Ms. Christine A. Anderson
Beckman Laser Institute
1002 Health Sciences Road East
Irvine, CA 92612
Phone: 949-824-4711
Fax: 949-824-8413
Email: anderson@bli.uci.edu
Projects are approved by an IRB located at: Beckman Laser Institute/UC Irvine.
The approving IRB operates under a Multiple Project Assurance (MPA) recognized by DOE or by the Department of Health and Human Services (HHS).
MPA number of the IRB: M-1305
Number of Human Subjects Projects reported: 1
Project Identifier: BLI-91-ER61227
Project Title:
A Center of Excellence for Laser Applications in Medicine (formally UCI-91-ER61227 in FY97 database)
Principal Investigator:
Dr. Michael W. Berns
Principal Investigator's Institution: UC Irvine
Project started in: 1991
Project Funding Information:
Project received funding in Fiscal Year 1998.
Project used human subjects in Fiscal Year 1998.
Funding Sources:
Total Funding: $114,236
Project involves use of multiple protocols/subprojects.
Number of protocols/subprojects associated with this project: 4
Protocol/Subproject # 1
Protocol/Subproject Identifier: HS 94-200
IRB Review:
Type of Review: Full Board
Most Recent Approval: May 20, 1997
IRB Approval Number: HS 94-200
Number of Human Subjects who participated in this project/protocol during
05/20/97 - 03/31/98: 12
Protocol ended 03/31/98
Type of Human Subjects Involvement:
Objectives:
The objective of the study is to obtain data on dose-ranging, as well as clinical efficacy and safety, on the use of dynamic cooling during pulsed laser treatment of Port Wine Stain (PWS) malformations.
Methodology:
This is a single center, open study to explore dose response relationships of dynamic cooling at varying cryogen spurt durations during pulsed laser exposure, and to determine safety and efficacy in treated patients having PWS. Subjects will be recruited from an on-site population of approximately 250 previously laser-treated or previously untreated patients at the Beckman Laser Institute and Medical Clinic, University of California, Irvine. There are no limitations in terms of skin distribution of the PWS. Successive patient groups will be given longer durations of the cryogen spurt (range 0-20 milliseconds) and within each group, escalating light doses (range 5-10 J/cm2). On each patient, test sites will be compared and evaluated for efficacy and safety of the test doses. Eighteen circular sites will be treated with different cryogen spurt regimes: six sites will be treated without dynamic cooling; six adjacent sites will be treated immediately after a 10 millisecond cryogen spurt; and six adjacent sites will be treated immediately after a 20 millisecond cryogen spurt.
Efficacy will be determined by cryogen spurt duration/light doses necessary to produce clinically significant blanching without adverse effects of treated PWS sites compared to uncooled sites and untreated control sites.
Ionizing Radiation, Radioactive Substances, or Chemical Substances:
None.
Involvement of Human Subjects:
1. Procedures:
Treatment Visit - Patients will be allocated a sequential identification number and assigned to treatment. After such an assignment, all subjects including drop outs must be accounted for and fully documented through withdrawal or study completion. In each subject, 18 test sites on the PWS will be chosen for clinical study. All sites will be circular in shape, 5 mm in diameter and identified by a skin marker. Six sites (numbered 1,4,7,10,13,16) will be selected for irradiation without dynamic cooling. Six adjacent sites (numbered 2,5,8,11,14,17) will be selected for identical light doses of irradiation immediately after a 10 millisecond cryogen spurt. Six adjacent sites (numbered 3,6,9,12,15,18) will be selected for identical light doses of irradiation immediately after a 20 millisecond cryogen spurt. Before laser irradiation, all numbered sites will be photographed under standardized conditions for film, light source and exposure. Incremental dosages of light (range 5-10 J/cm2, in increments of 1 J/cm2) will be applied ranging from the lowest in sites 1, 2 and 3 to the highest in sites 15, 16 and 17. A surgical drape will be used to define the study sites and to protect the remaining skin from exposure. Subjects will wear protective eye glasses to shield their eyes during the light treatment.
2. Risks:
Possible adverse effects are as follows:
- hypertrophic scarring
- changes in the normal skin pigmentation or color
- atrophy
- induration
- frostbite
- local skin allergic reaction to the cryogen
Previous studies cited above using the flashlamp-pumped pulsed dye laser for the treatment of PWS have reported an incidence of adverse effects of less than 2%. Flashlamp-pumped pulsed dye laser treatment is likened to "a rubber band snapping against the skin." We have found the treatment to be well tolerated by adult patients. No local or general anesthetics are required. Prolonged skin exposure to the cryogen can cause frostbite. However, the proposed application of a 0-20 millisecond aerosol cryogen spurt is not expected to cause frostbite and, therefore, does not constitute a significant risk to subjects participating in this study.
The possibility of a local skin allergic reaction to the cryogen does exist and participating subjects will be followed closely. Skin allergic reactions will be assessed on a five point scale:
SCORE SKIN ALLERGIC RESPONSE
1 No reaction; identical to surrounding non-irradiated skin
2 Minimal perceptible erythema; blotchy areas of faint erythema confined to the irradiated site
3 More pronounced, even bright, erythema without edema
4 Marked erythema with edema
5 Violaceous erythema with vesiculation
Adverse Effects Reporting:
Safety will also be evaluated at each visit by searching for any adverse effects such as hypertrophic scarring, changes in the normal skin pigmentation, atrophy and induration. Additional photographs will be taken during the course of the study of any adverse effects. Adverse effects monitoring will consist of those symptoms, complaints, or effects reported by subjects or investigators. Subjects will be asked about their symptoms, complaints, or adverse effects at each evaluation visit, and the information will be recorded on the Adverse Experiences form. Any severe or unexpected adverse experiences, any increase in the frequency of adverse experiences or death that may occur in this study will be reported immediately to the Institutional Review Board together with an evaluation as to whether or not the adverse experience is in any way related to the treatment. The initial report will be made by telephone and will be followed by a complete written report within five working days. The structure of the described protocol, close clinical supervision and an awareness of the potential adverse reactions provide a significant margin of safety for this investigation. Vital signs monitoring will take place only at baseline.
3. Privacy/confidentiality/consent:
Informed consent will be obtained from all subjects. The principal investigator will explain the full details of the protocol, experimental procedure, possible side effects, risks, and complications of the treatment to each participant before informed consent is sought and documented on the standard University of California, Irvine consent form. The subject will then be given the opportunity to sign the informed consent form in the presence of the principal investigator and a witness, who will also sign the informed consent. The patient will be informed that he or she may withdraw his consent at any time during the course of the study without prejudice to further care. The patient will be given a copy of the informed consent to keep, and a copy will be placed as a permanent record in the patient's medical chart. Informed consent will be sought only after the participating physician explains the full details of the protocol, possible side effects, risks and complications to the subject. Consent will be documented by signing the standard University of California, Irvine, form. Explanation will be given of all treatment alternatives with respective advantages and disadvantages. Complete confidentiality will be maintained by staff physicians, nurses, and technical support personnel. A sequential code number for each patient will be kept in a log book and all records stored in a locked file. Patients will be identified only by their corresponding code numbers. The records and results of these studies will not be identified as pertaining to a certain patient without his or her expressed permission to safeguard the confidentiality of the subject. The data assembled will be used for research purposes only to assess the efficacy of the laser therapy and to develop optimum treatment parameters. Study progress will be monitored through monthly Operations Committee meetings. These provide the opportunity to review subject data and ensure the safety of the subjects in the unlikely event of problem situations.
IRB Review:
Type of Review: Full Board
Most Recent Approval: September 23, 1997
IRB Approval Number: HS 95-333
Number of Human Subjects who participated in this project/protocol during
09/22/97 - 04/30/98: 16
Protocol ended 4/30/98
Type of Human Subjects Involvement:
Objectives:
The purpose of this study is to assess the optical properties in uterine tissue by application of a specially-designed intrauterine probe. Routinely, the uterus has to be dilated with a uterine dilator before surgery. The probe will consist of two fibers introduced in the uterine dilator. No other instruments will be used to dilate the cervix other than those used for conventional diagnostic procedures.
Methodology:
Patients scheduled for hysterectomy, dilatation and curettage (D&C), or hysteroscopy will be given an opportunity to participate in in-vivo optical property studies. Optical property measurements will be conducted using a specially-designed frequency domain photon migration (FDPM) measurement probe consisting of a Hegar dilator with source and detector fibers embedded in the outer walls at fixed separations (defined by the dilator diameter). The probe is inserted into the uterus as follows: (1) the external cervical ostium is grasped with a two teeth tenaculum, (2) a hysterometer is inserted to measure the length of the cervical canal and uterine cavity, (3) the photon migration Hegar probe is inserted through the cervical canal to the same depth as measured previously, (4) once the fundus is reached, confirmation of accurate fiber location is provided using ultrasound imaging (the ultrasound probe is turned off during optical property measurements). FDPM measurements are acquired using our 1 GHz portable instrument which is currently able to record data and calculate optical properties in less than 1 minute.
Ionizing Radiation, Radioactive Substances, or Chemical Substances:
None.
Involvement of Human Subjects:
1. Procedures:
The measurement of the optical properties of the uterus will be done at the beginning of the scheduled operation under anesthesia. Routinely, the cervical canal has to be dilated with a uterine dilator before the instrument for D&C or hysteroscopy can be inserted into the uterine cavity. Two fibers placed at opposite sites in specially made channels of the uterine dilator will get in direct contact with the fundus for the measurement of the optical properties. This will add approximately five minutes to the surgical procedure.
2. Risks:
No additional risk or discomfort is anticipated. The average power used for measuring optical properties in the uterus and cervix will be limited to levels (about 50 milliwatts) far below thermal damage thresholds and orders of magnitude lower than conventional light sources used in standard surgical procedures like hysteroscopes and laparoscopes. In addition, light sources will not be turned on until the fibers are positioned inside the uterus correctly. An ultrasound machine will be used to guide the fibers as they are passed to the top of the uterus. There is no risk of damage to the patient from the laser light used to perform the optical measurements. No other instruments will be used to dilate the cervix other than those used for conventional diagnostic procedures.
3. Privacy/confidentiality/consent:
The collection and submission of medical information from this study will be accomplished with the strictest adherence to professional standards and confidentiality. An identification number for each patient will be kept on file, and all records will be filed in a locked area, accessible only to the study physician and his designated assistants. Patients will be identified by initials and a corresponding identification number. A patient profile sheet will be completed for each patient that bears the necessary information needed to contact the patient should new information about the use of the study test articles become known in the future which might adversely affect their well-being. A report of the results of this study may be published but confidentiality will be maintained and names will be known only to the investigator and his technical personnel. Informed consent will be obtained after a detailed explanation of the study has been given, when a patient reports for pre-admittance lab work.
IRB Review:
Type of Review: Full Board
Most Recent Approval: August 31, 1998
IRB Approval Number: HS 95-563
Number of Human Subjects who participated in this project/protocol during
10/10/97 - 08/31/98: 10
Protocol ended 08/31/98
Type of Human Subjects Involvement:
Objectives:
The purpose of this study is to assess the optical properties in breast tissue by application of a specially-designed hand-held probe. The probe will contain optical fibers which will be placed on the surface of a breast and, in the case of surgical measurements, within the open incision in a breast. The probe will emit low intensity red light that is of comparable power to a flashlight and will cause no pain or sensation. No other instruments will be used during the breast biopsy other than those used for conventional diagnostic procedures. No additional risk or discomfort is anticipated. The information gathered from this study will allow for the development a new non-invasive method for breast cancer screening. This study is not a treatment for any disease that influences the indication for any surgery.
Methodology:
Frequency Domain Photon Migration (FDPM) is a technique that uses sinusoidally modulated low-intensity, visible and near infrared light to non-invasively measure the optical properties of tissue. These properties may, in turn, be used to characterize tissue morphology and to determine concentrations of important biomolecules (e.g., hemoglobin, oxyheomoglobin, water, fat). In this study we employ FDPM techniques to make in vivo and ex vivo measurements of human breast, and correlate the results of such measurements with ultrasound, x-ray mammography, and histopathology. For non-invasive measurements, this involves the use of a hand-held optical probe which is placed on the surface of the breast over areas of normal tissues and areas suspected to have abnormalities (i.e., palpable breast lumps). The tissue will in turn be exposed to low levels of red and near-infrared light which is of comparable power to a flashlight and will cause no pain or sensation. Multiple measurements will be made, each lasting about 75 seconds, and the entire measurement process will be approximately 30-60 minutes. For patients undergoing surgical biopsy, the tissue of interest will be exposed using standard surgical techniques and measurements of the lesion and surrounding normal tissue will be made using a modified sterile optical probe. These intraoperative measurements will add approximately 5 minutes to the operation, and there will be no charge to the patient for any extra time due to these optical measurements.
Ionizing Radiation, Radioactive Substances, or Chemical Substances:
None.
Involvement of Human Subjects:
1. Procedures:
If an individual agrees to participate, the following will occur: upon admission of the individual to this study they will have their medical history and laboratory tests reviewed in their records at the University of California, Irvine Medical Center. The non-invasive measurement of the optical properties of the individual's breast(s) will be performed during clinical examination or at a time prior to surgery, either on the day of surgery or on another day agreed upon by the investigators and the individual. Standard clinical ultrasound imaging may also be performed on the individual's breasts for the purpose of determining lesion size and location for comparison with the light measurements. The individual may be asked to wear protective goggles during the light measurements to protect their eyes from the light. A small probe will be placed on the individual's breast(s) for the light measurements and optical properties will be measured. Each light measurement and ultrasound measurement will require about 5 to 10 minutes. The invasive measurements, performed on deep tissues inside the individual's body, of the individual's breast will be during the breast biopsy surgery. A small blunt probe will be placed within the incision made in the individual's breast. Optical fibers placed within channels of the probe will come in contact with the individual's breast tissue and the optical properties will be measured. This will add approximately 5 minutes to the operation and there will be no charge for any extra time due to this optical measurement. The surgical procedure will be performed in the usual manner. Additional measurements may be performed on the biopsy tissue (tissue that is removed) immediately following surgery.
2. Risks:
In the case of surgical patients, the length of the individual's surgery and anesthesia time will be slightly longer in this study and the chance of infection may be minimally increased. However, the patient will be monitored very closely during this time and no significant increase in risk is anticipated. No additional risk or discomfort is anticipated. No other instruments will be used in the breast biopsy other than those used for conventional surgery. During the surgery, the patient's face will be behind an opaque sheet and there will be at no risk of injury to the patient's eyes. During the non-invasive measurement, great care will be taken to only turn the laser on during the measurement. Furthermore, the individual will wear protective goggles to prevent laser injury to their eyes.
3. Privacy/confidentiality/consent:
Informed consent for research will be obtained when the patients are scheduled for surgery and a detailed explanation of the study will be given. The collection and submission of medical information from this study will be accomplished with the strictest adherence to professional standards and confidentiality. An identification number for each patient will be kept on file, and all records will be filed in a locked area, accessible only to the study physician and his designated assistants. Patients will be identified by initials and corresponding identification number. A locator sheet will be completed for each patient that bears the necessary information needed to contact the patient should new information about the use of the study test articles become known in the future which might adversely affect that patient's well-being. A report of the results of this study may be published; however, confidentiality will be maintained and names will be known only to the investigator and his technical personnel.
IRB Review:
Type of Review: Full Board
Most Recent Approval: March 10, 1998
Number of Human Subjects who participated in this project/protocol during
03/10/98 - 09/30/98: 0
No subjects enrolled at this time.
Type of Human Subjects Involvement:
Internal use of chemical substances (solid, liquid, or gas) in human subjects.
Objectives:
The objective of the proposed clinical study is to determine the efficacy and safety of photodynamic treatment of the endometrium after topically applied 5-Aminolevulinic acid is injected into the uterine cavity using a fixed drug dose and application schedule and variable light dose.
Methodology:
This is an open label study designed to assess the safety and efficacy of topical ALA in Hyskon R and red laser light (635 nm) for PDT of the endometrium.
One and one-half milliliters of pH adjusted ALA/HyskonR will be injected into the uterine cavity through a smooth, fine catheter 4-7 hours prior to light application. One ml of fluid is needed to cover the entire cavity of a normal size uterus as demonstrated in hystero-salpingography. This volume covers the walls of the entire uterine cavity without spillage through the fallopian tubes. Up to 12 patients will be enrolled into study during a period of 12 months.
Ionizing Radiation, Radioactive Substances, or Chemical Substances:
Pharmacology of ALA - the product will consist of a solution of 600 mg ALA in 1.5 mL dextran 70 (32% W/V) in dextrose (10% W/V; HyskonR). The crystallized 5-Aminolevulinic acid will be dissolved to 400 mg/mL in HyskonR and titrated with NaOH to pH 6 extemporaneously just before use under sterile conditions.
The light diffuser (L-IUD) is similar in shape and size to a contraceptive intra uterine device. It contains trifurcated transparent plastic tubes that fits the size and shape of the uterine cavity. One laser diffusing fiber is inserted into each tube.
The topical application of the ALA solution will be performed in lithotomy position 4, 5 1/2 or 7 hours prior to light application.
The light intrauterine device will be inserted while the patient is in lithotomy position. The uterine cavity will be illuminated with red light of 635 nm wavelength from a Coherent Medical Model 920 argon pumped dye laser.
Involvement of Human Subjects:
Twelve patients with chronic dysfunctional uterine bleeding who did not respond to conventional treatment and surgical intervention are justified, or patients with stage I cervical cancer who are scheduled for cone (LEEP) biopsy and simple hysterectomy will be asked to enroll into this study.
Risks:
PDT as compared to all other surgical procedures for endometrial ablation is low risk. However, there is a minimal risk of perforating the uterus during insertion of the drug or the light cannula. If this happens the procedure will be terminated and appropriate treatment will be given. All adverse experiences will be recorded in the case report form. Patients may be discontinued from the study prior to its completion for the following reasons:
1) Development of a severe adverse reaction before or during PDT.
2) Patient requests to withdraw from the study.
3) The investigator decides it is the patient's best interest to be withdrawn.
4) Intercurrent illness which may, in the judgment of the investigator, significantly affect assessments of clinical status.
5) Non-compliance.
Safety analysis will be performed on all subjects who receive treatment. Safety will be assessed by compilation of adverse even data including the expected PDT-related symptoms at the treatment site, such as subject discomfort.
Confidentiality:
The collection and submission of medical information from this study will be accomplished with the strictest adherence to professional standards and confidentiality. An identification number for each patient will be kept on file, and all records will be filed in a locked area, accessible only to the study physician and his designated assistants. Patients will be identified by initials and corresponding identification number. A locator sheet will be completed for each patient that bears the necessary information needed to contact the patient should new information about the use of the study test articles become known in the future which might adversely affect their well-being. The FDA may inspect the study and medical records.