Clinical trial NCT02542410
Conditions: Endometriosis
Sponsor: Boston Children's Hospital
Start date: 2016-05-01; Completion date: 2018-09-01
Enrollment: 10 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The proposed pilot study will estimate the efficacy and safety of a novel therapeutic agent, cabergoline, with a clinical standard therapy, norethindrone acetate, for the treatment of endometriosis-associated pain in young women with endometriosis.

Detailed description:

Arms: arm 1: Norethindrone acetate 5 mg po daily x 6 months arm 2: cabergoline 0.5 mg PO twice weekly x 6 months
Interventions: intervention 1: Cabergoline intervention 2: Norethindrone acetate
Intervention descriptions: intervention 1: None intervention 2: None

Protocol documents:
Prot_000.pdf: 
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Title: Novel Treatments for Endometriosis (NOTE): Dopamine Receptor Agonist Therapy for Pain Relief in
Women Suffering from Endometriosis Pilot Study
General Information
1
* Protocol Title: 
The NOTE Study: Novel Treatments for Endometriosis
Maximum of 230 characters may be entered.
2
Full Title - If protocol title exceeds the 230 characters limited from field above, enter full title here.
Otherwise, leave blank.
Novel Treatments for Endometriosis (NOTE): Dopamine Receptor Agonist Therapy for Pain Relief in
Women Suffering from Endometriosis Pilot Study
3
* Provide a brief summary (in lay terms) of the research protocol.
Endometriosis is a chronic illness which begins during adolescence and young adulthood. Current
therapies for endometriosis are suboptimal, leaving many women trying to cope with chronic pain. Novel
therapies are desperately needed to ameliorate the chronic course of this disease, and prevent ongoing
suffering for these women. In this pilot study, we aim to estimate the efficacy and safety of a regimen of
norethindrone acetate (a standard therapy) or cabergoline (a novel agent) for alleviating pain symptoms in
young women with endometriosis. The results of this pilot study will be used to inform a future, larger
randomized controlled trial.
4
* Principal Investigator (PI):   Amy DiVasta 
4.1 * To serve as a PI you must qualify under one of the following eligibility requirements.
(Residents, interns, fellows and postdoctoral candidates are not permitted to be PIs). Please
select the appropriate category that applies to you.
Physicians, Dentists and Psychologists credentialed through the hospital with the BCH medical staff
registrar as an active medical staff member and having an appointment of Instructor or higher at
Harvard Medical School.
 
If Other patient services professionals:
4.1.1 Research is part of your scope of employment responsibility and not to meet a training or
degree requirement. Please explain how this research falls within the scope of your
responsibilities at the hospital.
4.1.2 You have training and experience and confirmed clinical research competencies. Please
explain your training and experience in clinical research.
4.1.3 Are you employed at Children’s as a nurse or do you have nursing credentials through
Boston Children’s Hospital?
Please note if this is checked yes, in accordance with the policies of the Nursing
Department your protocol will be sent to the Nursing department for both scientific review
and departmental sign off.
  Yes No
5
* Type Of Submission:
New Research Activity
**New Research Activity Limited to Secondary* Use of Biological Material and Data

Establishment of Human Biological Specimen Repository/ Data Registry (only) – repositories/registries
are defined as a prospective collections of specimens or data that are processed, stored, distributed to
multiple investigators for use in research.
Request for Exemption
Individual Patient Expanded Access
Humanitarian Use Device (HUD)


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Reliance on Another IRB
Projects that lack immediate plans for involvement with human subjects, their data and/or their
specimens (i.e.training grants)
** Use this form only if: 
1) specimens/data are not identifiable or 
2) specimens/data are identifiable but recorded by PI in de-identified format or meet the waiver of HIPPA
authorization criteria listed below All other uses of secondary specimens/data must be submitted on a new
research activity form.
* Secondary means the tissue or data will be or was collected for a primary or initial purpose other than the
research ( i.e data from medical records, tissue from pathology)
Waiver of HIPPA authorization (all criteria must be met) 
• The proposed use of this data/document/record/specimen presents no more than   minimal risk to the
privacy of individuals 
•The research could not practicably be conducted without the waiver of HIPPA authorization 
• The research could not practicably be conducted without access to and use of protected health information
with identifiers 
• Waiving HIPPA authorization will not adversely affect the subject’s rights or welfare
This form may not be selected if the study involves interaction/intervention with subjects in order to obtain
tissue/data specifically for this research.
6
* Is this protocol related to child health (including perinatology, prenatal assessments, childhood
antecedents of adult disease, and long-term follow up of pediatric disorders)?
  Yes No
7
* Is this protocol related to cancer (primarily concerning malignancies, oncology patients, or involving
use of malignant tumors)?
  Yes No
Note: If YES, your protocol will require review by the Dana Farber IRB instead. 
For details, see: Catalyst and Dana Farber Cancer Center Reliance Agreements
8
* Will this protocol utilize any of the services of the ETU (Experimental Therapeutics Unit)? 
Please select "No" for the following types of submission:
     1. Request for Exemption
     2. Projects that lack immediate plans for involvement with human subjects, their data and/or their
specimens (i.e.training grants)
  Yes No
These services include:
Use of space on the ETU or research space at Waltham
Nursing assistance at above sites
Off-site nursing and/or research coordinator services provided through ETU
Specimen collection or processing, sample storage and preparation for shipping
Assistance from nutritional Metabolic Phenotyping Core (preparation of research meals, analysis of
food records, etc.)
Use of specialist equipment located on the ETU (3DMD camera, DXA, pQCT, V-max, etc.)
 
First Name
Last Name
CHID# (if applicable)
BCH Department (if applicable)
Email Address
Research Team
 
 
If the person you need to add to your protocol cannot be found using the “Add” buttons below, please send
an email to CHERP Support (cherp.support@childrens.harvard.edu) requesting that the person be added
to the Research Staff. CHeRP Support will need the following information:
 


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1
Research Staff - Children's Hospital Employees only:
 
Last
Name
First
Name Role
Editor CC on
Correspondence
Required
Training
Completed
CHeRP
Training
Date
Modified
Date
Created
View Gallagher Jenny Research
Coordinator/Assistant
yes
yes
yes
yes
6/3/2015
6/3/2015
View Hale
Andrea Other Research
Support
no
no
yes
yes
11/28/2017 11/28/2017
View Laufer
Marc
Co-Investigator
no
no
yes
yes
6/3/2015
6/3/2015
View Missmer
Stacey Co-Investigator
no
no
yes
yes
6/3/2015
6/3/2015
 
2
NOTE: Accounts are no longer required for non-BCH researchers. These individuals remain under
the jurisdiction of their home institution’s IRB and should not be listed here. If you think there is a
special circumstance, please contact your IRB Administrator. 
Research Staff - Non Children's Hospital Employees only:
 Last Name
First Name
Role
Email
Required Training Completed
There are no items to display
 
3
PI: Amy DiVasta  
Completed Training Courses:
Training Program
Continuing Education Description
Training
Completed
Date
Created
Continuing Education
EQuIP: IND/IDE Pre-review
10/25/2016
 
Continuing Education
Collaborative IRB Training Initiative (CITI
Continuing Education)
7/12/2016
7/12/2016
Continuing Education
Continuing Education/Department Meeting
3/10/2015
 
Collaborative IRB Training Initiative (CITI
Biomedical)
 
9/11/2012
9/11/2012
CHeRP Training
 
10/26/2010
 
CHeRP Training
 
10/26/2010
 
Continuing Education
Collaborative IRB Training Initiative (CITI
Continuing Education)
9/2/2009
11/8/2010
Continuing Education
Continuing Education/Department Meeting
8/16/2006
11/8/2010
Collaborative IRB Training Initiative (CITI
Biomedical)
 
2/4/2004
11/8/2010
Collaborative IRB Training Initiative (CITI
Non-Interventional)
 
2/4/2004
11/8/2010
 
4
Reliance PIs - Employees who are listed on existing Reliance on BCH protocols.
 
Last
Name
First
Name
Institution
Completed Training
View Hornstein
Mark
Brigham & Woman's Hospital
(BWH)
Training Received at Another Institution(1/29/2015
)
Continuing Education(7/27/2006 )
Training Received at Another Institution(7/6/2009 )
Training Received at Another Institution(9/30/2000
)
Training Received at Another Institution(9/30/2000
)
Training Received at Another Institution(4/9/2012 )
Reliance Agreement Training(1/29/2015 )
 


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5
Research Team Members - Employees who are listed on existing Reliance on BCH protocols:
 
Last
Name
First
Name
Employee
ID
Role
Reliance Institution
View Fraer
Cameron 601480
Research
Coordinator/Assistant
Brigham & Woman's Hospital (BWH) -
FWA00000484
View Hornstein Mark
600364
Co-Investigator
Brigham & Woman's Hospital (BWH) -
FWA00000484
View Laufer
Marc
602498
Co-Investigator
Brigham & Woman's Hospital (BWH) -
FWA00000484
View Missmer
Stacey
82999
Co-Investigator
Brigham & Woman's Hospital (BWH) -
FWA00000484
 
 
 
Title: Novel Treatments for Endometriosis (NOTE): Dopamine Receptor Agonist Therapy for Pain Relief in
Women Suffering from Endometriosis Pilot Study
Funding Sources
1
* Select funding category.
Externally sponsored (federal, state, corporate, foundations)
Internally sponsored
Externally and internally sponsored
No sponsor
Private Donor
1.1 If internally sponsored - select as appropriate: 

Department/ Division or Children’s foundation funds

Internal Children’s Grant Award
1.2 Enter any additional information if applicable: 
Supported with funds from the Marriott Family Foundation
1.3 If the protocol does not have a sponsor, please detail how the study will be conducted
without funding.
1.4 Please provide the name of the private donor.
 
Funding Sources - Details
1
* List of external sponsors for this protocol.
 
Sponsor
Funding Category
View J WILLARD AND ALICE S MARRIOTT FOUNDATIO - 1754
External Foundation
View MARRIOTT DAUGHTERS FOUNDATION - 1822
External Foundation
 
Financial Disclosure
1
* Do you or any person affiliated with the protocol have or expect to have any investment or
financial relationship (examples below) with any entity that is providing funds or other support in
connection with the protocol? 
  Yes No


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If YES:
1.1  Please select the relationships as appropriate.

Consulting

Payments for protocol/study design

Protocol-related payments not included in the research agreement budget

Stock or Options

Honoraria

Scientific Advisory Board Membership

Royalties or license fees related to the protocol, or to any test article or device which will be
employed in the conduct of the research under the protocol (including any royalties or
license fees received through an academic institution, including Children's Hospital).

Equipment or other laboratory support

Other support for research unrelated to the protocol

Support for educational or other academic or medical efforts

Other Grants

Other
2
* Do you or any person affiliated with the protocol have or expect to have any proprietary
interest related to the protocol, or related to any test article or device that will be employed in the
protocol?  Include proprietary interests that you have assigned to any entity, including any
institution you have been affiliated with. 
  Yes No
If YES:
2.1 Please select the proprietary interest as appropriate.

Patent-licensed, in whole or part, to an entity providing funds for the research

Patent-licensed, in whole or part, to another entity

Other
3
* Do you or any person affiliated with the protocol have or expect to have any advisory role,
appointment, or employment with any entity that is providing funds or other support for the
research to be conducted under the protocol?
  Yes No
If YES:
3.1 Please select as appropriate.

Scientific Advisory Board Membership

Other Advisory Role

Officer

Director

Employment

Other
4
* Do you or any person affiliated with the protocol have or expect to have any financial interest,
financial relationship, or position or advisory role with any other entity that may be affected by
the research to be conducted under the protocol (e.g. competitor, customer, collaborator or
commercial sponsor affiliate)?  Include any entity that may be benefited or harmed, directly or
indirectly.
  Yes No
5
* Do you or any person affiliated with the protocol  have or know of any arrangement or


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understanding, tentative or final, relating to any future financial interest, financial relationship,
future grant, position, or advisory role either related to the protocol, or dependent on the
outcome of the research under the protocol?      
  Yes No
6
* The IRB prohibits special incentives in connection with clinical research, including, finder’s
fees, referral fees, recruitment bonuses, enrollment bonuses for reaching an accrual goal, or
similar types of payments. Will you or anyone else in connection with the conduct of any
research under the protocol receive money, gifts or anything of monetary value that is above and
beyond the actual costs of enrollment, research conduct, and reporting of results, from the
sponsor or any other entity? 
  Yes No
7
* Is there anything not disclosed above which you believe might constitute a conflict of interest
or an appearance of a conflict of interest in connection with the protocol?   
  Yes No
8
If any of the questions above are checked "Yes", please provide the name of the individual for
whom the disclosure is made and describe in further details the disclosure. This section must
include a full description of the financial relationship, including but not limited to, a detailed
description, as applicable, of any test article of device involved; the advisory role or
appointment; the competitor, customer, collaborator; any arrangement related to the research;
and so on. Please also include actual amounts of any consulting  or other monies received and
the time period for which it was received. This section will not be reviewed without a full
disclosure.
9
Upload any other pertinent documentation.
Name
Date Last Modified
Version
Owner
There are no items to display
 
Protocol Design
1
* Is this a multi center study?
  Yes No
If YES:
1.1  Is Children’s Hospital, Boston the lead site or coordinating center?
  Yes No
 If YES:
1.2 Describe the plan to ensure communication among sites in terms of adverse events,
unanticipated problems, protocol modifications, interim results, etc.
While CHB is the coordinating center, this is truly a joint venture between CHB and BWH. Study
staff will be employed at both institutions. Weekly Boston Center for Endometriosis meetings are
held on an ongoing basis, so that study staff will be in constant contact regarding study progress
and any adverse events and deviations from protocol. 
A reliance agreement has proposed, and already completed, and we are asking BWH to cede
review to CHB.
2
*  Is the person who will be primarily responsible for conducting the study at BCH different from the
PI? 
  Yes No
3
* Has the PI, or if question #2 was YES has that person, previously served as a PI of a protocol
involving interaction/intervention with human subjects at CHB?   
  Yes No
 
Subject Information


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1
Enrollment Numbers
1.1 * Specify the number of subjects enrolled at Boston Children’s Hospital, or at sites relying
on BCH IRB review, that are required to complete data analysis.
10 subjects
1.2 If a larger number of subjects must be enrolled to account for such things as screening
failures and drop-outs, please indicate the total number of subjects to be recruited at BCH
or at relying sites. If not applicable, please leave blank. 
14 subjects
1.3 If this is a multi-center study, please specify the total number of subjects required to
enrolled across all sites, including BCH and reliance sites, for data analysis.
10 subjects
1.4 If this is a multi-center study and a larger number of subjects must be enrolled across all
sites to account for such things as screening failures, drop-outs, and lost to follow-up,
please indicate the total number of subjects to be enrolled.  
If not applicable, please leave blank.
14 subjects
2
Types of Subjects
2.1 *Gender
Males
Females
2.2 *Age
Neonates (up to 30 days)
Infants (between 30 days and 2 years)
Children (between 2-12 years)
Adolescents (between 13-17 years)
Adults, Ages 18-35
Adults over 35 
Specify entire age range.
15-40 years
2.3  Special Populations
Mentally Incapacitated
Employees/Staff (Note: Employees/staff under the direct supervision of the PI may not be recruited.)
Normal/Healthy Controls
Students
Specify from where.
Pregnant Women/Fetuses
Prisoners/Incarcerated Youth (this would include children under the care of the Department of Youth
Services). Consider if your target population will be or at higher risk of incarceration. If this category is
chosen, you will be prompted to answer additional questions to meet federal regulations.  
Wards of the State (consider if your target population may contain wards of the state or children at risk
of becoming a ward of the state (this includes foster children or any child that is in state custody))
Minorities 
If NOT checked:
Provide scientific justification for excluding minorities.
Non-English Speaking Subjects
If checked:
What plans do you have to provide the subject/family with a written translation of the consent
form and other study materials and to ensure that all study interaction will be in a language


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understandable to the subject/family? 
If NOT checked:
Please provide scientific justification for excluding non-English speaking subjects.
In addition to the fact that there is no known difference in endometriosis prevalence with regards to
race and ethnicity, the additional burden of translation services on personnel and funding would make
performing the study impossible. As noted above, the consent process will be in-person and there will
be three in-person CTSU visits, all of which would require translator services. In addition to the
consent form, there are multiple questionnaires that would all need to be translated into multiple
languages. The requirement to include non-English speaking individuals would be unusually
burdensome for a study of this magnitude.
Other populations potentially subject to special considerations not identified above (i.e. socially,
educationally, economically disadvantaged, elderly, terminally ill or adults with questionable decision
making capabilities)
Specify population.
Specify what additional safeguards will be taken to protect the rights and welfare of these
subjects.
Adults With Decisional Impairment
*Decisional Impairment is defined as: persons who have impaired ability to make decisions as a result
of intellectual or mental health challenges as well as individuals who have lost capacity to
make decisions because of clinical situations such as unconsciousness.
Please describe the type and range of decisional impairment of the adult subjects to be
included in the research.
Provide a rationale for why it is necessary to include adults with decisional impairment as
participants in research, including information regarding the potential benefit to the
individuals in relationship to potential risks.
Describe the criteria and procedures or measurements for evaluating the  decisional status of
the prospective participant to determine whether they are capable of consenting on their own
behalf. This would include the use of standardized measurements, consults with another
qualified professional, etc...
Describe how persons authorized to obtain legally valid consent will be identified in the event
any individual is judged incapable of consenting on their own behalf. Please review the IRB
policy to the right of this question that describes the requirements for determining a legally
authorized representative for the subject.  Briefly, these are court-appointed guardians, health
care proxies, or durable power of attorney.  Please note that family members are not
automatically considered for this role and may only be permitted when there is documentation
that neither of the previous exist.Please also explain how legal records regarding authority will
be obtained, reviewed by the research team, and documented in the research record.
When possible if legally valid consent cannot be obtained from the subject, assent should be
obtained. Please describe if you plan to obtain assent and provide criteria used to evaluate the
assent or dissent of the adult with decisional impairment.
If applicable to your population, provide a description of how the participant will be protected
if their capacity to consent is lost or fluctuates.  What provisions have been made to protect
the subjects's rights?  This may include the use of an ombudsman, frequent cognitive status
evaluations, etc...
 
Study Location
1.  If your research is conducted in any  of the following location(s) please check  all that
apply. If your research does not include any of these sites, please leave the questions blank.

Adolescent Medicine

Adolescent Surgery

Cardiac ICU

Cardiac Surgery


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
Infant Toddler Surgical

Infant/Toddler Medical

Intermediate Care Program (ICP, 11 South)

Medical/Surgical ICU (7 South)

Medicine ICU (11 South)

Neonatal ICU

Neurology

Oncology/Hematology

Psychiatry

School Age Medical

School Age Surgical

Sleep Study

Solid Organ Transplant

Stem Cell Transplant
Other CH Locations

Cardiac Cath Lab

Children’s Hospital Primary Care Center (CHPCC)

Clinical and Translational Study Unit (CTSU)

Emergency Department

Martha Elliot Health Center (MEHC)

MRI

Nuclear Medicine/PET

OR/PreOp/PACU

Other Satellites (Lexington, Peabody, South Shore, etc.)

Radiology
Off Premises e.g. Schools, other Hospitals, Home

Beth Israel Deaconess

Brigham and Women’s Hospital

Boston Medical Center

Dana Farber Cancer Institute

Harvard Medical School

Harvard School of Public Health

Subject's Homes

Joslin Diabetes Center

Mass Eye and Ear Infirmary

Mass General Hospital

MIT

Other

Physician Office

School


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
Tufts – New England Medical Center
1.1 If Other:
Specify:
221 Longwood Ave, Boston, MA 02115
 
Recruitment and Remuneration
Recruitment
1
* Describe plans for recruitment, including identification of potential participants, who is responsible
for recruitment and how and when subjects will be recruited.
Potentially eligible participants will be identified during visits to the Pediatric Gynecology program at BCH
(including satellite sites) or the CIRS or MIGS programs at BWH. Patients will be identified by their clinical
provider as potentially eligible. 
If the patient is interested, the provider will contact the study team. An IRB-approved study brochure may be
given to the patient, to allow her to contact the study team directly. A study coordinator or another member of
the study team will meet with the patient to discuss options for involvement.
In some instances, providers may wish to give blanket approval for the study team to contact their patients,
rather than referring individual patients. In these instances, the study team will contact patients through the
mail or email with a recruitment letter (appendix L), and then follow up with the patient (by phone or email, if
patient approved for research) one week later. This allows patients of very busy providers the opportunity to
participate in the study. Patients are able to opt out of the follow up call/email by returning the opt out postcard
(Appendix N) to the study team. Providers who give patient contact information to study staff will be only IRB-
approved participants in the research. 
We will also recruit by posting IRB-approved brochures in the waiting rooms of the clinics and other hospital
areas and in local clinics. After a patient expresses interest in participating in the trial, a research assistant or
another approved member of the study team will meet with the patient/family to discuss options for
involvement and to sign the consent form. Prior to enrollment, patients will be asked what their highest
endometriosis pain score has been within the last month. Only those patients with a score of 3/10 or greater
will be eligible to enroll.
In addition, potentially eligible participants from the Boston Center for Endometriosis (BCE)’ "Women’s Health
Study: from Adolescence to Adulthood" cohort (CHB IRB# IRB-P00004267) will be identified from the
enrollment logs of the BCE. Patients meeting inclusion criteria will be identified by the study team (all of whom
will jointly have IRB approved roles in the BCE Study and current proposed trial), and will be contacted by
their previously selected preferred method of contact (either phone, email, text) in the manner outlined below.
Patients may also be recruited from Craig's List, Facebook, and the BCH and Partners' research websites and
employee intranet pages, and will all be screened for eligibility by the study team. Recruitment materials may
also be made available at the Gynecology department's annual endometriosis patient day. 
2
* Will you need to search through BCH medical records or institutional databases such as i2b2 or
BCH360 for the initial screening for potentially eligible subjects?
  Yes No
If YES:
2.1 Will you be accessing records or contact information of patients not seen by your department,
your service or your co-investigators?
  Yes No
In general, recruitment of patients from services outside of the investigators’ area is not to be done
without involvement of the departments in which the patients were seen. 
If YES:
2.1.1 Please describe how you will coordinate with other departments or care providers during
the recruitment process.
3
If applicable, how will prospective subjects' healthcare providers (e.g., physician, dentist, etc.) be
involved in the recruitment and/or be notified of their individual patients' participation in the study? 
Subjects' healthcare providers may choose to give potentially eligible patients a study brochure, or refer
them to a study team member for further discussion regarding study participation. Participation or non-
participation in the study will not alter clinical care for patients in any way. 
Prospective subjects' gynecologic and primary care healthcare providers will be notified of their individual
patients' participation in the study by means of an email as well as a written letter, if agreed to by the
participant.


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4
* Describe measures that will be implemented to avoid participant coercion or undue influence.
All prospective participants will meet with a member of the study team trained in proper recruitment and
consenting of study participants. All prospective participants will be made aware that study involvement is
completely voluntary. Choosing to participate or not participate will not affect patients' care. The consent forms
will explicitly state that participation is voluntary and the decision to participate or not participate will not affect
a patient's clinical care.
5
* Does the recruitment strategy involve contacting individuals multiple times in an effort to secure
their enrollment into the study? 
  Yes No
If YES:
5.1 Please describe how frequently and in what manner individuals will be contacted.
Potentially eligible participants from the BCE "Women’s Health Study: from Adolescence to
Adulthood" Study cohort will be identified from the enrollment logs of the BCE. Patients meeting
inclusion criteria will be identified by the study team (all of whom will jointly have IRB approved
roles in the BCE Study and the crurent proposed trial). Patients will be first contacted using the
preferred method of contact (email, phone, text message) as indicated by the participant during
enrollment in the BCE study. If no preference is indicated, the default method of contact will be
email. If at any time a phone number, email, or mailing address is determined to be incorrect or
invalid, the research assistant will use an alternative method to contact the participant. If a phone
call is the participants preferred method of contact and they do not answer the phone call a pre-
scripted voicemail will be left. If participants do not respond to the first contact within two weeks, a
second attempt will be made. If no response occurs within two more weeks, a third attempt will be
made A total of 3 contacts – including voicemail, email, or text message will be made. If a subject
is not reached after 3 contacts, no further attempts to contact will be made. If a patient is
interested, a study coordinator or another member of the study team will meet with the patient to
discuss options for involvement. 
6
Upload all recruitment materials, including letters, brochures, posters, phone interview scripts,
newspaper ads, etc.
Name
Date Last Modified
Version
Owner
 Appendix H.Voicemail script for recruiting
11/17/2015 4:23 PM
0.02
Amy DiVasta
 Appendix I.Phone Enrollment Script
1/24/2017 4:04 PM
0.03
Amy DiVasta
 Appendix J.NOTE Email Enrollment Script
11/17/2015 4:23 PM
0.02
Amy DiVasta
 Appendix K.recruitmentflyer
12/20/2016 12:52 PM
0.06
Amy DiVasta
 Appendix L.recruitmentletter
11/17/2015 4:24 PM
0.02
Amy DiVasta
 Appendix M.recruitmentsmallcard
1/24/2017 4:06 PM
0.03
Amy DiVasta
 Appendix N.optout card
11/17/2015 4:24 PM
0.02
Amy DiVasta
 Appendix P.Text message script for recruiting
11/17/2015 4:24 PM
0.03
Amy DiVasta
 Appendix Q: Craig's List ad
12/20/2016 12:54 PM
0.05
Jenny Gallagher
 Appendix R: WHS facebook post
12/20/2016 12:55 PM
0.04
Jenny Gallagher
 Appendix S: BCE website post
12/20/2016 12:56 PM
0.04
Jenny Gallagher
 Appendix T: Trifold recruitment brochure
6/1/2017 3:15 PM
0.02
Jenny Gallagher
7
Please describe how each document uploaded in question #6 will be used.
Appendices K, M and T are printed recruitment materials used to advertise the study to patients. Appendix
L: provider recruitment letter and Appendix N: opt-out recruitment postcard will be sent to patients whose
providers approved contact outside of a clinic visit. 
Appendix Q will be posted in the Community Volunteers section of Craig's List Boston not more than once per
week, as well as on the BCH and Partners intranets and research pages. Appendix R will be posted on the
Women's Health Study: From Adolescence to Adulthood facebook page as well as the Center for Young
Women's Health website/social media with approved study images. The post directs interested patients to an
external website rather than soliciting any interaction on the facebook page. Appendix S will be posted on the
Research section of the Boston Center for Endometriosis website and may also be included on the Center for
Young Women's Health site.
Remuneration
8
* Will subjects/families receive a form of payment, compensation or reimbursement?
  Yes No
Please answer the following information regading ClinicalTrials.gov registration.


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9
* Into which of the following category(s) does this protocol fall (check all that apply):

(a) A controlled clinical investigation other than phase 1 of a drug subject to FDA regulation
(requires registration). CONTROLLED is defined as a design to permit comparison of a test
intervention with a control to provide a quantitative assessment of the drug/ effect. This can
include concurrent control groups as well as non concurrent controls including historical
controls or subjects as their own controls (requires registration by FDA regulations)

(b) Protocol prospectively compares a device-based intervention subject to FDA regulation against a
control in human subjects (requires registration). An INTERVENTION broadly includes various
techniques using the device such as, among other things device regimens and procedures, and use of
prophylactic, diagnostic or therapeutic agents. This applies to studies other than a small clinical trial to
determine feasibility of a device, or a clinical trial to test prototypes devices where the primary outcome
measure relates to feasibility and not health outcome. (Requires registration by FDA regulations)

(c) A device trial that is a pediatric post-market surveillance trial (requires registration by FDA
regulation)

(d) Protocol prospectively assigns human participants or groups of humans to one or more health-
related interventions to evaluate the effects on health outcomes.” Health-related interventions include
any intervention used to modify a biomedical or health-related outcome (for example, drugs, surgical
procedures, devices, behavioral treatments, dietary interventions, and process-of-care changes). Health
outcomes include any biomedical or health-related measures obtained in patients or participants,
including pharmacokinetic measures and adverse events. (ICMJE requires registration)

(e) Protocol does not meet any of the criteria above (a-d) but research will be registered on
clinicaltrials.gov (voluntary registration, statement optional)

(f) Protocol does not meet any of the criteria above (a-d) and research will not be registered on
clinicaltrials.gov
If (a), (b), (c), or (d) is checked, either FDA regulations or International Committee of Medical journal
Editors (ICMJE) Guidelines http://www.icmje.org/recommendations/browse/publishing-and-editorial-
issues/clinical-trial-registration.html require that this trial be registered on a clinical trial registry.  FDA
requires registration on ClinicalTrials.gov site. ICMJE requires registration on one of a broader list of
registries, including clinicaltrials.gov.  
For further information about required registrations you may go to: 
• http://clinicaltrials.gov/ct2/manage-recs ( FDA regulations)  
• http://www.icmje.org/recommendations/browse/publishing-and-editorial-issues/clinical-trial-
registration.html (ICMJE) 
Note if (a), (b) or (c) is checked, FDA regulations require that the consent form contains the following
statement:
"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 results. You can search this web site at anytime."
If (d) or (e) is checked you may voluntarily choose to include the statement above.  Please make the
appropriate updates to the consent form accordingly.
9.1 Who will be responsible for registering the trial?

Sponsor (if other than BCH PI/Sponsor-Investigator)

BCH PI or Sponsor-Investigator

Investigator at another site

Other
If Other:
9.1.1 Please specify who.
 
9.2 If you have selected CHB PI or Sponsor-Investigator do you have a Clinical Trial registration NCT
number for this study at this time?
  Yes No
If YES:
9.2.1 Please insert "NCT" number for this trial 
ClinicalTrials.gov Identifier: NCT02542410
NOTE:  A valid NCT number must be included before the IRB releases final approval for this protocol. If
the NCT number is not included in the original submission you will need  to register the trial and submit
an amendment to include  the NCT registration number before  final approval is released.


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Final approval for the protocol  will not be issued until a valid NCT number is listed in the CHeRP
smart form
 
Remuneration Details
Enter information about all forms of payment that will be used in this study and answer the corresponding questions. 
Please note, any payment or gift should not be so large as to unduly influence the parent/child to participate.
1.  Reimbursement: payment for research-related expenses incurred. E.g. transportation, parking, meals, childcare.
1.1 What form (check, cash) and total amount will be provided?
A parking voucher for hospital parking garage or MBTA single-ride Charlie card
1.2 Who will receive the reimbursement (subject, parent or both)?
Subject
1.3 When and how will the reimbursement be distributed?
For participants making a research-specific visit to CHB or BWH, a parking voucher or MBTA
single-ride Charlie cards will be provided at the time of the appointment to the participant.
1.4 How was this form and amount determined?
This was determined based on past studies at CHB.
2
 Compensation: payment for time and inconvenience from participation. E.g. compensation for time-off work.
2.1 What form (check, cash) and total amount will be provided?
2.2 Who will receive the compensation (subject, parent or both)?
2.3 When and how will the compensation be distributed?
2.4 How was this form and amount determined?
3
 Tokens of Appreciation: small payments or gifts for participation. E.g. toys, gift certificates, small payment.
3.1 What form (gift, payment) and total amount will be provided?
$225 in Amazon or Target gift cards
3.2 Who will receive the token of appreciation (subject, parent or both)?
Study subject
3.3 When and how will the token of appreciation be distributed?
Subjects will receive the tokens of appreciation upon the completion of the study, or upon
termination of study participation.
Subjects will be given one $75 gift card for each study visit completed.
3.4 How was this form and amount determined?
Amount were based on previous studies involving subjects recruited from the Adolescent Clinic
at CHB or from the CIRS Clinic at BWH. These gift cards will show subjects our appreciation for
the time taken to complete the questionnaires, provide blood samples, attend study visits, and
adhere to a daily medication regimen.
4
 Incentives: payments/gifts to encourage subject enrollment or continued participation. E.g. completion bonus.
4.1 What form of incentive and total amount will be provided?
4.2 Who will receive the incentive (subject, parent or both)?
4.3 When and how will the incentive be distributed?
4.4 How was this form and amount determined?
 
Research Data, Documents, Subject Reports & Consent/Assent Forms: Storage
1
*Where will research data, documents and subject reports be sent and stored? Check all that apply.
 Children's Hospital Medical Record
 Departmental Medical Record
 Separate Research Record


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
 Subject/family will receive results
 Sponsor, Collaborator and/or Coordinating Center 
Specify:
BWH
 Medical Record at another institution, hospital, physician’s office, etc. 
Specify:
 Research Registry 
Will data include patient identifiers (name, medical record, SS #)?
  Yes No
Other 
Specify:
2
*Where will the signed informed consent and assent be stored? Check all that apply.
 Children's Hospital Medical Record
 Departmental Medical Record
 Separate Research Record
 Sponsor, Collaborator and/or Coordinating Center
 Medical Record at another institution, hospital, physician’s office, etc.
 Research Registry
 Not Applicable
3
* Explain the rationale for including or not including research data and the informed consent/assent
forms in the CHB medical records.
Given that this is an interventional trial, knowledge of the medications that a subject may be randomized to
may be helpful to members of the subjects' healthcare team. As such, the consent form will be available to be
viewed in the medical record. 
For subjects who are not patients at BCH, operative reports will be collected to ensure they meet inclusion
criteria. These reports will be scanned into the newly created BCH medical record as source documentation.
Please note: the confidentiality section of the consent form must specify whether research data and/or the
informed consent/assent form(s) will or will not be included in the Children’s Hospital or Departmental medical
records.  A sample statement is included on the Informed Consent Template. 
 
Medical Expenses for Research Related Adverse Events
1
*How will the cost of reasonably foreseeable medical care in the event of a research related adverse
event be covered?
Corporate sponsor agreement
Likely to be covered by insurance
Philanthropic or other grant
Foundation or Departmental Funds
Interdepartmental arrangements
Other 
Explain:
Not applicable
 


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Privacy and Confidentiality
Privacy
1
* ‘Privacy’ refers to a person’s desire to control access of others to themselves. Describe the steps that will be taken to
protect and assure the privacy of the subject. 
Detail specific actions the Research Team will take to ensure that privacy is protected through each phase of the study
(e.g. access to medical records for recruitment, mailings to subjects, phone calls with subjects, research visits).
Patients with endometriosis will be approached about the study in the gynecology clinic where they receive clinical care. In most
cases, the treating physician will discuss participation in the study with the patient in a private office or treatment room, and will ask
if they are willing to speak with the study coordinator. The physician will provide each patient with a study brochure for her review.
Interested patients will meet with the study coordinator in a private setting to discuss involvement in the study. Patients will be
made aware the study is voluntary and participation will not affect clinical care. For all participants, the consent process will take
place in a private setting. Participants will be encouraged to ask questions and to illustrate full understanding of the study
procedure and risks/benefits. 
Other potential subjects may approach the study team in response to flyers posted in clinic, or given to them by their medical
provider at the time of a clinic visit. Phone calls with potential subjects to screen for eligibility for participation will also be conducted
in a private setting.
During research visits, participants will complete study questionnaires in a private room setting. 
Participants will determine their preferred means of communication (phone call, email, text), and if there are any means of
communication that they never wish to employ. When phone calls are made, the study will be referred to in general terms that will
not disclose the exact nature of study participation. Information which may identify the purpose of the study or the disease status of
the participant will not be recorded on voicemail or answering machine. 
Examples of issues:
• Potential subjects may not want to be approached for research purposes by someone they do not know. 
• Potential subjects may not want others to know they have a disease or were previously treated for a condition;
  therefore, you may want to avoid sending a recruitment letter in the mail that may be opened by others. 
• Subjects may not want to be seen in areas that may stigmatize them (i.e. pregnancy counseling center).
Confidentiality
2
* Investigators are required to obtain only the minimum data necessary to achieve the research goals. 
Please justify why the data you are obtaining is the minimum necessary.
For subjects, the date of diagnostic surgery, stage of endometriosis at diagnosis, and other comorbid health conditions will be
obtained from the medical record or by self-report from the patient. All participants will complete questionnaires regarding their
overall health, pain status, functional status, medical history, gynecological history, and mental health. These data are all necessary
to assure the patient's eligibility for participation, to quantify our outcome measures, and to account for confounding or mediating
factors that may impact the effects of our interventions. Identifying information from all data sources will be removed at collection.
All data samples will be identified by a randomly generated study ID number unique to each participant.
3
* Describe where data will be kept, how it will be secured and who will have access to the data.  If links to identifiers are
used, please describe the coding mechanism, whether the code is derived from subject information, and how and where
the mechanisms for re-identification will be protected and maintained.
Each participant will be assigned a unique study ID number which will be used to label and track all of her study data. Study ID
numbers will be randomly generated at the time of study enrollment. The date of collection will also be placed on each sample and
survey. To protect confidentiality, no names will be used on samples to link samples to a specific person. 
A key to the code linking samples to the participant will be kept in a secure MS Access database management system. This
database system will be accessible by password only by the database manager and approved study staff who have been trained in
HIPAA guidelines and requirements. The password will be provided on an as-needed basis. 
The INFORM database will house the study data. This database will include information from participants’ questionnaires, as well
as clinically relevant information (date of diagnosis, stage of disease, current treatment regimen) for subjects. Again, this database
will only be accessible to approved members of the study team. Information in the database will be identified using the same study
ID numbers placed on participants’ blood samples and surveys.
4
* Provide a plan to protect the identifiers from improper use and disclosure.
When participants enroll in the study, their name, date of birth, and CHB/BWH medical record number will be recorded alongside
their newly assigned study ID number in the Access database. This will be accessible only to certain approved members of the
study team. No one else will have access to the key or other identifying patient information. 
5
* Provide a plan for destroying the identifiers at the earliest opportunity consistent with the conduct of the research or
provide a health or research justification for retaining the identifiers. For protocols that may be subject to future
continuing and secondary data analysis, the IRB highly recommends providing justification for not destroying identifiers
permanently.
When samples are collected from participants, samples will immediately be deidentified from the patient and will be identified by
the participant's study ID number and not with name or DOB. The visit date will be placed on the sample to prevent errors in


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specimen processing or handling, since participants will be coming for more than one visit. Similarly, surveys will only be marked
with the participant's study ID number. 
The information gathered in this pilot study will serve as important preliminary data for researchers studying endometriosis, and will
go on to inform future larger randomized trials. Because this research gains strength and depth as the number of patients
increases, there is no immediate plan to destroy the master list which will tie data/samples to patient identifying information.
6
* Will a certificate of confidentiality be obtained for this research? 
  Yes No
If YES:
6.1 Please upload certificate, if available. 
Name
Date Last Modified
Version
Owner
There are no items to display
6.2
Check here if certificate is pending and will be submitted via an amendment at a later date.
 
Protected Health Information and HIPAA Authorization Information
Protected Health Information (PHI) is information acquired by Children's Hospital, including
demographic information, that could reasonably identify an individual AND:
        
Relate to the past, present, or future physical or mental health, condition or treatment of an
individual; OR
        
Describe the past, present, or future payment for the provision of healthcare to an individual.
There are some limited situations when research protocols will not use or create protected health
information. For example, educational research conducted in a school setting.
1
*The following information is considered identifiable PHI under the Privacy Rules regulations.
Indicate which of the following will be obtained.

Patient/Subject Name or the names of relatives, employers, or household members

Medical record numbers (or specimen #)

Address street location

Address town or city *

Address state*

Address zip code*

Elements of Dates (except year) related to an individual. For example date of birth,
admission or discharge dates, date of death, dates of procedures*

Telephone number

Fax Number

Electronic mail (email) address

Social security number

Health plan beneficiary numbers

Account numbers

Certificate/license numbers

Vehicle identification numbers and serial numbers including license plates

Medical device identifiers and serial numbers

Web URLs

Internet protocol (IP) address


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
Biometric identifiers (finger and voice prints)

Full face photographic images

Any unique identifying number, characteristic or code
 NONE OF THE ABOVE: this protocol will not use any identifiable PHI  
 *  These items may be included and considered a “limited data set”. Use of data under the provisions
of a “limited data set” require the signing of a data use agreement by the recipient (this includes
researchers).
 
Protected Health Information and HIPAA Authorization Information - Continued
1
Please check all of the categories that indicate where a research subject’s PHI may be disclosed.
For this purpose, "disclosure" means release, transfer, provision of access, or otherwise divulging
protected health information outside the entity initially acquiring the information as specified in the
protocol; most often that will be Children's Hospital Boston.
Internal at Children's Hospital
Data Safety Monitoring Committee
Food and Drug Administration (FDA)
Other health care providers of subject
Third Party Payers - if third parties are billed for procedures performed during research
Sponsor of Trial
Contract Research Organization (CRO): organizations contracted to perform portions of the study (i.e.,
screening, data collection)
Specify the name/organization.
Collaborator
Specify who and the location. 
Brigham and Women's Hospital
Cooperative Group/Network 
Specify the name of the network/group. 
Boston Center for Endometriosis
Other
Specify who and the location. 
 
Data and Safety Monitoring
All protocols that present greater than minimal risk require a data and safety monitoring plan(DSMP).
Investigators may also choose to submit a plan for any protocol.
1
* Please check one of the three categories. 
This protocol is greater than minimal risk and therefore requires a DSMP (responses to all
questions below are required).
This research is minimal risk but we have included a DSMP (respond to the questions below that apply to
your DSMP).
This protocol is minimal risk and we are not including a DSMP (do not respond to the questions below).
2
Which individual or group will be responsible for monitoring the data and safety for this study?
Principal Investigator/Research Team
Independent Monitor(s)
Internal Committee at the Hospital


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Data and Safety Monitoring Board (DSMB) or Data Safety Committee (DSC) Independent of PI and
Sponsor
Data and Safety Monitoring Board (DSMB) or Data Safety Committee (DSC) Not Independent of PI and
Sponsor
Other 
Specify:
3
Provide a description of the individuals who will be responsible for data safety monitoring, including
the following details: 
(1) association with the research or study sponsor; 
(2) nature of expertise and; 
(3) whether they are independent of the commercial sponsor. 
If those monitoring the study are not independent of the sponsor, please describe how any potential
conflicts of interest or biases will be avoided.
1. The following co-investigators will be responsible for data safety monitoring: Drs. Amy DiVasta, Mark
Hornstein, and Stacey Missmer. In addition, Dr. Raymond Anchan will serve as an independent monitor.
2. Drs. DiVasta and Hornstein have successfully conducted multiple clinical trials involving recruitment of
research subjects from CHB and BWH. Dr. Missmer is an experienced epidemiologist with expertise in the field
of endometriosis, and will be essential in thoughtful analysis of the data and any adverse events. Dr Anchan is
an experienced obstetrician/gynecologist and researcher at BWH. 
3. We have no commercial sponsor, so no conflict of interest or bias will occur.
4. Oversight will also occur from the BCH CTSU Monitoring Group. 
Note: If this information is in the protocol, please specify where (by the section number) the relevant
information can be located. 
4
What data will be reviewed?

Adverse events/Unanticipated problem

Aggregate data

Enrollment numbers

Individual subject data/case report forms

Protocol violations/deviations

Subject withdrawals/terminations

Other
Specify:
5
How often will data and safety monitoring be performed? Please specify if this is a specific number of
times, at defined time points, after a certain number of subjects have been recruited or as needed (i.e.
every 6 months, every SAE, every 5 subjects, etc.). If this information is in protocol, please specify
where relevant information is located.
As every 3rd subject is enrolled, or as needed/immediately for any serious adverse event.
6
Describe the responsibilities that have been given to the data and safety monitoring function. This
should include a discussion of whether the data and safety monitoring plan includes a charter, whether
stopping rules will be developed, and if any interim analysis will be performed (if so, on what basis). If
this information is in protocol, please specify where relevant information is located.
Risks of this study are low, but greater than minimal risk, due to the fact that the medications to be used
have minimal potential side effects and will be given in traditionally accepted/clinically utilized doses 
Given that this is a small pilot study with somewhat subjective outcomes, aggregate unblinded data will not be
reviewed by the DSMB for fear of introducing bias. Potential side effects of the medications will be reviewed at
each study visit by the research coordinator, and laboratory data obtained, looking for any significant safety
issues. Any concerns regarding side effects of the medication, or any laboratory values outside of the expected
range, will be brought to the attention of the PI by the research coordinator immediately.
7
If this protocol is for a multicenter trial what mechanisms are in place to either receive or distribute
results of the data and safety monitoring function in a prompt manner.
The protocol will be conducted at BWH and CHB. The same investigator group is overseeing and running
the trial at both institutions, so dissemination of data and results will be seemless. The monitoring group will
have access to all data, regardless of at which institution the subject is seen.


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8
If a DSM charter exists, please upload it.
 DiVasta Monitoring Plan.Signed.03.31.17.pdf
3/31/2017 11:58 AM
0.02
Amy DiVasta
 MONITORING SOP.Signed.03.31.17.pdf
3/31/2017 11:58 AM
0.02
Amy DiVasta
 
Risks and Benefits
Risks
1
* Provide a description of the foreseeable risks to subjects. Consider all types of risks,
including physical, psychological, social/reputation, legal, financial, privacy and breach of a
promise of confidentiality. 
The potential risks and discomforts include a bruise at the site of venipuncture (for subjects electing
to provide a blood sample); infection resulting from venipuncture is also a risk, albeit very rare. Subjects
may also experience discomfort when asked sensitive questions about their lifestyle as part of the
questionnaire. 
Another potential risk to participation would be a breach of confidentiality. In order to minimize this risk,
all samples are stored with a code number unique to each participant. Samples will not be labeled with
any type of identifying information such as name or medical record number. All health information is also
de-identified, and labeled only with the code number. All data are kept in a secured server, in files that
are password protected. Only authorized personnel within the Boston Center for Endometriosis will have
access to identifying information. If samples are shared with researchers, they will be identified only by
the unique code number and possibly by non-identifying information such as age, race, or ethnicity.
Samples will not be sold for profit. If results of tests performed on the specimens are ever published in
the medical literature, no identifying information will be included. The results of the tests performed for
research purposes will not be placed in the medical record. A copy of the consent form will not be
placed in the medical record. In this manner it will be unlikely that others within the hospital, an
insurance company or employer would ever learn of such results.
Risks of the medications to be given in this study are low when eligibility criteria are met, as described
below:
Norethindrone acetate is a synthetic hormone, which will be given to subjects at physiological doses.
Thus, we do not anticipate adverse events associated with use of the medication. In the numerous
studies of adult women with endometriosis to whom norethindrone acetate was given, no significant
adverse events were reported. Side effects could include: weight changes, edema, acne, headache, or
change in mood. We will assess for these side effects with repeated physical examinations and the self-
administered assessments, the SF-36, Beck Depression Inventory, the pain measures, and the MRS.
The safety of cabergoline has been evaluated in approximately 1,200 patients with Parkinson’s disease
in controlled and uncontrolled studies at dosages of up to 11.5 mg/day which greatly exceeds the
maximum recommended dosage of cabergoline for hyperprolactinemic disorders, and the dosage used
in the proposed pilot study. When used in similar populations of reproductive aged women for other
indications, at doses identical to those proposed in the current study, cabergoline side effects include: GI
distress (constipation, pain), dizziness, headache, tingling, or swelling of the extremities. In addition to
the adverse events that occurred in the patients with hyperprolactinemic disorders, the most common
adverse events in patients with Parkinson’s disease (and treated with doses of ~3 mg/day) were
dyskinesia, hallucinations, confusion, and peripheral edema. Heart failure, pleural effusion, pulmonary
fibrosis, and gastric or duodenal ulcer occurred rarely. Postmarketing cases of cardiac valvulopathy
have been reported in patients receiving cabergoline. These cases have generally occurred during
administration of high doses of cabergoline (>2mg/day) for the treatment of Parkinson’s disease. 
No significantly increased risk of clinically relevant cardiac valve disorders was found in subjects treated
with long-term cabergoline therapy at the doses used in endocrine practice. Current expert
recommendations state that patients prescribed cabergoline should be screened by a clinical
cardiovascular examination and that echocardiogram should be reserved for those patients with an
audible murmur, those treated for more than 5 years at a dose of more than 3 mg per week, or those
who maintain cabergoline treatment after the age of 50 years.
Erythrocyte sedimentation rate (ESR) has been found to be abnormally increased in association with
pleural effusion/fibrosis. We will utilize a measurement of ESR at each study visit to screen for the very
unlikely development of a fibrotic disorder associated with low-dose cabergoline use. If we find that the
ESR increases to abnormal levels, a clinical evaluation would be indicated, including a chest x-ray.
Serum creatinine measurements can also be used to help in the diagnosis of fibrotic disorder, and will
be checked at each visit.
The effects of the study drugs on the reproductive system (sperm, eggs) or to the developing fetus are
not well understood. Norethindrone acetate is labeled by the drug manufacturer as "contraindicated
during pregnancy". Of note, norethindrone (another first generation progestin) 0.35 mg PO daily is FDA
approved and marketed as an effective method of birth control. In our study, patients randomized to


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norethindrone acetate will receive 5 mg po daily. Cabergoline has no known effect on pregnancy, based
upon animal reproductive studies, and is approved for use during pregnancy "if needed". For these
reasons, a pregnancy test will be performed at each visit. Women who become pregnant during the
study would be terminated from further study participation. For this reason, participants taking the drug
should not become pregnant. To be a part of the research, participants will be advised that they must not
have sexual intercourse or must use reliable, effective birth control during participation. 
During research visits, participants may be asked questions that lead to feelings of discomfort,
emotional upset, or frustration. Participants will be advised that they may not be able to answer all the
questions and do not need to answer any questions that they do not wish to answer. If the participant
were to become distressed, the Principal Investigator will be notified by the Research Coordinator. We
will offer to have the participant speak to a mental health professional regarding her feelings. The Beck
Depression Inventory-II will be scored by the Research Coordinator during the study visit, while the
participant is still present. It is possible that the study team could identify concerns for depression from
the answers to the questionnaires. If the participant has a score ≥ 20 (indicating moderate or severe
depression) or responds anything other than 0 to Item 9 (I don’t have any thoughts of killing myself), the
Research Coordinator will alert the Principal Investigator immediately. The study team will notify the
participant regarding our findings from the Depression Inventory, and encourage the participant to allow
us to share the information with her parent (if she is age<18 years) or her healthcare provider.
Additionally, mental health resources will be made available to the participant. Participants are informed
within the consent form that “If, during your participation in this research, there is reason to believe that
you are at risk for being suicidal or otherwise harming yourself or others, the research team is required
by law and Hospital policy to act on this suspicion. This may include notifying your parent (if you are
age<18), your therapist(s) if applicable, or other individuals. If you are
2
* What is the likelihood and seriousness of such risks?
The likelihood of such risks is low, and no serious risks are anticipated.
3
* Describe provisions for minimizing risks to participants.
Subjects are monitored closely throughout the course of participation by both the study team, and
with their clinical care gynecology provider. 
At the baseline study visit, we will measure blood samples for total cholesterol, HDL cholesterol, and
triglyceride levels. This lipid profile will allow us to monitor for any individual changes in serum lipids
from baseline, and for differences between treatment groups. In some studies of adult women, mildly
deleterious effects on circulating lipid profiles have been seen in patients receiving treatment with
norethindrone acetate (decreased HDL). Lipid profiles will be repeated at follow-up visits scheduled for 3
and 6 months after initiation of therapy. Blood samples will also be taken for liver function tests (AST,
ALT) at each visit to allow us to monitor for any liver inflammation associated with the drug therapy.
HbA1c will be taken at baseline and at 6 months to monitor for impairments in glucose metabolism. We
will utilize a measurement of ESR and serum creatinine at each study visit to screen for the very unlikely
development of a fibrotic disorder associated with low-dose cabergoline use. A physical examination will
be performed at each visit to assess for acne, and cardiac auscultation will be done to assess for the
presence of a cardiac murmur. The presence or absence of hormonal symptoms (mood changes, breast
tenderness, acne, and changes in menstrual bleeding patterns) will be queried at each visit. The
hormonal milieu will be assessed using serum measurements of estradiol and prolactin at baseline and
each subsequent study visit. These laboratory studies will allow us to monitor cabergoline activity, and to
determine compliance with cabergoline treatment in Group 2. If any cardiac murmur is identified during
study participation, an echocardiogram will be performed. 
Subjects will be discontinued from further study participation if any of the conditions that are listed as
exclusion criteria for participation develop during the six months of active participation in the study.
Because of the potential risk of adverse side effects, patients in the treatment trial will be monitored
closely during the 6-month study period with laboratory assessments and physical examinations every
three months. 
Study participants will be able to contact one of the study physicians at any time if questions or concerns
arise. No confidential information from this study or other data within a patient’s medical record may be
furnished to anyone unaffiliated with Children’s Hospital without written consent, except as required by
law or regulatory agencies (e.g., FDA).
All participants will be advised to abstain from sexual intercourse, or to use reliable birth control to
prevent pregnancy. A pregnancy test will be performed at each of the 3 study visits. 
Potential Benefits
4
* Are there potential direct benefits to the research participants?
  Yes No
If YES:
4.1 Describe the potential direct benefits to the research participants.
The medications used will be provided to the patient at no cost, and will potentially ameliorate


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ongoing endometriosis-associated pain. Participants will be given information about their results to
share with their primary care provider, including monitoring of lipid panels, liver function, and
hormonal status.
5
* Describe how the research may result in knowledge expected to benefit society.
With the information gathered from the proposed study, we hope to develop evidence-based
guidelines for the utilization of norethindrone acetate and/or cabergoline for treatment of endometriosis.
This study has the potential to benefit a large number of patients who suffer from endometriosis.
 
Pediatric Risk/Benefit Determination
All protocols that include children/adolescents must be classified into a risk/benefit category.
Does your study involve more than one risk/benefit category for different groups? If so, answer
questions 1, 1.1, 1.2 and 1.3 to describe the least favorable risk/benefit scenario, and use the
questions 2, 2.1, 2.2, 2.3, 2.4 to explain the risk/benefit assessment for the other groups of subjects in
your study.
“Minimal risk” means that the probability and magnitude of harm or discomfort anticipated in the
research are not greater in and of themselves than those ordinarily encountered in daily life or during
the performance of routine physical or psychological examinations or tests.
1
* Check the category below that best represents the degree of risk and benefit which children in this
study will be exposed to. If your study involves more than one group of subjects ( eg. .experimental
and placebo groups) consider whether the research presents a different risk/benefit assessment for
each group. If this is the case select the least favorable risk/benefit ratio that might apply to any of the
subjects. 
For example, a study may present  greater than minimal risk with potential for direct benefit for  an
experimental group, but no potential for direct benefit for a placebo group. In this case you should
select  “Greater than Minimal Risk; No Potential for Direct Benefit” in this section and use section 2
below to describe the risks and benefits for the group for which there a potential for benefit.
No more than Minimal Risk; Potential for Direct Benefit
No more than Minimal Risk; No Potential for Direct Benefit
Greater than Minimal Risk; Potential for Direct Benefit
Greater than Minimal Risk; No Potential for Direct Benefit, but likely to yield generalizable knowledge
about the subject’s condition
1.1 If Greater than Minimal Risk; Potential for Direct Benefit
1.1.1 How is the risk justified by the benefit?
The medications used will be provided to the patient at no cost, and will potentially ameliorate
ongoing endometriosis-associated pain. Participants will be given information about their results
to share with their primary care provider, including monitoring of lipid panels, liver function, and
hormonal status. Both medications are commonly used in the reproductive-aged group of
females that we are recruiting for the current study.
1.1.2 How is the benefit to risk assessment at least as favorable as presented by alternative
approaches?
No patient is denied treatment, or receives only placebo therapy. We are recruiting patients
who remain in pain from their endometriosis with the hope of identifying a novel therapy to
ameliorate symptoms. The two medications are frequently used within this age group.
1.2 If Greater than Minimal Risk; No Potential for Direct Benefit 
1.2.1 How is the risk of the protocol a minor increase over minimal risk?
1.2.2 How do the procedures present experiences to the subjects that are reasonably
commensurate with those inherent in the subjects’ actual or expected situations? 
1.2.3 How is knowledge to be gained of vital importance for the understanding or amelioration
of the condition?
1.2.4 Can the consent of both parents be obtained if reasonably available?
1.3 To which group of subjects does this risk/benefit assessment apply?
All subjects 15-40 years of age who will be recruited for study participation.


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2
* Does your protocol have more than one risk/benefit group?
  Yes No
If YES:
2.1 Check the category below that best represents the degree of risk and benefit which children in
this study will be exposed to.
No more than Minimal Risk; Potential for Direct Benefit
No more than Minimal Risk; No Potential for Direct Benefit
Greater than Minimal Risk; Potential for Direct Benefit
Greater than Minimal Risk; No Potential for Direct Benefit, but likely to yield generalizable
knowledge about the subject’s condition
2.2 If Greater than Minimal Risk; Potential for Direct Benefit
2.2.1 How is the risk justified by the benefit?
2.2.2 How is the benefit to risk assessment at least as favorable as presented by alternative
approaches?
2.3 If Greater than Minimal Risk; No Potential for Direct Benefit 
2.3.1 How is the risk of the protocol a minor increase over minimal risk?
2.3.2 How do the procedures present experiences to the subjects that are reasonably
commensurate with those inherent in the subjects’ actual or expected situations? 
2.3.3 How is knowledge to be gained of vital importance for the understanding or amelioration
of the condition?
2.3.4 Can the consent of both parents be obtained if reasonably available?
2.4 To which group of subjects does this risk/benefit assessment apply?
 
Non-Genetic Incidental Findings and Dissemination of Research Results
Non-Genetic Incidental Findings 
This section addresses incidental findings that are not genetic. Genetic incidental findings and return of genetic
results are addressed in the “Genetic Research Results” section.
1
* Is there a possibility of clinically significant non-genetic incidental findings being discovered during the
research study?  These may include the unexpected discovery of abnormal results following an MRI of a
healthy control, or indications of subject depression following review of quality of life assessments etc. This
should also be explained in the consent form.
  Yes No 
IF YES:
1.1 Please describe any potential non-genetic incidental findings that may result from the
study.
Mental Health surveys that will be administered during the pilot study include the Beck
Depression Inventory-II. This is an updated version of a validated measure which has been widely
used in studies of adolescents, and is validated for use in persons aged 13-80 y. It is possible that
subject depression may be uncovered after review of these assessments.
It is also possible that a previously unidentified cardiac murmur will be identified during the study.
1.2 Outline the plan for addressing non-genetic incidental findings (e.g., contacting the
participant’s primary care provider, referral, etc.). 
This scale will be scored and screened at the time of the subjects’ study visits. Any subject who
reports a moderate level of depressive symptoms or higher (defined as a Beck Depression Index-II
score ≥20) or who circles a response other than “0” to question 9 (which addresses suicidal
ideation) will be referred to a mental health provider or their medical provider at the time of the
study visit according to standard clinical practice. 
If a cardiac murmur is identified, the patient will be notified. We will also notify the patient's medical
provider with permission.


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Dissemination of Non-Genetic Results
Research subjects express the desire to receive information about study progress as well as aggregate or individual
results. In addition, subjects appreciate being acknowledged for their participation. As part of our ongoing efforts to
recognize the efforts and partnership with research subjects, investigators are asked to take whatever steps possible
to acknowledge subjects for their participation and, when appropriate, to provide individual and aggregate results.
Although it is not always possible to provide results within a defined period of time (sometimes for years), it may be
possible to provide research subjects with periodic updates or, in certain circumstances, to inform subjects about the
progress of the research in lieu of actual results. Please complete the following questions as they apply to your
research. All investigators are expected to acknowledge subjects’ participation and, when appropriate, to provide
results. We ask that investigators take steps beyond only providing results if a subject/family requests it.
2
* Will this research produce individual results for research participants?
  Yes No 
If YES:
2.1 Will this research produce individual genetic results to research participants?
  Yes No
IF YES: Please complete the Section on Genetic Research Results Return.
2.2 Will you be able to produce individual non-genetic results to research participants?
  Yes No 
If YES:
2.2.1 What types of results will you provide? How will you provide the results? When will you
provide the result?
Subjects will have access to their clinically relevant laboratory results, such as lipid labs.
These results will be provided to the patient within 1-2 weeks after each study visit.
2.2.2 Will you give participants an option (opt-in or opt-out) to receive these results?
If NO:
2.3 Please explain why you will not provide individual results to families.
Dissemination of Aggregate Results
3
* Will you be able to provide aggregate results to participants?
  Yes No 
If NO:
3.1 Please explain why you will not provide aggregate results.
If YES:
3.2 When will you provide aggregate results and how will they be provided?
Aggregate results will be available to participants after all participants have completed the trial, and analysis
has been performed on the data.  
 
3.2.1 What format will you use to provide aggregate results to families? ( check all that apply) 
Letter to all participants
Copies of peer focused publications, upon subject/family request
 
If Other:
3.2.1.1 Please describe.
4
If it is not possible to provide either individual or aggregate results (e.g., biorepository protocols), what steps
will you take to thank participants and advise them about the progress of the study? For example, some
investigators will provide a thank you letter and develop newsletters or website that participants may learn
about the progress of the research in general .
 
Research Categories and Special Considerations
1
Please select the appropriate research category for your research. A primary category must be selected. A secondary
category should be selected only if applicable. 


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* Primary Research Categories:
Intervention/Trial Therapeutic ( e.g. drugs, devices, comparison of therapeutic approaches, new procedures)
Intervention/Trial Non-Therapeutic (extra ECHO, MRI, physical exams for non-therapeutic purposes)
Behavioral/Psychosocial Interventions/Trials
Establishment of Specimen Repository
Epidemiology/Observational Study – e.g. survey, case/control/data registries, cohort studies
Quality Improvement
Lab Specimen Studies – e.g. blood, urine, extra tissue during biopsy, genetic research
Educational/Training – e.g. training of residents or other professional staff
Secondary Research Categories:
Intervention/Trial Therapeutic ( e.g. drugs, devices, comparison of therapeutic approaches, new procedures)
Intervention/Trial Non-Therapeutic (extra ECHO, MRI, physical exams for non-therapeutic purposes)
Behavioral/Psychosocial Interventions/Trials
Establishment of Specimen Repository
Epidemiology/Observational Study – e.g. survey, case/control/data registries, cohort studies
Quality Improvement
Lab Specimen Studies – e.g. blood, urine, extra tissue during biopsy, genetic research
Educational/Training – e.g. training of residents or other professional staff
2
Please check all of the following that apply to the proposed research.
This protocol involves the use of a drug, biologic, nutritional supplement, herbal or homeopathic medicine, medical food, medical
gas, inhalation therapy, topical cream, chemical or other compound that will be administered as the object of the protocol or
because it is relevant to the aims of the research protocol.
This protocol involves a device that will be used, administered, implanted, or applied to the subjects, as the object of the protocol
or is relevant to the objectives of the protocol. This includes investigational devices classified as both significant risk and non-
significant risk as well as FDA approved/marketed devices.
This protocol involves the collection and use of material for genetic studies or creation of IPS lines as part of this current study
and/or for potential genetic studies in the future.
This protocol involves the use of a placebo.
This protocol includes an imaging exam or procedure to be done in Radiology or Nuclear Medicine for research purposes.
Please contact Simon Warfield (Simon.Warfield@childrens.harvard.edu) and Samantha Taylor
(Samantha.Taylor@childrens.harvard.edu) . Simon and Samantha will collect some additional information from you and
coordinate the review of the information through Radiology to assure that the imaging protocol can be performed, the correct
charges have been established and that Radiology will be able to accommodate the study in the imaging schedule. You will not
be able to have imaging performed without this. It is imperative that you contact Simon or Samantha immediately.
This protocol requires for research purposes 1) radiological assessments and procedures that  involve radiation exposure ( X-
ray, CT, PET scans) or 2) nuclear medicine procedures (imaging or therapeutic). ( Do not check this category if these 
procedures and assessments will  be performed as part of clinical care).**
This protocol requires for research purposes MRI scans (Do not check this category if these procedures and assessments will 
be performed as part of clinical care).**
This protocol involves the establishment of a human biological specimen repository. Repositories are defined as prospective
collections of specimens that are processed, stored and distributed to multiple investigators for use in research.
This protocol involves the collection of a tissue removed for clinical purposes that would routinely go to pathology.
This protocol acquires fetal biospecimens (this includes specimens taken from pregnant women or acquisition of fetal tissue
obtained from terminations).  
If fetal tissue from terminations are proposed please be sure to include in your protocol document or smartform detailed
information about where it is acquired from and how it will be used. In addition, submit copy of IRB approvals from sites where
the tissue was actually obtained.
This protocol includes an intervention with human subjects that involves either 
a) the derivation of stem cells from embryos or, 
b) the implantation of stem cells obtained from fetal tissue or embryos.


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This protocol includes research that is conducted at a non US location.
Please check this off if you are conducting international research but be aware that these questions do not apply to multi-site
studies that are also multi-national. 
This protocol involves collection of blood samples other than discarded specimens.
This protocol involves the use of a device that emits laser radiation.
Please check this off if you are using QoL measures or other surveys, questionnaires, etc. which may yield incidental findings
requiring intervention for depression, anxiety, suicidal/homicidal ideation, domestic violence, child maltreatment or other acute
safety concerns. Also, check this if you have included a Social Worker among the Research Team.
** This must be selected if the protocol involves imaging, regardless of where the imaging may occur.
 
Nursing/Biosafety/Gene and Cellular Therapy
1
*  Will this protocol require any of the following nursing services for any research related direct care
requirements?
  Yes No
If YES:
1.1 Check all that apply:

Assessment of physical/mental status of subjects

Monitoring requirement non invasive

Monitoring requirement invasive

Additional intravenous requirements

Collection of blood and specimens

Frequent timed lab draws

Accompany patients to test areas

Patient/family education, including self and home care

Administration of investigational drugs and other substances

Use of new technology/equipment in study protocol

Symptom management/intervention

Constant supervision

Requirements from other services that require nursing coordinator
1.2 Specify required services. 
Blood draw, height/weight and vital signs, urine pregnancy test, distribution of study medications
2
* Does your study involve the administration of any of the following to a human research participant?
  Yes No 
If YES:
2.1 Please check all that apply.

Genetically-modified cells or seek to genetically modify patient tissues in vivo using
recombinant or synthetic nucleic acid molecules (natural-derived or synthesized DNA or
RNA)

A cellular or biologic product that involves complex manufacturing (e.g. cell culture or cell
selection in a GLP/GMP facility, outside the operating room)

Biological agents or material containing biological agents. Biological agents include bacteria,
viruses, parasites, rickettsia, fungi, prions and toxins of biological origin regardless of
pathogenicity to humans (e.g. fecal microbiota transplantations, oncolytic viruses)

Xenotransplantation (cells, tissues or organs from a nonhuman animal source or have come
into contact with nonhuman sources)
NOTE: Please note if the first or second option is checked, the protocol will be routed to a specialized
institutional scientific review committee and will not be sent for your own departmental scientific reviewers.
If option "Genetically-modified cells or seek to genetically modify patient tissues in vivo using


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recombinant or synthetic nucleic acid molecules (natural-derived or synthesized DNA or RNA)" was
selected, please check off as applicable for this research and answer the associated questions:
2.1.1  The protocol uses a new vector, genetic material, or delivery methodology that represents a
first-in-human experience, thus presenting an unknown risk. 
  Yes No
2.1.1.1 If Yes, please describe vector, genetic material, and delivery method and what may be
known about any associated risks.
2.1.1.2 If No, please indicate the section or location in the protocol where the vector, genetic
material or delivery methodologies risks are clearly described based on previous
experience in human studies.
2.1.2 The protocol relies on preclinical safety data that were obtained using a new preclinical model
system of unknown and unconfirmed value. 
  Yes No
2.1.2.1 If Yes, please describe the new preclinical model system of unknown and unconfirmed
value.
2.1.2.2 If No, please explain why this is not a preclinical model system of unknown and
unconfirmed value.
2.1.3 The proposed vector, gene construct, or method of delivery is associated with possible toxicities
that are not widely known and that may render it difficult for oversight bodies (IRB, IBC) to
evaluate the protocol rigorously. 
  Yes No
2.1.3.1 If Yes, please describe why the possible toxicities are not widely known and may render
it difficult for oversight bodies (IRB, IBC) to evaluate the protocol rigorously.
2.1.3.2 If No, please justify that the possible toxicities are widely known and oversight bodies
(IRB, IBC) will be able to evaluate the protocol rigorously.
 
Protocol and Appendices
* All investigators must submit an experimental design and protocol with the CHeRP
submission. If there is a protocol from a corporate sponsor or cooperative group available and it
contains the following necessary elements you may attach that. For investigator initiated
research a link to a protocol outline that may be completed and attached may be found at:
CHeRP Protocol Outline 
1
Upload Protocol - please be sure the protocol includes the following sections.  
Specific Aims/Objectives
Background and Significance
Preliminary Studies
Design and Methods
Study Design
Patient Selection and Inclusion/Exclusion Criteria
Description of Study Treatments or Exposures/Predictors
Definition of Primary and Secondary Outcomes/Endpoints
Data Collection Methods, Assessments, Interventions and Schedule (what assessments
performed, how often)
Study Timeline (as applicable)
Adverse Event Criteria and Reporting Procedures
Data Management Methods
Quality Control Method
Data Analysis Plan
Statistical Power and Sample Considerations
Study Organization
References
Upload protocol
Name
Date Last Modified
Version
Owner
 Cabergoline protocol
3/31/2017 11:28 AM
0.22
Amy DiVasta


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2
Appendix Materials:
2.1 Survey, questionnaires, assessments
Name
Date Last
Modified
Version Owner
 Appendix A.VAS.PNG
6/15/2015 12:37
PM
0.01
Amy DiVasta
 Appendix B.Biberoglu and Behrman Score.docx
6/15/2015 12:38
PM
0.01
Amy DiVasta
 Appendix C.BPI-SF_English-
24h_Original_CURRENT.pdf
6/15/2015 12:38
PM
0.01
Amy DiVasta
 Appendix D.Beck.doc
6/15/2015 12:38
PM
0.01
Amy DiVasta
 Appendix E.PGIC_scale.pdf
6/15/2015 12:39
PM
0.01
Amy DiVasta
 Appendix F.SF 12.pdf
12/9/2015 11:26
AM
0.02
Amy DiVasta
 Appendix G.NSSSS.PNG
6/15/2015 12:39
PM
0.01
Amy DiVasta
 Appendix T: Symptom checklist
3/31/2017 11:24
AM
0.02
Amy DiVasta
 FDI
12/9/2015 11:27
AM
0.01
Jenny
Gallagher
2.2 Flow charts, schemas
Name
Date Last Modified
Version
Owner
There are no items to display
2.3 Other
Name
Date Last Modified
Version
Owner
 Med teach form
12/23/2015 10:16 AM
0.02
Jenny Gallagher
 Provider letter
2/25/2016 3:06 PM
0.01
Jenny Gallagher
 Test results letter
2/25/2016 3:11 PM
0.01
Jenny Gallagher
 
Method of Consent
1
* Check all that apply:
Please note that if a waiver of parental permission is requested, both “written informed
consent/assent/authorization will be obtained from subjects” and “waiver of parental permission
is requested” should be selected.

Written informed consent/assent/authorization will be obtained from subjects.

Informed consent/assent/authorization will be obtained through a method other than a written
document (i.e. verbal, survey completion).

*Waiver of informed consent and authorization are requested. No consent/authorization will be
obtained.

*Waiver of parental permission is requested.

Other method.
Please explain any other method of consent or issue you want the IRB to review regarding
consent and assent.
* Please note that this option cannot be applied to FDA regulated research.
 
Written Consent


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1
* Who will obtain informed consent/assent/authorization?
A trained and IRB-approved member of the study team (PI or study coordinator) will obtain informed
consent.
2
* When and where will informed consent/assent/authorization be obtained?
Consent will be obtained either at the time of recruitment or at the time of the initial study visit. Informed
consent will be obtained in the Adolescent Clinic or Gynecology Clinic at CHB or BWH, in a private setting, or
within the Research space of the CTSU.
3
* Please indicate whether the children in this study are generally capable of providing assent. 
Take into account the ages, maturity and psychological state of the children involved.
All are capable.
Some are capable.
None are capable.
N/A - only adults will be enrolled
3.1 * Explain your selection:
Eligible subjects are at least 15 years of age and will be able to provide assent or consent as
appropriate.
4
If applicable, describe the process that will be used to obtain the child’s assent.
Pediatric patients will be involved in the consent discussion with the parent. The study team member will
assess the adolescent's understanding of the study and will provide time for questions and consideration of
the study.
5
* How will you assure that the subject has adequate time to decide whether or not they want to
participate?
The consent form will be reviewed section by section with the potential participant. The study coordinator
will allow and encourage questions to be asked at any point during the consent process. The study
coordinator will give the potential subject time to ponder participation. An interested patient may choose to
participate at a future clinical visit after thinking more about the matter privately.
6
* How will you determine that the parent and/or child understand the elements required in the
informed consent/assent/authorization process?
In addition to providing sufficient time for the patient to thoroughly read the consent form, the person
consenting will talk them through each portion of the consent. After each section is covered, the PI/RA will
solicit questions before moving forward.
7
* Could children reach the age of majority while still actively involved in the protocol?
  Yes No
If YES, consent is required from the now adult, unless the committee grants a waiver of consent. Please
answer one of the following two questions (7.1 or 7.2). You may also answer both if both apply. 
7.1 Please specify how you plan to obtain consent when a subject turns 18.
If a subject turns 18 while actively enrolled in the six month trial, consent will be obtained at the next
research visit, before any procedures take place.
7.2 If you are requesting a waiver of consent when the child turns 18, address each of the following
regulatory requirements to obtain a waiver of informed consent. All criteria need to be met in order for a
waiver to be granted.
7.2.1 Explain why the research could not practicably be conducted without access to and use
of the identifiable health information/data.
7.2.2 Explain why the research involves no more than minimal risk to subjects.
7.2.3 Explain why the research could not practicably be conducted without the waiver of
informed consent and authorization.
7.2.4 Explain why the waiver of consent/authorization will not adversely affect the rights and
welfare of the individuals.
  8
* Will any of the children originally enrolled in the study reach the age of majority and not have the
ability to provide consent when they turn 18 because of decisional impairment?


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  Yes No
Please Note once a child reaches the age of 18 they must consent for themselves. For children with decisional
impairment once they reach 18, a parent must apply for and be granted the legal ability to continue to serve as a
legally authorized representative. Otherwise the IRB must approve for others to be able to provide surrogate
consent.
If YES, please respond to the following questions:
8.1  Describe the criteria and /procedures or measurements for evaluating the decisional status
of the now adult subject to determine whether they are capable of consenting on their own
behalf. This would include the use of standardized measurements, consults with another
qualified professional, etc.
8.2 Describe how you will determine who is authorized to provide legally valid consent for the
now adult subject. This could include use of durable power of attorney for healthcare, a
legally appointed guardian (this must be a court-appointed induvidual), or the use of
surrogate consent as approved in IRB. Please include whether and how legal records
regarding authority will be obtained and reviewed by the research team.
 
8.3 When possible if legally effective consent cannot be obtained from the now adult subject,
assent should be obtained. Please describe if you plan to obtain assent and provide criteria
used to evaluate the assent or dissent of the now adult sibject with decional impairment
 
9
* Regulations require that significant new findings developed during the course of the research, which
may relate to the subject's willingness to continue participation, be provided to the subject. Describe
how this requirement will be met.
If significant new findings develop, this information will be disseminated to all participants. The consent
forms will also be amended to reflect any change in the risk/benefit ratio of the study.
10
* Upload all consent and assent forms. If there is more than one, list the titles or categories of each
form submitted (e.g. experimental, control, sub-study). 
Name
Date Last Modified
Version
Owner
  
Cabergoline consent
3/31/2017 11:29 AM
0.16
Amy DiVasta
  
Cabergoline consent.03.31.17.docx
9/14/2017 9:35 AM
0.02
Theresa Williams
NOTE: Your consent must use the current required format.Click here to download the template
 
Drugs, Biologics or Other Products
Please provide information for the drug/product that will be used, administered, or applied to
the subjects as the object of the study or that is relevant to the objectives of the protocol.  If
there is more than one drug/product, please be sure to enter each drug/product.  More than
one drug/product may be entered under each category.
1
The drug/biologic/product being administered is an investigational product (not approved by
the FDA)  
 Generic Name
Type of Product
Manufacturer
There are no items to display
2
The drug/biologic/product being administered is an FDA-approved agent but used outside of
the FDA labeling in an unapproved dose, route of administration, population, disease, in
concomitant medical use, etc.
 
Generic Name
Type of Product
Manufacturer
View cabergoline
Drug
Teva Pharmaceuticals
3
The drug/biologic/product being administered is FDA approved and being administered in
accordance with approved labeling
 
Generic Name
Type of Product
Manufacturer
View norethindrone acetate
Drug
Amneal Pharmaceuticals


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4
The drugs/biologics/products being administered does not fit into any of the above
categories.
 Generic Name
Type of Product
Manufacturer
There are no items to display
5
The product being administered is a dietary supplement, herbal medicine, or medical food.
 Product Name
Type Of Product
There are no items to display
6
Select the individuals that can prescribe the drugs listed in this protocol.
Last Name
First Name
Employee ID
DiVasta
Amy
106866
 
Placebo
1
* Briefly describe the placebo (drug, device, procedure, intervention, surgery, etc.) arm used in
the study. Provide a justification for use of the placebo, including the length of subject
participation in the placebo arm. Please justify why the study cannot be conducted without the
use of the placebo. Your justification should address whether outcomes are subjective and
how use of a placebo will address this issue, if applicable.
No subjects in the proposed pilot study will be denied treatment. Subjects will be randomized to
either receive norethindrone acetate (standard care) versus cabergoline (investigational drug). 
However, since the two medications are administered on a different frequency, a placebo will be used
to maintain blinding of drug assignment to both the investigators and the subject.
If a subject is randomized to norethindrone acetate, she will receive norethindrone acetate 5 mg
tablet by mouth daily + one placebo pill by mouth twice weekly.
If a subject is randomized to cabergoline, she will receive one placebo pill by mouth daily +
cabergoline 0.5 mg tablet by mouth twice weekly. 
As a result, all subjects will take 1 pill daily and 1 pill twice weekly. This will allow both the patients
and investigators to remain blinded to group assignment.
2
* Describe any commonly used diagnostic/treatment approach(es) that will be withheld from
subjects assigned to the placebo arm of this study.  Will subjects be denied any type of
treatment or diagnostics that would be considered a current standard of care?
No subjects will receive only placebo. All subjects will receive active treatment. All subjects will
receive either the intervention medication or the standard of care.
3
* Summarize any risks to subjects in the placebo arm consequent to not receiving active
treatment for their disease or condition.
No subjects will receive only placebo. All subjects will receive active treatment.
4
* Summarize the potential benefits from participation in this protocol for subjects in the
placebo arm.
No subjects will receive only placebo. All subjects will receive active treatment.
5
If applicable, how will the condition or disease of subjects in the placebo arm of this study be
monitored compared to the monitoring associated with standard care for this
disease/condition?
No subjects will receive only placebo. All subjects will receive active treatment.
6
If applicable, what criteria will be used to determine that the participation of a subject, who
may be receiving a placebo treatment, should be discontinued due to his/her worsening
disease or condition?  
No subjects will receive only placebo. All subjects will receive active treatment.
 
Title: Novel Treatments for Endometriosis (NOTE): Dopamine Receptor Agonist Therapy for Pain Relief in
Women Suffering from Endometriosis Pilot Study
Blood Collections
1
Select the method(s) of blood collection.


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1.1 Venipuncture 
1.1.1 At time of clinically indicated procedure
1.1.2 At time specifically for research
1.2 Heel/finger/ear sticks
1.3 From catheter or heparin lock
1.4 Other 
If Other:
1.4.1 Please specify.
2
* How many individual samples will collected (not number of sticks)?  
One sample will be collected per research study visit, for a total of 3 samples over 6 months.
Note: Multiple withdrawals of blood from an indwelling venous line are to be considered  more than one collection.
3
* What is the period of time the samples will be collected (please specify in weeks or if less than weeks in
days)?  
Samples will be collected at baseline, 3 months, and 6 months.
4
* Specify the total amount of blood collected in mls.  
maximum 40mLs
5
* Will research subjects be less than 16.5 kg?
  Yes No
If YES:
5.1 Will the total amount of blood to be drawn from children less than 16.5 kg be more than 3mL/kg?
  Yes No
 
Title: Novel Treatments for Endometriosis (NOTE): Dopamine Receptor Agonist Therapy for Pain Relief in
Women Suffering from Endometriosis Pilot Study
Additional Documents
1
Please upload any additional documents if it is necessary.
Name
Date Last Modified
Version
Owner
There are no items to display
 
PI's Statement
I assure the information I obtain as part of this research (including protected health
information) will not be reused or disclosed to any other person or entity other than
those listed on this form, except as required by law or for authorized oversight of the
research project.  If at any time I want to reuse this information for other purposes or
disclose the information to other individuals or entity, I will seek approval by the
Institutional Review Board (IRB).
I assure the IRB that there are appropriate resources (funding, equipment, space,
support services) to conduct this research safely and in accordance with all required
human subject protection policies.
* The PI accepts responsibility for assuming adherence to DHHS, FDA, HIPAA and Children’s
Hospital’s regulations and policies relative to the protection of the rights and welfare of
patients/subjects participating in this study.
  Yes No
 


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Detailed Sponsor Information
1
* What is the sponsor’s name?
J WILLARD AND ALICE S MARRIOTT FOUNDATIO - 1754 
1.1 If your sponsor is not in the list, please select "Other" from the list and specify your
sponsor below.
Note: Use a '%' to conduct a wildcard search (e.g. a '%Pharm' search will return all options with 'pharma' at any place in
the name).
2
* Please select the appropriate category of funding.
Federal
State
Corporate/Industry
External Foundation
2.1 If the category of funding is "Federal", upload the grant(s) here. (Please include the scientific part. This is
a requirement for federally supported research. You need not include biosketches or financial information
here, just the description of the research.)
Name
Date Last Modified
Version
Owner
There are no items to display
3
* What will the sponsor provide? Check all that apply:
Research Funding - Committed
4
* What is sponsor’s contact name, if applicable?
Anne Gunsteens
5
* What is sponsor’s contact phone number?
301-380-3745
6
* What is sponsor address?
10400 Fernwood Rd, Dept 925, Bethesda, MD 20817
7
* What is sponsor email address?
anne.gunsteens@marriott.com
8
* Is a Clinical Trial Agreement (CTA) required?
Completed/Signed
Pending
Not Required
 
ID: VIEW46F5DA7D2D400
Name: Detailed Sponsor Information 
Detailed Sponsor Information
1
* What is the sponsor’s name?
MARRIOTT DAUGHTERS FOUNDATION - 1822 
1.1 If your sponsor is not in the list, please select "Other" from the list and specify your
sponsor below.
Note: Use a '%' to conduct a wildcard search (e.g. a '%Pharm' search will return all options with 'pharma' at any place in
the name).


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2
* Please select the appropriate category of funding.
Federal
State
Corporate/Industry
External Foundation
2.1 If the category of funding is "Federal", upload the grant(s) here. (Please include the scientific part. This is
a requirement for federally supported research. You need not include biosketches or financial information
here, just the description of the research.)
Name
Date Last Modified
Version
Owner
There are no items to display
3
* What will the sponsor provide? Check all that apply:
Research Funding - Committed
4
* What is sponsor’s contact name, if applicable?
Nancie Suzuki
5
* What is sponsor’s contact phone number?
301-380-1425
6
* What is sponsor address?
10400 Fernwood Rd, Dept 901, Bethesda, MD 20817
7
* What is sponsor email address?
nancie.suzuki@hosthotels.com
8
* Is a Clinical Trial Agreement (CTA) required?
Completed/Signed
Pending
Not Required
 
ID: VIEW46F5DA7D2D400
Name: Detailed Sponsor Information 
Use of an Approved Drug/Product for an Unapproved Indication
1
* Select the type of product that will be administered that is relevant to the aims of the research protocol.  If
there is more than one product, enter information about one product at this time.  You will be able to enter
additional products at a later time.  
Drug
Biologic
Combination
Other
If Combination:
  Please describe. Include whether it is regulated as a drug/device/biologic. What is the mode of action? 
If Other:
  Please describe:
2
*  What is the generic name or descriptor of the product?
cabergoline


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3
What, if any, is the commercial/trade name of the product?
Dostinex
4
*  Who is the manufacturer of the product?
Teva Pharmaceuticals
5
* Who is the supplier of the product? 
Teva Pharmaceuticals
6
* Briefly describe how the research use of the product departs from the FDA approved indication/labeling.  
Cabergoline will be used in the same population of patients as the FDA-approved labeling (reproductive-aged
women), but for a different indication (for endometriosis rather than for hyperprolactinemia).
7
* Describe the purpose of the evaluation (e.g. to support a new indication for the use of the drug, to support any
other significant change in the labeling or advertising for the drug, etc.).
To determine if cabergoline represents a potential safe and effective means of pain relief for women suffering from
chronic pelvic pain related to endometriosis, and to generate preliminary data for a potential larger randomized clinical
trial. We do not anticipate this pilot study will lead to any changes in labeling or indication.
8
* Is this research being conducted under an IND?
  Yes No
If YES:
8.1 Who holds the IND?
A company, organization, NIH, consortium or university.
Children’s Investigator
Other
8.2 Specify the IND number if available (if it is not available, you need to submit an amendment
to update this information when obtained).
132882
8.3 Specify the name of the IND holder.
Amy DiVasta
8.4 Upload a copy of FDA IND approval correspondence, if available.
Name
Date Last Modified
Version
Owner
 FDA go ahead email 3-13-17.docx
3/17/2017 4:13 PM
0.01
Jenny Gallagher
 FDA response to 0000.pdf
3/31/2017 11:34 AM
0.01
Amy DiVasta
 FDA Response.01.09.17.docx
3/17/2017 4:13 PM
0.02
Jenny Gallagher
 IND submission 0000.pdf
3/31/2017 11:34 AM
0.01
Amy DiVasta
 IND submission 0001.pdf
3/31/2017 11:34 AM
0.01
Amy DiVasta
8.5 Is FDA IND approval pending?
  Yes No
If NO:
8.6 Is this research being conducted under a formal IND exemption request to FDA?
  Yes No
If YES:
8.7 Upload a copy of the FDA letter granting the IND exemption.
Name
Date Last Modified
Version
Owner
There are no items to display
If NO:
8.8 Please confirm each statement or provide a justification for each criteria for IND exemption: 
8.8.1 The drug product is lawfully marketed in the United States.
  Yes No
8.8.2 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


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change in the labeling of the drug.
  Yes No
8.8.3 In the case of a prescription drug, the investigation is not intended to support a
significant change in the advertising for the drug. 
  Yes No
8.8.4 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.
Please explain how the use outside of the approved labeling does not put participants at
increased risk due to participation in the study: 
8.8.5 The investigation is conducted in compliance with the requirements for review by an IRB
and with the requirements for informed consent.
  Yes No
8.8.6 The investigation is conducted in compliance with the requirements of 21 CFR 312.7 (i.e.
the investigation is not intended to promote or commercialize the drug product). 
  Yes No
8.8.7 Please provide any additional information if necessary. 
9
* What is the dosage, route of administration or application, and frequency and total duration of use of the
product? 
cabergoline 0.5 mg by mouth administered twice weekly for 6 months
10
* What is the proposed mechanism of action of the product? Include any post-manufacturing modifications to
the product expected to affect the proposed mechanism of action.
Analysis of endometriotic lesions has demonstrated that a prerequisite for their formation and maintenance is the
development of an adequate blood supply. The regulation of this ‘‘endometriotic vasculature’’ involves well-established
pathways of angiogenesis, including vascular endothelial growth factor (VEGF) acting through the VEGF receptor 2
(VEGFR2). 
Cabergoline is a long-acting dopamine receptor agonist with a high affinity for D2 receptors, a Drd2-A. In animal models,
Drd2-A inhibit pathologic angiogenesis by inactivating VEGFR2 signaling while maintaining an acceptable safety profile
and not interfering with the normal establishment and progression of pregnancy.
In a preliminary study that sought to evaluate the efficacy of Drd2-A in the treatment of peritoneal endometriosis in
humans, researchers found that Drd2-A led to tissue degeneration, which was supported by down-regulation of
VEGF/VEGFR2, three proangiogenic cytokines (CCL2, RUNX1, and AGGF1) and plasminogen activator inhibitor (PAI)
1,
a potent inhibitor of fibrinolysis in the L2 lesions
11
List any contraindications or potential drug interactions.
Potential Drug Interactions:
Ergot-alkaloids, macrolide antibiotics, other dopamine agonists (phenothiazines, butyrophenones, thioxanthenes, or
metoclopramide)
Contraindications: 
- uncontrolled hypertension,
- a history of pulmonary, pericardial and retroperitoneal fibrotic disorders
- a history of cardiac valvulopathy of any valve
• a known hypersensitivity to this drug or any ergot derivatives and to any ingredient in the formulation
12
Are there any known antidotes? Please describe.
In cases of overdose, symptoms of overdose would likely be those of over-stimulation of dopamine receptors. These
might include nausea, vomiting, gastric complaints, hypotension, or thought/perception disturbances (hallucinations),
nasal congestion and syncope.
General supportive measures should be undertaken to remove any unabsorbed drug and maintain blood pressure if
necessary. In addition, the administration of dopamine antagonist drug may be advisable.
13
* Will subjects, or their insurance providers, be charged for the investigational product?
  Yes No


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14
Please upload any additional documents, including the approved drug label or package insert.
Name
Date Last Modified
Version
Owner
 Dostinex prescribing information
6/3/2015 12:55 PM
0.01
Amy DiVasta
 Dostinex prescribing information 2
6/3/2015 12:55 PM
0.01
Amy DiVasta
 
ID: VIEW470A4FA4F4400
Name: Use of an Approved Drug/Product for an Unapproved Indication 
Drug/Product used under Approved Labeling
1
* Select the type of product that will be administered that is relevant to the aims of the research
protocol.  If there is more than one product which is relevant to the aims of the protocol, enter
information about one product at this time.  You will be able to enter additional products at a later
time.  
Drug
Biologic
Combination
Other
If Combination:
  Please describe. Include whether it is regulated as a drug/device/biologic. What is the mode of
action?
If Other:
  Please describe: 
2
* What is the generic name or descriptor of the product?
norethindrone acetate
3
 If any, what is the commercial/trade name of the product?
Aygestin
4
* Who is the manufacturer of the product?
Amneal Pharmaceuticals
5
* Who is the supplier of the product?
Amneal Pharmaceuticals
6
* What is the dosage, route of administration or application, and frequency and total duration of use of
the product?
norethindrone acetate 5 mg by mouth daily for 6 months
7
* Will subjects, or their insurance providers, be charged for the investigational product?
  Yes No
8
Please upload any additional, pertinent documents.
Name
Date Last Modified
Version
Owner
 Aygestin prescribing information
6/3/2015 12:56 PM
0.01
Amy DiVasta
 
ID: VIEW470A5B5BA5400
Name: Drug/Product Used Under Approved Labeling  

SAP_001.pdf: 
Principal Investigator: 
 
Amy D. DiVasta, MD 
Protocol Title: 
Novel Treatments for Endometriosis (NOTE): Dopamine 
Receptor Agonist Therapy for Pain Relief in Women Suffering 
from Endometriosis Pilot Study 
IRB Number: 
RB-P00018628 
NCT Number: 
NCT02542410 
Document Date: 
 
 
June 11, 2019 
 
 


Statistical Plan 
The primary test of interest for the trial is a comparison of the mean change in pain score, as 
measured by the BPI, between groups over time. A linear mixed-effects model will be used to 
estimate the change over time within each group; the model will include fixed effects for group, 
time, and the group by time interaction and random effects for subject and time (to account for 
the correlation among observations from the same subject). Estimates and 95% confidence 
intervals for group differences at each time point will be created using linear contrasts. This 
pilot study is not designed to determine statistical superiority or equivalence of norethindrone 
acetate versus cabergoline; rather, the estimates obtained from the mixed model will be used 
to plan a future randomized controlled trial.  Secondary endpoints will be analyzed similarly. 
Sample Size: As the proposed investigation is a pilot study, the sample size has been chosen to 
provide estimates for the change over time in each group while minimizing the number of 
subjects exposed to the study treatments. Assuming that we will have an 80% trial completion 
rate, we will recruit 7 patients to each arm in order to have 5 completers in each randomization 
group.