SIGNATURE PAGE
(Attach to each copy of your proposal)
Fill in all the blanks
Does the subject group include healthy volunteers? _x_Yes __No
Does the subject group include ill persons? __Yes _x_No
Are subject groups excluded for medical reasons? _x_Yes __No
Are there vulnerable subject groups? __Yes _x_No
If yes, is the exclusion criteria for the study specified? __Yes __No _x_NA
Are any subjects under the age of 18? __Yes _x_No
Are any subjects under the age of 12? __Yes _x_No
Are any subjects over the age of 70? __Yes _x_No
Yasmen Simonian
Principal Investigator’s Name Principal Investigator’s Signature Date Department
ysimonian@weber.edu,
Principal Investigator’s email address Mailing Address/Mail Code/City, State, Zip Telephone
Callie Parry, Jacob Barnhill, and Corey Bankhead; Clinical Laboratory Sciences
Student Researcher’s Names Department
Yasmen Simonian
Department Chair’s Name Department Chair’s Signature Date Telephone
A. APPLICATION FORM
1. TITLE
The Effects of Oral Contraceptives on the Levels of Protein C and Protein S.
2. DESCRIPTION OF THE STUDY
The role of Protein C and Protein S in the blood coagulation process is to inhibit certain activated blood clotting factors. Without the inhibition of theses factors, the body may develop increased incidents of blood clots. Oral contraceptives are thought to lower the levels of Protein C and Protein S.
Volunteer participants will be asked to complete a questionnaire to assess their health status, the length, type, and dosage of the oral contraceptives that they are currently using. Same number of healthy female volunteers not on oral contraceptives regiment will serve as the control population. At least 60 healthy and suitable participants will be invited to join the study. Blood samples will be collected in sodium citrate vacutainer tubes for measurements of Protein C and Protein S levels. Appropriate statistical methods will be employed to analyze the collected data.
3. DURATION OF THE STUDY
The study will be carried out during Spring Semester of 2006. Preparation for the study will take place during the remaining of Fall Semester 2005, following IRB approval. Recruitment, completion of questioners and selection of the volunteers will follow. Blood specimen collection will be performed at convenient times for the participants and the investigators. This will be coordinated within a two-day period. Upon preparation of samples, the laboratory testing will be conducted to measure levels of Protein C and Protein S with appropriate coagulation instrument. The statistical analyses will be carried out following the data collection.
4. MULTICENTER STUDY
This study is not a multi-center study and will only require the cooperation of Weber State University Clinical Laboratory Sciences Department.
5. NUMBER OF SUBJECTS
The total number of subjects needed for this study is at least 60.
6. HEALTH STATUS OF THE SUBJECTS
The subjects will be healthy normal adult females, over the age of eighteen, with no known health problems that would interfere with testing.
7. SUBJECT GROUPS EXCLUDED
Subjects diagnosed with lupus, liver disease, renal disease, and diabetes type I will be excluded from the study. Since the above mentioned conditions have been associated with protein C deficiency. Subjects who have not been on or off oral contraceptives for at least two months, due to changing levels of hormones in their system will also be excluded.
8. AGES OF THE SUBJECTS
Subjects must be over the age of 18 and not on menopause to participate in our study.
9. DESIGN OF THE STUDY
Two groups of volunteer subjects will be included in the study. The participants will be placed in a control (not taking oral contraceptives) group and the second population will be placed in the group using oral contraceptives. An unpaired t-test with an alpha level of .05 will be used to assess the null hypothesis that there is no significant difference between levels of Protein C and Protein S in individuals using oral contraceptives compared to individual not using oral contraceptives.
10. RISKS TO SUBJECTS
Trained phlebotomists will collect blood samples from all individuals participating in the study. All participants will be monitored closely for any adverse reactions that may occur due to regular blood draws. The risks to the patient are very minimal and may include minor bruising and or bleeding in the area that the blood specimen is drawn. There is possible risk of dizziness, lightheadedness, feeling faint or possible loosing consciousness during or after the drawing of blood. If any of the above should occur, the phlebotomists will discontinue the draw, and treat with administration of juice and/or elevation of the extremities. The test will be terminated for this individual, and no further attempts will be made to obtain a blood sample from the individual.
11. BENEFITS TO SUBJECTS AND OTHERS
There is no monetary benefit to the subject involved in the study. However, the outcomes from the study will be shared by way of presentations and publications at various levels of professional organizations. If the findings determine that oral contraceptives do decrease levels of Protein C and Protein S, then additional patient education should be in place to advice individuals regarding the risk factors and increased incidences of blood clots.
12. COSTS TO BE BORNE BY SUBJECTS
There will be no cost to the subjects.
13. IS CONFIDENTIALITY ASSURED
WSU Students will be notified of the opportunity to participate in the study by an e-mail memo. Individuals other than students will be informed of the study by a memo handed out. An attachment of the memo is included at the end of this application. A consent form will be given to all individuals prior to their participation in the study. An attachment of the consent form is also included at the end of this application. Adequate time to read the Experimental Subject’s Bill of Rights and to read and sign the consent form will be given prior to participation in the study.
To ensure complete confidentiality, each subjects’ blood sample will be collects as blind samples. Each blood sample and questionnaire will be labeled as consecutive numbers. No subject names will ever be collected.
14. CONTRACT OR GRANT NUMBER
A proposal for continuation of this project will be submitted to the Dumke College of Health Professions Marriott Research Committee.
15. NAME OF PRINCIPAL INVESTIGATOR AND DEPARTMENT
Dr. Yasmen Simonian, the Chair of Clinical Laboratory Sciences (CLS) Department is the principal investigator of the study. The senior students assisting with the study are Callie Parry, Jacob Barnhill, and Corey Bankhead.
B. DESCRIPTION OF THE STUDY
INTRODUCTION:
It has been previously described that there is an increased risk of developing blood clots or deep vein thrombosis (DVT) in women taking oral contraceptives (OC). This study will investigate the possible causes of acquired blood clotting disorders due to OC. The clotting process and breakdown (lysis) of the clot under normal physiological conditions are controlled and balanced (hemostasis). If one or more of the blood coagulation factors, which are a part of the clotting and lysing processes are inhibited, the two paths are no longer in hemostasis. The body will either clot more (thrombosis) or lyse (hemorrhage) more. Protein C (PC) and Protein S (PS) are the two essential factors in circulation that are able to inhibit formation of clots in the blood. These two factors will be the main focus and will be measured in this study. The levels of PC and PS are proposed to be decreased by OC. The hypothesis is that OC not only influence PC levels, it also may affect levels of PS. This study will measure PC and PS levels in a randomized population of healthy women who are taking OC. A second population of healthy women not taking OC, (for at least two months); will be used to determine the baseline values. The intention is to examine the correlation between OC use and the levels of PC and PS. Low levels of PC and PS may lead to increased occurrences of DVT.
1. BACKGROUND INFORMATION
It is estimated that worldwide 100 million women use an OC. With such a large number of individuals taking medication, even the smallest increase in risk of side effects will affect the lives of many. Therefore, knowledge of these risks and efforts to reduce them are of crucial importance.
Protein C’s role in the coagulation pathway is to inhibit activated Factor 8 (VIIIa) and Tissue Plasminogen Activator Inhibitor (TPAI). Protein C in conjunction with Protein S inhibits activated Factor 5 (Va). Without the proper levels of Protein C and S, an individual cannot inhibit the coagulation process as needed. TPAI’s role in the coagulation cascade is to inhibit Tissue Plasminogen Activator (TPA), which activates plasmin that in turn breaks down clots. Without PC, TPAI is not inhibited and the clots will not break down. The study will investigate any correlation between the levels of PC and PS with OC use in a healthy female population.
2. EXPERIMENTAL METHODS
- The study will begin with a questionnaire for possible participants. This will categorize the participants into three groups: acceptable participants, control population, and unacceptable. This questionnaire will also provide information about health status, the length, type and dosage of OC.
- The acceptable participants and control population will have their blood drawn in a sodium citrate tube, suitable for coagulation testing.
- Coulter ACL 100 will be used to test the blood samples for PC and PS levels.
- The data will be examined for correlation between Protein levels, the type and dosage of OC compared to the normal population.
3. DESCRIPTION OF RECRUITMENT PROCEDURES
All on campus students will be notified of the opportunity to participate in the study by an e-mail memo. Individuals other than students will be informed of the study by a memo handed out. An attachment of the memo is included at the end of this application.
C. INFORMED CONSENT
TITLE: Effects of Oral Contraceptives on the Levels of Protein C and Protein S
INVESTIGATORS:
Dr. Yasmen Simonian (801.626.7080), Callie Parry, Jacob Barnhill, and Corey Bankhead. Clinical Laboratory Sciences Department
If there are any other inquiries regarding the process or concerns not directly related to the study, the participants may direct them to the Institutional Review Board (IRB). The following is the name and the contact information for such questions:
Dr. Marjukka Ollilainen, (801.626.6238)
Chair of the IRB committee
PURPOSE OF STUDY:
To determine whether or not oral contraceptive can reduce the levels of Protein C and Protein S, which are needed to maintain blood clots from being formed.
STUDY PROCEDURE RISKS:
There are no serious risks in participating in this research study. There may be very minimal risk that may include minor bruising and or bleeding in the area that the blood specimen is drawn. There may be a possible risk of dizziness, lightheadedness, feeling faint or possible loosing consciousness during or after the drawing of blood. If any of the above should occur, the phlebotomists will discontinue the draw, and treat you with administration of juice. The test will be terminated and no further attempts will be made to obtain a blood sample from you.
BENEFITS:
The intention is to examine the correlation between oral contraceptives use and the levels of Protein C and Protein S. Low levels of Protein C and Protein S may lead to increased occurrences of blood clots. The benefits will be to have increased knowledge regarding the use of oral contraceptives.
CONFIDENTIALITY:
You have a right to privacy. All information that is obtained in connection with this study that can be identified to you will remain confidential. Upon collection, your sample will be assigned a sequential number within the study, and your name will not be associated with the sample number. The principle investigators and other student researchers will examine the data, including the contraceptive use. The results of this study will be used in presentations and may be used in a paper to be published in a scientific journal, but no individual participant will be identified by name.
VOLUNTARY PARTICIPANTION:
Your decision to participate in this study is completely voluntary and you are free to refuse to participate in the study at any time.
CONSENT:
In signing this consent, I have given permission for the investigators to use any results obtained during the test process with the understanding that my identity will be kept confidential. My signature indicates that I have read the above information and I have had a chance to ask questions to help me understand what my participation will involve. I agree to participate in this study. I understand that by signing this form, I have not waived any of the legal rights to which I otherwise would have as a participant in a research study.
Name of Participants (Print)
Participant’s Signature Date
D. EXPERIMENTAL SUBJECT’S BILL OF RIGHTS
The rights below are the rights of every person who is asked to be in a research study.
As an experimental subject, I have the following rights:
1. To be told what the study is trying to find out.
2. To be told what will happen to me and whether any of the procedures, drugs, or devices that are different from what would be used in standard practice.
3. To be told about the frequent and/or important risks, side effects or discomforts of the things that will happen to be me for research purposes.
4. To be told if I can expect any benefit from participating and, if so, what that benefit might be.
5. To be told what other choices I might have and how they may be better or worse that being in the study.
6. To be allowed to ask any questions concerning the study both before agreeing to be involved and during the course of the study.
7. To be told what sort of medical treatment is available if any complications arise.
8. To refuse to participate at all or to change my mind about participating after the study is started.
9. To receive a copy of the signed and dated consent form.
10. To be free of any pressure when considering whether I wish to agree to be in the study.
The Effects of Oral Contraceptives on the Levels of Protein C and Protein S.
Questionnaire
Date__________
Age__________
Sex_________
Circle One
1. Do you currently suffer from any of the following conditions:
Liver disease, renal disease, diabetes type 1, cancer,
or a blood clotting disorder Yes No
2. Are you post menopausal? Yes No
3. Are you currently taking any hormonal contraceptive drugs? Yes No
If yes A. What is the method of delivery of the contraceptive? ___________
Ex. “the pill”, patch etc.
B. What brand is the contraceptive? ____________
C. If known, what is the dosage? ____________
D. How long have you been taking the contraceptive?
0-2 Months 2-6 Months 6+ Months
E. In the last month how often did you miss a dose?
0-2 Times 2-4 Times 4+ Times
If No, Has it been two months or more since you have taken a hormonal contraceptive drug? Yes No
4. Do you have a family history of deep vein thrombosis, or blood clots? Yes No
If Yes, please explain __________________________________
5. Do you smoke, if so how much?
6. Do you drink alcohol, if so how much?
Thank you….
Memorandum
To:
Clinical Laboratory Sciences Senior Students
Date: 10/25/2005
Re: Participants Wanted in Research Study
We are looking for healthy women to participate in our research study.
It has been proposed that oral contraceptives increase the risk of developing blood clotting problems. There are about 100 million women worldwide who use oral contraceptives. With such a large number of individuals on the “pill”, even the smallest increase in risk of side effects will affect many lives. Therefore, knowledge of these risks important and efforts to reduce them are of crucial importance. Your participation in this study would be of great value universally.
If you would like to participate in this research then please come to Marriott Allied Health Building Room 322, January16th 11:00-2:00 or January 18th 11:00-2:00.
REQUIREMENTS:
Complete a questionnaire and have one tube of blood drawn.