRU at the same time and the third blood sample
(18ml) will be drawn 24 hrs after administration of the drug. On each occasion
the drawn blood will be coded by CTRU staff prior to being collected by a member
of the Department of Infectious Diseases and taken to the laboratory (Wildlife
Health G0007) for the isolation of leukocyte populations (peripheral monocytes,
lymphocytes and polymorphonuclear cells (PMNs)) and for the preparation of
serum. Complete blood counts will also be carried out. Sera will be analyzed on
the Luminex for cytokine/chemokine content. RNA will be isolated from the cell
populations for RNASeq analysis.
If groups or
conditions will be
assigned, specify
the number of
research
participants that will
be assigned to each
condition or group.
3.0
Duration of Participation and Study Timeline
Describe the time commitment per activity per individual subject and
provide the estimated total duration of participation.  If known, also
describe the anticipated duration to enroll all study subjects and the
estimated time until completion of primary analyses.
Subjects will visit the CTRU twice in two days. On the first visit, they will have
fasted for at least two hours. They will be asked to sign the consent form and will
be weighed. They will donate blood, then take Stromectol at a dose of
150mcg/kg, or the placebo. After taking the drug, they will remain at the CTRU
for four hours, then another blood sample will be drawn. On the second day they
will attend CTRU at the same time (24 hrs after the first visit), when they will
again donate blood. The first visit should last about 5 hrs and the second visit
less than 1 hr.
4.0
Procedures
Describe in detail, and in sequence, all study procedures from the
Practice is the
exercise of an
Print: STUDY00005069 - Ivermectin and human immunity
https://ovpr-click-prod.ovpr.uga.edu/uga-ovpr/ResourceAdministration/P...
16 of 24
26-Nov-18, 12:07


perspective of the participant.  Begin with any procedure that involves
interaction or collection of data to determine eligibility, if applicable. 
Separate any procedures that are part of regular practice from procedures
that are specific to this research study.  If procedures are long and
complicated, use a table, flowchart or diagram to outline the study
procedures.
Participants will respond to an invitation to take part, either by phone or by
responding to a posted flyer. After the screening interview, they will visit the
CTRU two times within a 1-week period. They will receive a reminder with fasting
instructions prior to their first visit. On the first visit, they will complete and sign
the consent form and be weighed. They will then undergo a blood draw and then
will take 3 or 4 tablets of Stromectol (ivermectin), depending on their weight.
They will stay at the CTRU for the next four hours, and then another blood draw
will be performed. On the second visit the following day, another blood draw will
be performed. After this, or after they voluntarily withdraw from the study, they
will receive $25 in cash for each blood sample they have donated, and $25 cash
for taking the drug.
occupation or a
profession; activities
that are part of
"practice" are
conducted with all
members of a
population whether
or not they consent
to participate in
research.
Research activities
are voluntary, must
follow a documented
protocol, and are
conducted under
specific conditions in
order to draw
generalizable
conclusions.
A project may use a
combination of
practice and
research in order
to reach desired
objectives. 
5.0
Data Analysis
Describe the data analysis plan, including any statistical procedures.  For
qualitative studies, specify the proposed analytic approaches.
Differences between the samples taken from individual participants will be
assessed via ANOVA. Data will be stored on the principal investigator's computer,
anonymously. RNASeq data will be deposited in a relevant database, as required
by most journals and funding agencies; this will not be able to be linked to any
study participant. RNASeq data will be analyzed using DESEQ2 or similar method
to identify transcripts that are significantly altered in participants receiving the
drug but not the placebo.
If data or specimens
will be banked for
future use, describe
where/how these will
be stored and
accessed and how
they may be
used/analyzed. If
analysis will be
conducted by
investigators outside
UGA, be sure to
include these sites
and investigators in
the corresponding
submission forms.
Print: STUDY00005069 - Ivermectin and human immunity
https://ovpr-click-prod.ovpr.uga.edu/uga-ovpr/ResourceAdministration/P...
17 of 24
26-Nov-18, 12:07


View: UGA SF: Data Collection Instruments and Measures
Data Collection Materials
1.0
Click "Add" to list, describe, and attach all the materials that will be used to collect and
record data/information for this study.   
Instrument
Name
Instrument
Description
Participant Groups
who will Complete
Attachment
View Data
Spreadsheet
Record of CBC,
Luminex and
parasite killing data
Drs Reaves &
Wolstenholme
data to be
recorded.xlsx(0.01)
Data Collection
Materials may
include, but are not
limited to: surveys,
interview
guides/questions,
questionnaires,
focus group
guides/questions,
observation guides,
bio-metric measure
recording sheets. 
Do not list
equipment such as
audio/video-
recording devices,
EKG, Ultrasound.
Print: STUDY00005069 - Ivermectin and human immunity
https://ovpr-click-prod.ovpr.uga.edu/uga-ovpr/ResourceAdministration/P...
18 of 24
26-Nov-18, 12:07


View: UGA SF: Risks and Benefits
Risks and Benefits
1.0
If there is collection of information that could place a participant at risk of
criminal or civil liability or damage a participant's financial standing,
employability, or reputation, mark any box(es) that apply below.  If
information to be collected is not sensitive, do not mark any.  The list
below is not exhaustive but represents common elements or procedures
in research where the primary risk is potential harm associated with
breach of confidentiality.
There are no items to display
If the study includes
collection
of identifiable
sensitive information
(e.g., mental or
physical health,
drug/alcohol use,
sexual identity or
behaviors, religious
beliefs or practices),
then a breach of
confidentiality may
be the primary risk
for participants.
2.0
Describe in detail the nature and degree of risk and discomfort associated
with participation.  Address any items marked above in detail.  Include
any foreseeable physical risks, psychological harm, and/or privacy
concerns that are associated with the procedures/interventions (See
HELP on right.).
The risks of drawing blood from the arm include the possibilities of a small bruise, infection,
bleeding or lightheadedness/fainting.
In controlled clinical trials, the following laboratory adverse experiences were reported as
possibly, probably, or definitely related to ivermectin in ≥1% of the patients: eosinophilia (3%)
and hemoglobin increase (1%). The following adverse reactions have been reported since
ivermectin was registered overseas: Hypotension (mainly orthostatic hypotension), worsening
of bronchial asthma, toxic epidermal necrolysis, Stevens-Johnson syndrome, seizures,
hepatitis, elevation of liver enzymes, and elevation of bilirubin.
The Mazzotti-type and ophthalmologic reactions associated with the treatment of
onchocerciasis or the disease itself would not be expected to occur in uninfected people; this
disease is not endemic to the USA.
Assess risk and
discomfort
associated with all
study procedures
including access to
and use of
identifiable
information or
specimens. 
Consider the
procedures
described on the
Research Design,
Methods and
Procedures page,
the recruitment
process, and the
study consent
process when
assessing privacy
concerns.
3.0
Describe the measures that will be taken to minimize each of the potential
risks and discomforts identified in questions 1 and 2.
Nurses at the CTRU are well trained in sterile venipuncture procedure and care is taken to
minimize bruising, fainting and other adverse incidents related to venipuncture. Participants
will remain at the CTRU for four hours after taking the drug, which will allow monitoring of any
unforeseen adverse events.
Measures to mitigate
risk associated with
breach of
confidentiality (if any
are identified in Q1)
include limiting
collection and/or
retention of
identifers provided
with data, or using
coding procedures
to replace direct
identifiers with
codes/pseudonyms. 
Lab safety protocols,
appropriate eligibility
criteria, and
monitoring for
safety may
be measures to
mitigate physical
and psychological
risk. Privacy
concerns can be
addressed by
allowing people to
control the nature of
information they
give, the time and
place where study
procedures take
place, the things
they are required to
do, and who has
access to their
identifiable
inforamation.  For
Print: STUDY00005069 - Ivermectin and human immunity
https://ovpr-click-prod.ovpr.uga.edu/uga-ovpr/ResourceAdministration/P...
19 of 24
26-Nov-18, 12:07


example, people
may want to be
weighed in a private
location.
4.0
Describe any anticipated direct benefits to participants.  If there are none,
please state so.
None
5.0
Describe any anticipated benefits to others (e.g., societal) that may result
from the research. Describe the generalizable or transferable knowledge
that may result.
Ivermectin is a crucially important drug in programs to globally eliminate human
filarial diseases. A better understanding of how it interacts with the human innate
immune system may aid in the design and implementation of those programs, or
lead to novel approaches to the development of new treatments to improve their
efficacy.
The IRB must
determine that
benefits outweigh
risks in order to
approve research.  If
there is no or little
risk, there can be
fewer anticipated
benefits.This
response must
match the study
consent document, if
applicable.
Print: STUDY00005069 - Ivermectin and human immunity
https://ovpr-click-prod.ovpr.uga.edu/uga-ovpr/ResourceAdministration/P...
20 of 24
26-Nov-18, 12:07


View: UGA SF: Confidentiality and Privacy
Confidentiality and Privacy
1.0
Will the researchers collect or record any direct identifiers with the data
(e.g., names, addresses, telephone numbers)?
No. Skip to Q5
Yes. Complete Q2-4
If the research
activities are limited
to analysis of de-
identified datasets
or specimens,
request for a
determination of
human subject
research by
answering "Yes" to
the first question in
Section 5 on the
Basic Information
Page (the first page
of the submission.)
For no risk studies
or studies where
sensitive information
are not obtained, it
is acceptable to use
direct identifiers.
However, if there
is potential risk
associated with a
breach of
confidentiality,
consider utilizing a
coding procedure to
replace direct
identifiers with
codes or unique
study IDs.
2.0
Indicate which of the direct identifiers below will be collected or included
with the data:
Audio-Recordings of Participants
Postal Address
Email Addresses
Videos of Participants
Telephone Numbers
Photographs of participant in which he/she is identifiable
Full Names
3.0
Will the researchers retain direct identifiers after data collection is
complete?
Yes
No
4.0
If the answer to Q3 is yes, why is it necessary to retain direct identifiers
after completion of data collection?
5.0
Will the researchers use a coding system and/or will the data be
collected via the Internet?
Yes
No
Data collection
methods via the
Internet include, but
are not limited to:
online data
collection host/tool
such as Qualtrics or
SurveyMonkey,
social media.
websites. 
6.0
Describe the coding system that will be used to link the code
(pseudonym or study ID) to the participant (e.g., code key or master list).
If data are collected via the Internet, describe what indirect identifiers
may be collected (e.g., IP addresses).
A random code will be allocated to each participant by the CTRU, but this
system will not be divulged to the investigators. Each sample will have a
randomly generated numerical code. At the end of the study, the sample
numbers corresponding to each participant, but not the participants' identity,
Many Internet
hosts/tools offer a
way for investigators
to have IP
addresses stripped
before data are
downloaded by the
researcher.  If this is
Print: STUDY00005069 - Ivermectin and human immunity
https://ovpr-click-prod.ovpr.uga.edu/uga-ovpr/ResourceAdministration/P...
21 of 24
26-Nov-18, 12:07


will be revealed to the investigators.
available, the IRB
suggests using such
tools.  If this is not
available, or not
utlized, be sure to
acknowledge that IP
addresses may be
included in the data
and provide
resonses to Q7-9.
7.0
If a coding system is used or data are collected via the Internet, will the
link/indirect identifier be retained after data collection is complete?
Yes
No
8.0
If the answer ty Q7 is yes, why is it necessary to retain the link/indirect
identifier?
Common reasons to
retain a link include
but are not limited
to: multiple data
sources, data
collected over
multiple timepoints.
9.0
Describe how long the direct/indirect identifiers or the link will be
retained, where and how this information will be stored, and what
security provisions will be taken to protect the data.  If information
that associates a person with his/her data will be retained after data
collection is complete, all potential uses of this information must be
described here and in the consent documents.
No direct identifiers will be collected with the data, only to generate study IDs
and send reminders. The link between identifiable information and study IDs will
be retained only long enough for data collection. This link will be kept password-
protected on secure servers, only accessible by CTRU staff.
 If there is risk
associated with a
breach of
confidentiality, the
IRB recommends
that direct identifiers
or links between the
participant and
his/her data be
destroyed at the
earliest point
possible congruent
with the research
design and plans for
analysis.  Note: For
non-Exempt
research, if the
study involves
minors and
identifiable data will
continue to be
used/analyzed after
the minor becomes
an adult (18 in
Georgia), consent
must be obtained
from the now-adult
participant even if
parental permission
and assent were
previously obtained.
10.0
Is it reasonable foreseeable that the study will collect or be privy to
information that State or Federal law requires to be reported to other
officials (e.g., child or elder abuse) or ethically might require action by
the research (e.g., suicidal ideation, intent to hurt self or others)?  If
"Yes", this must be described in the the consent documents.
Yes
No
If the investigator
does not have a
mandate to report
such
information, but the
investigator will
voluntarily breach
confidentiality to
report such matters,
this must be
declared here and in
the study consent
documents.
Print: STUDY00005069 - Ivermectin and human immunity
https://ovpr-click-prod.ovpr.uga.edu/uga-ovpr/ResourceAdministration/P...
22 of 24
26-Nov-18, 12:07


View: UGA SF: Supporting Documents
Supporting Documents
1.0
Attach supporting documents and any other study-related materials
not specifically requested on previous sections.
Document
Category
Date Modified
View Fasting Instructions for Participants.docx(1)
Other
9/14/2017
Print: STUDY00005069 - Ivermectin and human immunity
https://ovpr-click-prod.ovpr.uga.edu/uga-ovpr/ResourceAdministration/P...
23 of 24
26-Nov-18, 12:07


View: SF: Final Page
Final Page
You have reached the end of the IRB submission form. When you are ready to submit to the IRB, follow  the next steps
carefully:
Click Hide/Show Errors to check for missing information. Address any errors.
1. 
 Click Finish to exit the form.
2. 
Important! If you are the PI, click Submit on the next page.  If you are not the PI, click Notify PI to
Submit to send an e-mail to the PI indicating that the submission is ready to send to the IRB.
3. 
Print: STUDY00005069 - Ivermectin and human immunity
https://ovpr-click-prod.ovpr.uga.edu/uga-ovpr/ResourceAdministration/P...
24 of 24
26-Nov-18, 12:07


 
9032319
87447/080610
8495
 
1 
TABLETS 
STROMECTOL® 
(IVERMECTIN) 
 
DESCRIPTION 
STROMECTOL* (Ivermectin) is a semisynthetic, anthelmintic agent for oral administration. Ivermectin 
is derived from the avermectins, a class of highly active broad-spectrum, anti-parasitic agents isolated 
from the fermentation products of Streptomyces avermitilis. Ivermectin is a mixture containing at least 
90% 5-O-demethyl-22,23-dihydroavermectin A1a and less than 10% 5-O-demethyl-25-de(1-methylpropyl)-
22,23-dihydro-25-(1-methylethyl)avermectin A1a, generally referred to as 22,23-dihydroavermectin B1a 
and B1b, or H2B1a and H2B1b, respectively. The respective empirical formulas are C48H74O14 and 
C47H72O14, with molecular weights of 875.10 and 861.07, respectively. The structural formulas are: 
 
 
 
 
 
 
Component B1a, R = C2H5 
 
Component B1b, R = CH3 
 
Ivermectin is a white to yellowish-white, nonhygroscopic, crystalline powder with a melting point of 
about 155°C. It is insoluble in water but is freely soluble in methanol and soluble in 95% ethanol. 
STROMECTOL is available in 3-mg tablets containing the following inactive ingredients: 
microcrystalline cellulose, pregelatinized starch, magnesium stearate, butylated hydroxyanisole, and citric 
acid powder (anhydrous). 
CLINICAL PHARMACOLOGY 
Pharmacokinetics 
Following oral administration of ivermectin, plasma concentrations are approximately proportional to 
the dose. In two studies, after single 12-mg doses of STROMECTOL in fasting healthy volunteers 
(representing a mean dose of 165 mcg/kg), the mean peak plasma concentrations of the major 
component (H2B1a) were 46.6 (±21.9) (range: 16.4-101.1) and 30.6 (±15.6) (range: 13.9-68.4) ng/mL, 
respectively, at approximately 4 hours after dosing. Ivermectin is metabolized in the liver, and ivermectin 
and/or its metabolites are excreted almost exclusively in the feces over an estimated 12 days, with less 
than 1% of the administered dose excreted in the urine. The plasma half-life of ivermectin in man is 
approximately 18 hours following oral administration. 
The safety and pharmacokinetic properties of ivermectin were further assessed in a multiple-dose 
clinical pharmacokinetic study involving healthy volunteers. Subjects received oral doses of 30 to 120 mg 
(333 to 2000 mcg/kg) ivermectin in a fasted state or 30 mg (333 to 600 mcg/kg) ivermectin following a 
standard high-fat (48.6 g of fat) meal. Administration of 30 mg ivermectin following a high-fat meal 
resulted in an approximate 2.5-fold increase in bioavailability relative to administration of 30 mg 
ivermectin in the fasted state. 
                                                                          
 
* Registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. 
 Copyright © 1996, 2007 Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. 
 All rights reserved 


STROMECTOL® (Ivermectin) 
9032319 
87447/080610 
8495 
2 
In vitro studies using human liver microsomes and recombinant CYP450 enzymes have shown that 
ivermectin is primarily metabolized by CYP3A4. Depending on the in vitro method used, CYP2D6 and 
CYP2E1 were also shown to be involved in the metabolism of ivermectin but to a significantly lower 
extent compared to CYP3A4. The findings of in vitro studies using human liver microsomes suggest that 
clinically relevant concentrations of ivermectin do not significantly inhibit the metabolizing activities of 
CYP3A4, CYP2D6, CYP2C9, CYP1A2, and CYP2E1. 
 
Microbiology 
Ivermectin is a member of the avermectin class of broad-spectrum antiparasitic agents which have a 
unique mode of action. Compounds of the class bind selectively and with high affinity to glutamate-gated 
chloride ion channels which occur in invertebrate nerve and muscle cells. This leads to an increase in the 
permeability of the cell membrane to chloride ions with hyperpolarization of the nerve or muscle cell, 
resulting in paralysis and death of the parasite. Compounds of this class may also interact with other 
ligand-gated chloride channels, such as those gated by the neurotransmitter gamma-aminobutyric acid 
(GABA). 
The selective activity of compounds of this class is attributable to the facts that some mammals do not 
have glutamate-gated chloride channels and that the avermectins have a low affinity for mammalian 
ligand-gated chloride channels. In addition, ivermectin does not readily cross the blood-brain barrier in 
humans. 
Ivermectin is active against various life-cycle stages of many but not all nematodes. It is active against 
the tissue microfilariae of Onchocerca volvulus but not against the adult form. Its activity against 
Strongyloides stercoralis is limited to the intestinal stages. 
Clinical Studies 
Strongyloidiasis 
Two controlled clinical studies using albendazole as the comparative agent were carried out in 
international sites where albendazole is approved for the treatment of strongyloidiasis of the 
gastrointestinal tract, and three controlled studies were carried out in the U.S. and internationally using 
thiabendazole as the comparative agent. Efficacy, as measured by cure rate, was defined as the absence 
of larvae in at least two follow-up stool examinations 3 to 4 weeks post-therapy. Based on this criterion, 
efficacy was significantly greater for STROMECTOL (a single dose of 170 to 200 mcg/kg) than for 
albendazole (200 mg b.i.d. for 3 days). STROMECTOL administered as a single dose of 200 mcg/kg for 
1 day was as efficacious as thiabendazole administered at 25 mg/kg b.i.d. for 3 days. 
 
Summary of Cure Rates for Ivermectin Versus Comparative Agents in the  
Treatment of Strongyloidiasis 
 
  
Cure Rate* (%) 
  
Ivermectin** 
Comparative Agent 
Albendazole*** Comparative 
International Study 
WHO Study 
 
24/26 (92) 
126/152 (83) 
 
12/22 (55) 
67/149 (45) 
Thiabendazole† Comparative 
International Study 
US Studies 
 
9/14 (64) 
14/14 (100) 
 
13/15 (87) 
16/17 (94) 
  
* 
Number and % of evaluable patients 
** 
170-200 mcg/kg 
*** 
200 mg b.i.d. for 3 days 
† 
25 mg/kg b.i.d. for 3 days 
 
In one study conducted in France, a non-endemic area where there was no possibility of reinfection, 
several patients were observed to have recrudescence of Strongyloides larvae in their stool as long as 
106 days following ivermectin therapy. Therefore, at least three stool examinations should be conducted 
over the three months following treatment to ensure eradication. If recrudescence of larvae is observed, 
retreatment with ivermectin is indicated. Concentration techniques (such as using a Baermann 
apparatus) should be employed when performing these stool examinations, as the number of 
Strongyloides larvae per gram of feces may be very low. 


STROMECTOL® (Ivermectin) 
9032319 
87447/080610 
8495 
3 
Onchocerciasis 
The evaluation of STROMECTOL in the treatment of onchocerciasis is based on the results of clinical 
studies involving 1278 patients. In a double-blind, placebo-controlled study involving adult patients with 
moderate to severe onchocercal infection, patients who received a single dose of 150 mcg/kg 
STROMECTOL experienced an 83.2% and 99.5% decrease in skin microfilariae count (geometric mean) 
3 days and 3 months after the dose, respectively. A marked reduction of >90% was maintained for up to 
12 months after the single dose. As with other microfilaricidal drugs, there was an increase in the 
microfilariae count in the anterior chamber of the eye at day 3 after treatment in some patients. However, 
at 3 and 6 months after the dose, a significantly greater percentage of patients treated with 
STROMECTOL had decreases in microfilariae count in the anterior chamber than patients treated with 
placebo. 
In a separate open study involving pediatric patients ages 6 to 13 (n=103; weight range: 17-41 kg), 
similar decreases in skin microfilariae counts were observed for up to 12 months after dosing. 
INDICATIONS AND USAGE 
STROMECTOL is indicated for the treatment of the following infections: 
Strongyloidiasis of the intestinal tract. STROMECTOL is indicated for the treatment of intestinal 
(i.e., nondisseminated) strongyloidiasis due to the nematode parasite Strongyloides stercoralis. 
This indication is based on clinical studies of both comparative and open-label designs, in which 
64-100% of infected patients were cured following a single 200-mcg/kg dose of ivermectin. (See 
CLINICAL PHARMACOLOGY, Clinical Studies.)  
 
 
Onchocerciasis. STROMECTOL is indicated for the treatment of onchocerciasis due to the 
nematode parasite Onchocerca volvulus. 
This indication is based on randomized, double-blind, placebo-controlled and comparative studies 
conducted in 1427 patients in onchocerciasis-endemic areas of West Africa. The comparative studies 
used diethylcarbamazine citrate (DEC-C). 
NOTE: STROMECTOL has no activity against adult Onchocerca volvulus parasites. The adult 
parasites reside in subcutaneous nodules which are infrequently palpable. Surgical excision of these 
nodules (nodulectomy) may be considered in the management of patients with onchocerciasis, since this 
procedure will eliminate the microfilariae-producing adult parasites. 
CONTRAINDICATIONS 
STROMECTOL is contraindicated in patients who are hypersensitive to any component of this 
product. 
WARNINGS 
Historical data have shown that microfilaricidal drugs, such as diethylcarbamazine citrate (DEC-C), 
might cause cutaneous and/or systemic reactions of varying severity (the Mazzotti reaction) and 
ophthalmological reactions in patients with onchocerciasis. These reactions are probably due to allergic 
and inflammatory responses to the death of microfilariae. Patients treated with STROMECTOL for 
onchocerciasis may experience these reactions in addition to clinical adverse reactions possibly, 
probably, or definitely related to the drug itself. (See ADVERSE REACTIONS, Onchocerciasis.) 
The treatment of severe Mazzotti reactions has not been subjected to controlled clinical trials. Oral 
hydration, recumbency, intravenous normal saline, and/or parenteral corticosteroids have been used to 
treat postural hypotension. Antihistamines and/or aspirin have been used for most mild to moderate 
cases. 
PRECAUTIONS 
General 
After treatment with microfilaricidal drugs, patients with hyperreactive onchodermatitis (sowda) may be 
more likely than others to experience severe adverse reactions, especially edema and aggravation of 
onchodermatitis. 


STROMECTOL® (Ivermectin) 
9032319 
87447/080610 
8495 
4 
Rarely, patients with onchocerciasis who are also heavily infected with Loa loa may develop a serious 
or even fatal encephalopathy either spontaneously or following treatment with an effective microfilaricide. 
In these patients, the following adverse experiences have also been reported: pain (including neck and 
back pain), red eye, conjunctival hemorrhage, dyspnea, urinary and/or fecal incontinence, difficulty in 
standing/walking, mental status changes, confusion, lethargy, stupor, seizures, or coma. This syndrome 
has been seen very rarely following the use of ivermectin. In individuals who warrant treatment with 
ivermectin for any reason and have had significant exposure to Loa loa-endemic areas of West or Central 
Africa, pretreatment assessment for loiasis and careful post-treatment follow-up should be implemented. 
Information for Patients 
STROMECTOL 
should 
be 
taken 
on 
an 
empty 
stomach 
with 
water. 
(See 
CLINICAL 
PHARMACOLOGY, Pharmacokinetics.) 
Strongyloidiasis: The patient should be reminded of the need for repeated stool examinations to 
document clearance of infection with Strongyloides stercoralis. 
Onchocerciasis: The patient should be reminded that treatment with STROMECTOL does not kill the 
adult Onchocerca parasites, and therefore repeated follow-up and retreatment is usually required. 
Drug Interactions 
Post-marketing reports of increased INR (International Normalized Ratio) have been rarely reported 
when ivermectin was co-administered with warfarin. 
Carcinogenesis, Mutagenesis, Impairment of Fertility 
Long-term studies in animals have not been performed to evaluate the carcinogenic potential of 
ivermectin. 
Ivermectin was not genotoxic in vitro in the Ames microbial mutagenicity assay of Salmonella 
typhimurium strains TA1535, TA1537, TA98, and TA100 with and without rat liver enzyme activation, the 
Mouse Lymphoma Cell Line L5178Y (cytotoxicity and mutagenicity) assays, or the unscheduled DNA 
synthesis assay in human fibroblasts. 
Ivermectin had no adverse effects on the fertility in rats in studies at repeated doses of up to 3 times 
the maximum recommended human dose of 200 mcg/kg (on a mg/m2/day basis). 
Pregnancy, Teratogenic Effects 
Pregnancy Category C 
Ivermectin has been shown to be teratogenic in mice, rats, and rabbits when given in repeated doses 
of 0.2, 8.1, and 4.5 times the maximum recommended human dose, respectively (on a mg/m2/day basis). 
Teratogenicity was characterized in the three species tested by cleft palate; clubbed forepaws were 
additionally observed in rabbits. These developmental effects were found only at or near doses that were 
maternotoxic to the pregnant female. Therefore, ivermectin does not appear to be selectively fetotoxic to 
the developing fetus. There are, however, no adequate and well-controlled studies in pregnant women. 
Ivermectin should not be used during pregnancy since safety in pregnancy has not been established. 
Nursing Mothers 
STROMECTOL is excreted in human milk in low concentrations. Treatment of mothers who intend to 
breast-feed should only be undertaken when the risk of delayed treatment to the mother outweighs the 
possible risk to the newborn. 
Pediatric Use 
Safety and effectiveness in pediatric patients weighing less than 15 kg have not been established. 
Geriatric Use 
Clinical studies of STROMECTOL did not include sufficient numbers of subjects aged 65 and over to 
determine whether they respond differently from younger subjects. Other reported clinical experience has 
not identified differences in responses between the elderly and younger patients. In general, treatment of 
an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or 
cardiac function, and of concomitant disease or other drug therapy. 
Strongyloidiasis in Immunocompromised Hosts 
In immunocompromised (including HIV-infected) patients being treated for intestinal strongyloidiasis, 
repeated courses of therapy may be required. Adequate and well-controlled clinical studies have not 
been conducted in such patients to determine the optimal dosing regimen. Several treatments, i.e., at 2-
week intervals, may be required, and cure may not be achievable. Control of extra-intestinal 
strongyloidiasis in these patients is difficult, and suppressive therapy, i.e., once per month, may be 
helpful. 


STROMECTOL® (Ivermectin) 
9032319 
87447/080610 
8495 
5 
ADVERSE REACTIONS 
Strongyloidiasis 
In four clinical studies involving a total of 109 patients given either one or two doses of 170 to 
200 mcg/kg of STROMECTOL, the following adverse reactions were reported as possibly, probably, or 
definitely related to STROMECTOL:  
Body as a Whole: asthenia/fatigue (0.9%), abdominal pain (0.9%) 
Gastrointestinal: anorexia (0.9%), constipation (0.9%), diarrhea (1.8%), nausea (1.8%), vomiting 
(0.9%) 
Nervous System/Psychiatric: dizziness (2.8%), somnolence (0.9%), vertigo (0.9%), tremor (0.9%) 
Skin: pruritus (2.8%), rash (0.9%), and urticaria (0.9%). 
In comparative trials, patients treated with STROMECTOL experienced more abdominal distention 
and chest discomfort than patients treated with albendazole. However, STROMECTOL was better 
tolerated than thiabendazole in comparative studies involving 37 patients treated with thiabendazole. 
The Mazzotti-type and ophthalmologic reactions associated with the treatment of onchocerciasis or 
the disease itself would not be expected to occur in strongyloidiasis patients treated with STROMECTOL. 
(See ADVERSE REACTIONS, Onchocerciasis.) 
Laboratory Test Findings 
In clinical trials involving 109 patients given either one or two doses of 170 to 200 mcg/kg 
STROMECTOL, the following laboratory abnormalities were seen regardless of drug relationship: 
elevation in ALT and/or AST (2%), decrease in leukocyte count (3%). Leukopenia and anemia were seen 
in one patient. 
Onchocerciasis 
In clinical trials involving 963 adult patients treated with 100 to 200 mcg/kg STROMECTOL, worsening 
of the following Mazzotti reactions during the first 4 days post-treatment were reported: 
arthralgia/synovitis (9.3%), axillary lymph node enlargement and tenderness (11.0% and 4.4%, 
respectively), cervical lymph node enlargement and tenderness (5.3% and 1.2%, respectively), inguinal 
lymph node enlargement and tenderness (12.6% and 13.9%, respectively), other lymph node 
enlargement and tenderness (3.0% and 1.9%, respectively), pruritus (27.5%), skin involvement including 
edema, papular and pustular or frank urticarial rash (22.7%), and fever (22.6%). (See WARNINGS.) 
In clinical trials, ophthalmological conditions were examined in 963 adult patients before treatment, at 
day 3, and months 3 and 6 after treatment with 100 to 200 mcg/kg STROMECTOL. Changes observed 
were primarily deterioration from baseline 3 days post-treatment. Most changes either returned to 
baseline condition or improved over baseline severity at the month 3 and 6 visits. The percentages of 
patients with worsening of the following conditions at day 3, month 3 and 6, respectively, were: limbitis: 
5.5%, 4.8%, and 3.5% and punctate opacity: 1.8%, 1.8%, and 1.4%. The corresponding percentages for 
patients treated with placebo were: limbitis: 6.2%, 9.9%, and 9.4% and punctate opacity: 2.0%, 6.4%, and 
7.2%. (See WARNINGS.) 
In clinical trials involving 963 adult patients who received 100 to 200 mcg/kg STROMECTOL, the 
following clinical adverse reactions were reported as possibly, probably, or definitely related to the drug in 
≥1% of the patients: facial edema (1.2%), peripheral edema (3.2%), orthostatic hypotension (1.1%), and 
tachycardia (3.5%). Drug-related headache and myalgia occurred in <1% of patients (0.2% and 0.4%, 
respectively). However, these were the most common adverse experiences reported overall during these 
trials regardless of causality (22.3% and 19.7%, respectively). 
A similar safety profile was observed in an open study in pediatric patients ages 6 to 13. 
The following ophthalmological side effects do occur due to the disease itself but have also been 
reported after treatment with STROMECTOL: abnormal sensation in the eyes, eyelid edema, anterior 
uveitis, conjunctivitis, limbitis, keratitis, and chorioretinitis or choroiditis. These have rarely been severe or 
associated with loss of vision and have generally resolved without corticosteroid treatment. 
Laboratory Test Findings 
In controlled clinical trials, the following laboratory adverse experiences were reported as possibly, 
probably, or definitely related to the drug in ≥1% of the patients: eosinophilia (3%) and hemoglobin 
increase (1%). 
Post-Marketing Experience 
The following adverse reactions have been reported since the drug was registered overseas: 


STROMECTOL® (Ivermectin) 
9032319 
87447/080610 
8495 
6 
Onchocerciasis 
Conjunctival hemorrhage 
All Indications 
Hypotension (mainly orthostatic hypotension), worsening of bronchial asthma, toxic epidermal 
necrolysis, Stevens-Johnson syndrome, seizures, hepatitis, elevation of liver enzymes, and elevation of 
bilirubin. 
OVERDOSAGE 
Significant lethality was observed in mice and rats after single oral doses of 25 to 50 mg/kg and 40 to 
50 mg/kg, respectively. No significant lethality was observed in dogs after single oral doses of up to 
10 mg/kg. At these doses, the treatment-related signs that were observed in these animals include ataxia, 
bradypnea, tremors, ptosis, decreased activity, emesis, and mydriasis. 
In accidental intoxication with, or significant exposure to, unknown quantities of veterinary formulations 
of ivermectin in humans, either by ingestion, inhalation, injection, or exposure to body surfaces, the 
following adverse effects have been reported most frequently: rash, edema, headache, dizziness, 
asthenia, nausea, vomiting, and diarrhea. Other adverse effects that have been reported include: seizure, 
ataxia, dyspnea, abdominal pain, paresthesia, urticaria, and contact dermatitis. 
In case of accidental poisoning, supportive therapy, if indicated, should include parenteral fluids and 
electrolytes, respiratory support (oxygen and mechanical ventilation if necessary) and pressor agents if 
clinically significant hypotension is present. Induction of emesis and/or gastric lavage as soon as 
possible, followed by purgatives and other routine anti-poison measures, may be indicated if needed to 
prevent absorption of ingested material. 
DOSAGE AND ADMINISTRATION 
Strongyloidiasis 
The recommended dosage of STROMECTOL for the treatment of strongyloidiasis is a single oral dose 
designed to provide approximately 200 mcg of ivermectin per kg of body weight. See Table 1 for dosage 
guidelines. Patients should take tablets on an empty stomach with water. (See CLINICAL 
PHARMACOLOGY, Pharmacokinetics.) In general, additional doses are not necessary. However, follow-
up stool examinations should be performed to verify eradication of infection. (See CLINICAL 
PHARMACOLOGY, Clinical Studies.) 
  
Table 1 
Dosage Guidelines for STROMECTOL for Strongyloidiasis 
 
 
Body Weight (kg) 
Single Oral Dose 
 
Number of 3-mg Tablets 
15-24 
1 tablet 
25-35 
2 tablets 
36-50 
3 tablets 
51-65 
4 tablets 
66-79 
5 tablets 
≥80 
200 mcg/kg 
 
Onchocerciasis 
The recommended dosage of STROMECTOL for the treatment of onchocerciasis is a single oral dose 
designed to provide approximately 150 mcg of ivermectin per kg of body weight. See Table 2 for dosage 
guidelines. Patients should take tablets on an empty stomach with water. (See CLINICAL 
PHARMACOLOGY, Pharmacokinetics.) In mass distribution campaigns in international treatment 
programs, the most commonly used dose interval is 12 months. For the treatment of individual patients, 
retreatment may be considered at intervals as short as 3 months. 
  


STROMECTOL® (Ivermectin) 
9032319 
87447/080610 
8495 
7 
Table 2 
Dosage Guidelines for STROMECTOL for Onchocerciasis 
 
 
Body Weight (kg) 
Single Oral Dose 
 
Number of 3-mg Tablets 
15-25 
1 tablet 
26-44 
2 tablets 
45-64 
3 tablets 
65-84 
4 tablets 
≥85 
150 mcg/kg 
 
HOW SUPPLIED 
No. 8495 — Tablets STROMECTOL 3 mg are white, round, flat, bevel-edged tablets coded MSD on 
one side and 32 on the other side. They are supplied as follows: 
NDC 0006-0032-20 unit dose packages of 20. 
Storage 
Store at temperatures below 30°C (86°F). 
 
 
 
Manufactured by: 
Merck Sharp & Dohme BV 
Waarderweg 39 
2031 BN Haarlem 
Netherlands 
 
Issued May 2010 
Printed in the Netherlands 


Research Participants Needed! 
 
Researchers at the University of Georgia are conducting a study on how 
an important drug, ivermectin, might interact with the human immune 
system. The drug is used to treat infections with parasitic nematodes 
(roundworms) 
Participants should: 
- Be between the ages of 18-65 years old; 
- Be healthy and weigh more than 110 lbs, but less than 186 lbs. 
- Not be pregnant or breastfeeding 
- Not have travelled to West or Central Africa in the past 3 years 
- Not be immunosuppressed 
- Live in the Athens area or surrounding communities. 
 
Eligible subjects will be asked to take a single dose of ivermectin (3-4 
tablets depending on weight) and undergo three blood draws over the 
course of two days. They will be asked to remain at the CTRU for four 
hours after taking the drug. Subjects will receive $100 for completing the 
study. 
 
The study will be conducted at the Clinical and Translational Research 
Unit on the UGA Health Sciences Campus.  The Principal Investigator is 
Dr. Adrian Wolstenholme. 
 
For more information, call: 706-713-2721 or email ctru@uga.edu  
 


Telephone Eligibility Screening Consent Script 
 
Study: Ivermectin and human immunity 
 
 
Thank you for calling the Clinical and Translational Research Unit to find out more about the research 
study entitled, Ivermectin and Human Immunity.  My name is _______________[study team member 
doing screening].   I am one of the researchers helping with this study at the University of Georgia.  
 
The purpose of this research study is to look at how a drug called ivermectin affects healthy people, in 
particular, whether it has an effect on the immune system. Ivermectin is used to treat infections with 
parasitic worms and we hope that this study will help us understand how the drug works. Do you think 
you might be interested in participating in this study?  
 
{If No}:  Thank you very much for your time. 
 
{If Yes}:  Before enrolling people in this study, we need to ask you some questions to determine if you 
are eligible for this study.  What I would now like to do is to ask you some questions about yourself.  This 
should only take about 5 minutes of your time. 
 
There is a possibility that some of these questions may make you uncomfortable or distressed; if so, 
please let me know.  You don’t have to answer those questions if you don’t want to.  
 
All information that I receive from you during this phone interview, including your name and any other 
information that can possibly identify you, will be strictly confidential and will be kept under lock and 
key.  Remember, your participation is voluntary; you can refuse to answer any questions, or stop this 
phone interview at any time without penalty or loss of benefits to which you are otherwise entitled. 
 
Do I have your permission to ask you these questions? 
 
{If No}:  Thank you very much for your time. 
 
{If Yes}:  Are you:  
1. Within the ages of 18-65 years old, inclusive; 
2. Healthy and have a weight over 110 lbs, and under 185 lbs; 
3. Willing and able to undergo multiple blood draws; 
4. A stable resident of the Athens area? 
{If No to any questions}:  Unfortunately you are not eligible for this study. All the information you gave 
me will be immediately destroyed. Thank you very much for your time. 
[If yes to all, proceed to next questions] 
(Exclusion Criteria): 
1. Are you pregnant or breastfeeding; 
2. Have you ever been told that you are immunosuppressed or have a problem with your immune 
system; 


4. Have you travelled to West or Central Africa in the past three years, or any other country where river 
blindness is present? (If asked, the specific countries of concern are Angola, Benin, Burkina Faso, 
Burundi, Cameroon, Central African Republic, Chad, Republic of Congo, Côte d’Ivoire, Democratic 
Republic of the Congo, Equatorial Guinea, Ethiopia, Gabon, Ghana, Guinea, Guinea-Bissau, Kenya, 
Liberia, Malawi, Mali, Mozambique, Niger, Nigeria, Rwanda, Senegal, Sierra Leone, South Sudan, Sudan, 
Togo, Uganda, United Republic of Tanzania, Yemen, plus a very isolated region on the Brazil/Venezuela 
border. The rest of Brazil is safe.) 
5. Do you have any known allergies? (Those that would cause ineligibility are: ivermectin/Stromectol, 
cellulose, pregelatinized starch, magnesium stearate, butylated hydroxyanisole, citric acid or 
cornstarch).   
 
6. Do you have hepatitis? 
 
7. Are you currently taking warfarin? 
 
{If Yes to any of these questions}:  Unfortunately you are not eligible for this study. All the information 
you gave me will be immediately destroyed. Thank you very much for your time. 
[If No to all of these questions]: You are eligible to participate in the study and I would like to extend 
you an invitation to participate in this research. If you decide to participate in the study, there will be 
two study visits on consecutive days. Before the first visit we ask that you not eat anything solid for two 
hours before visiting CTRU, as the tablets we are using work better on an empty stomach. Normal drinks 
such as water, coffee and juice are fine. The first visit will last about 5 hours, and we will provide a light 
meal during this time. Is that acceptable? 
[If No to this question]: Unfortunately you are not eligible for this study. All the information you gave 
me will be immediately destroyed. Thank you very much for your time. 
[If Yes to this question]: Thank you. The second visit will last less than 1 hour and will be 24 hrs after the 
start of the first visit. Compensation of $100 is available for completing the study. The first study visit 
will involve going through the consent process, being weighed and providing a blood sample. We will 
not take any permanent record of your weight, this is only so that can give you the correct number of 
tablets. You will then be given some tablets; these tablets may be ivermectin, the drug we are studying, 
or a placebo. The number of tablets you will be given depends on your weight.  We will ask you to wait 
with us for four hours, at which time another blood sample will be taken. On the second visit, we will 
take a third blood sample. To participate, we ask that you come to the Clinical and Translational 
Research Unit located on the Health Sciences Campus of the University of Georgia. At the first visit, the 
purpose of the research along with all of the procedures that you will be asked to complete as part of 
the research study will be explained in detail. We will give you an opportunity to have all of your 
questions about the research answered before you decide to enroll in the study. You can refuse to 
participate or stop taking part in the study at any time without giving any reason, and without penalty or 
loss of benefits to which you are otherwise entitled.  
 
Are you still interested in participating in the study? 
 


{If No}:  Thank you very much for your time. 
 
{If Yes}: We can schedule a convenient time for you to come to the CTRU. 
 
[Schedule time to come to CTRU. Record name, phone number and email address for reminder 
notifications.]  


Fasting Instructions for Participants 
 
This study uses a drug named Stromectol, which is absorbed better into the body if it is taken on 
an empty stomach. For this reason, we request that you do not eat anything solid for two hours 
prior to your first visit to the CTRU. Drinks such as water, coffee and juice are fine, but not 
energy drinks or smoothies. We will provide a light meal during this first visit after you have 
taken the tablets. 
 
Thank you for volunteering for the study and for your cooperation with this request. 


UNIVERSITY OF GEORGIA 
CONSENT FORM 
Ivermectin and Human Immunity 
 
Researcher’s Statement 
We are asking you to take part in a research study.  Before you decide to participate in this study, 
it is important that you understand why the research is being done and what it will involve.  This 
form is designed to give you the information about the study so you can decide whether to be in 
the study or not.  Please take the time to read the following information carefully.  Please ask the 
researcher if there is anything that is not clear or if you need more information.  When all your 
questions have been answered, you can decide if you want to be in the study or not.  This process 
is called “informed consent.”  A copy of this form will be given to you. 
 
Principal Investigator: 
Dr. Adrian Wolstenholme 
 
 
 
 
Department of Infectious Diseases 
 
 
 
 
706-542-2404  
adrianw@uga.edu 
 
Purpose of the Study 
Ivermectin is an FDA-approved drug used for the treatment of infections with parasitic 
nematodes (roundworms) in people. Every year it is given to hundreds of millions of people 
worldwide as part of international efforts to eliminate serious tropical diseases, river blindness 
and lymphatic filariasis (elephantiasis). Despite this, we really do not understand how the drug 
works against the parasites that cause these diseases, so the purpose of this study is to test the 
idea that the drug works together with the human immune system to remove the parasites.  
 
Study Procedures 
If you agree to participate, you will be asked to visit the Clinical and Translational Research Unit 
(CTRU) Building twice on consecutive days. You will be asked to remain at the CRRU for 5 hours 
on the first day to complete the procedures which will include providing information about your 
race, ethnicity, age and gender. In addition, additional screening criteria will identify anyone who 
may not be eligible for the study. You will review and sign a copy of this consent form with CTRU 
staff to give your permission to enter the study. A trained research nurse will draw 18ml (a little 
more than one tablespoon) of blood from you using standard phlebotomy techniques, and you 
will be weighed. We will not keep any permanent record of your weight, this is only so that give 
you the correct number of tablets. You will then be given three to four tablets (depending on 
your weight) to take. These will either be ivermectin (marketed as Stromectol in the USA), or a 
placebo. Which kind of tablet you will get will be determined completely by chance. You will not 
know which you have been given. You will be asked to wait in the CTRU for an additional four 
hours, after which a second sample of blood (15ml) will be taken. You will then be free to leave. 
We will provide a light meal after you have taken the tablets, which are best taken on an empty 
stomach. On the second day, the visit should last less than 1 hour. A third blood sample (18ml) 
will be drawn, approximately 24 hours after you took the tablets. We will then analyze the blood 
samples to determine if the drugs increase the ability of the blood cells to kill the parasites. 


Risks and Discomforts 
The risks and discomforts associated with your participation are related to the blood draws and 
possible side effects of the ivermectin. Ivermectin is generally considered to be very safe, but has 
not been extensively tested in pregnant women or immunosuppressed people. In clinical trials, 
the following clinical adverse reactions were reported as possibly, probably, or definitely related 
to the drug in 1-4% of the patients: nausea, diarrhea, changes in white blood cell count, 
abnormalities in liver function, swelling of the face, swelling of the arms/legs, blood pressure 
drop when standing up quickly, fast heart rate and muscle pain. Drug-related headache occurred 
in <1% of patients (0.2%).  If you are infected with a parasitic worm called Loa loa (the eyeworm) 
or Onchocerca volvulus (the parasite that causes river blindness), ivermectin may cause a severe 
reaction to dying worms. In order to avoid this, please do not take part in the study if you have 
travelled in the past 3 years to West or Central Africa (as this is the region of the world where it 
is possible to become infected with Loa loa) or other countries in which Onchocerciasis may be 
contracted. In addition, if you are currently taking Warfarin or have hepatitis you are not eligible 
to take part in the study. You will be required to stay at the CTRU for four hours after taking the 
dose of ivermectin in order for nursing staff to monitor you for any possible adverse effects, and 
will give prompt medical attention in case of any adverse effects. Risks associated with drawing 
blood include redness, swelling, pain or discomfort, and bruising at the site of the needle stick. 
Although rare, infection may also occur. Some people may experience dizziness, lightheadedness, 
and/or fainting. The CTRU nurses are very experienced in blood draws and will try to minimize 
any discomfort or bruising. 
 
Benefits 
This study will not directly benefit you. However, it will benefit society. A better understanding 
of individual people’s response to the parasite may help in the ongoing effort towards global 
elimination of river blindness and lymphatic filariasis. 
 
Incentives for participation 
If you choose to volunteer, we will ask you to sign this consent form.  We will provide you with 
$100 as compensation for completing the study, however, if you do not complete the study, you 
will be compensated $25 for each blood draw that you do complete, plus $25 for taking the 
ivermectin or placebo. This will be paid in cash after your second and final visit to the CTRU. You 
will be asked to sign a form verifying that you received this compensation. 
 
Privacy/Confidentiality  
To ensure confidentiality, you will be assigned a code and your samples will be assigned a random 
number and we will not attach any personal tracking information to any of the samples collected 
from you. We do ask you to consider providing the following information for us on a separate 
questionnaire form: race, ethnicity, age, and gender. This information will be linked to your blood 
sample, to experimental results obtained using the blood sample and will be reported to the 
National Institutes of Health, the main funder of medical research in the United States. Providing 
this information is entirely optional. If you decide to provide this information, please complete 
the questionnaire before the first blood donation. Researchers will not release identifiable results 
of the study to anyone other than individuals working on the project without your written 


consent unless required by law. The project’s research records may be reviewed by Food and 
Drug Administration and by departments at the University of Georgia responsible for regulatory 
and research oversight. 
 
A description of this clinical trial will be available on http://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. ClinicalTrials.gov is a website that provides information 
about federally and privately supported clinical trials. You can search this Web site at any time. 
 
Taking part is voluntary 
Your involvement in the study is voluntary, and you may choose not to participate or to stop at 
any time without penalty or loss of benefits to which you are otherwise entitled. If you decide to 
withdraw from the study, the information that can be identified as yours will be kept as part of 
the study and may continue to be analyzed, unless you make a written request to remove, return, 
or destroy the information. 
 
If you are injured by this research 
The researchers will exercise all reasonable care to protect you from harm as a result of your 
participation. In the event that any research-related activities result in an injury, the sole 
responsibility of the researchers will be to arrange for your transportation to an appropriate 
health care facility. If you think that you have suffered a research-related injury, you should seek 
immediate medical attention and then contact Dr. Adrian Wolstenholme right away at 706-542-
2404. In the event that you suffer a research-related injury, your medical expenses will be your 
responsibility or that of your third-party payer, although you are not precluded from seeking to 
collect compensation for injury related to malpractice, fault, or blame on the part of those 
involved in the research. 
 
If you have questions 
The main researcher conducting this study is Dr. Adrian Wolstenholme, a Professor at the 
University of Georgia, who is assisted by Dr. Barbara Reaves, a Senior Research Scientist.  Please 
ask any questions you have now. If you have questions later, you may contact Dr Wolstenholme 
at adrianw@uga.edu or at 706-542-2404.  If you have any questions or concerns regarding your 
rights as a research participant in this study, you may contact the Institutional Review Board (IRB) 
Chairperson at 706.542.3199 or irb@uga.edu. 
 
Research Subject’s Consent to Participate in Research: 
To voluntarily agree to take part in this study, you must sign on the line below.  Your signature 
below indicates that you have read or had read to you this entire consent form, and have had all 
of your questions answered. 
 
 
_________________________    
 
_______________________  
_________ 
Name of Researcher  
 
 
Signature 
 
 
 
Date 
 


 
_________________________    
 
_______________________  
__________ 
Name of Participant  
 
 
Signature 
 
 
 
Date 
 
Please sign both copies, keep one and return one to the researcher. 


Statistical Analysis Plan 
 
Changes in Cytokine Levels 
Cytokine levels were obtained from the Luminex data. The mean level plus or minus standard error of 
each analyte were calculated for each arm at each time point (0, 4 , 24 hrs post-treatment). For the control 
and ivermectin arms, levels at 4 hrs and 24 hrs post-treatment were compared to the levels pre-treatment 
using simple t-tests to determine if any individual results required further investigation, taking p = <0.05 
as the level of significance. Since none of the individual analyte results met this criterion, no further 
analysis was carried out. 
 
Changes in Gene Expression  
The Nanostring data were analysed on their proprietary software, nSolver™ (Nanostring Technologies 
Inc, Seattle). The data passed quality control criteria. The software calculated the log2 geometric mean 
levels of each mRNA measured and used t tests to determine statistically significant changes in 
expression between 4 and 24 hrs post-treatment for the control and ivermectin arms. The Benjamini-
Yekutieli False Discovery Rate method was used to account for the expectation that significant changes in 
genes may be correlated with or dependent on each other, and the subsequent resulting FDR adjusted p-
value of <0.05 used to determine those changes that were deemed to be statistically significant. 
 
Complete Blood Counts 
The mean numbers of each cell type were calculated for each arm at 24 hrs post-treatment and compared 
to those pre-treatment using a simple t-test, with p = <0.05 as the level of significance. Since none of the 
measurements passed this test, no further analysis was performed.