Ms. Montana Watnasuvisuth
Beckman Laser Institute
1002 Health Sciences Road East
Irvine, CA 92612
Phone: 949-824-9265
Fax: 949-824-8413
E-mail: mwatnasu@uci.edu
Number of Human Subjects projects reported: 1
"A Center of Excellence for Laser Applications in Medicine"
Principal Investigator: Dr. Michael W. Berns, UC Irvine
Project started in: 1991
Funding for Human Subjects Research:
This project involves the use of multiple protocols/subprojects.
Number of protocols/subprojects associated with this project: 3
Institutional Review Board (IRB) Review:
Type of Review: Full Board
Approving Institution: Beckman Laser Institute/UC Irvine
Most recent approval: 11/27/00
IRB approval number: HS 95-563
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 34
Reporting period for number of human subjects:
Fiscal Year 2001
Type(s) 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 of 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.
Institutional Review Board (IRB) Review:
Type of Review: Full Board
Approving Institution: Beckman Laser Institute/UC Irvine
Most recent approval: 06/26/00
Explanation of IRB approval:
Pending IRB approval.
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 0
Reporting period for number of human subjects:
Fiscal Year 2001
Type(s) of Human Subjects Involvement:
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 Photodynamic therapy (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.
Institutional Review Board (IRB) Review:
Type of Review: Full Board
Approving Institution: Beckman Laser Institute/UC Irvine
Most recent approval: 08/02/01
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 12
Reporting period for number of human subjects:
Fiscal Year 2001
Type(s) of Human Subjects Involvement:
Objective:
The objective of this study is to determine the degree of PWS lightening and the incidence of side effects during treatment with the 1500 ms pulsed dye laser in association with CSC (ScleroPLUS) at high incident light dosages.
Methodology:
A port wine stain (PWS) is a vascular malformation found in approximately 0.3% of children. These lesions are generally noted at birth as a faint pink macule which, as the patient ages, thickens and darkens to a red-purple color. Histologically, PWS birthmarks consist of dermal, dilated, capillary-like vessels with no endothelial proliferation.
PWS birthmarks may be located anywhere on the body but are commonly found on the face and neck where they have serious psychological consequences. Patients are often perceived by others as "marked" which may adversely affect personality development. For this reason and because PWS birthmarks are unlikely to involute with time, patients or their families often seek treatment.
Developing acceptable treatment options has been difficult. Early attempts at treatment included cosmetic cover-up, skin grafting, radiation, dermabrasion, cryosurgery, tattooing and electrotherapy but none of these modalities provided cosmetically acceptable results. The development of lasers and their ability to damage PWS blood vessels offered another treatment option. A variety of lasers have been utilized for the treatment of PWS birthmarks but the flashlamp-pumped pulsed dye laser (FLPDL) has offered the best results with the lowest incidence of side effects.
The FLPDL has become the treatment of choice for PWS birthmarks; however, therapeutic challenges remain. Unfortunately, for many lesions, the threshold for epidermal damage following laser therapy is lower than that for permanent blanching of the PWS. As a result, only 10-20% of patients obtain 100% fading of their PWS even after many treatments.
Clinical studies have demonstrated the efficacy and safety of cryogen spray cooling during pulsed laser treatment of PWS birthmarks. This technology allows the use of higher incident laser light dosages and has been demonstrated to improve treatment results. CSC also decreases treatment pain and the duration of post-laser treatment purpura.
Currently, Candela’s (Wayland, MA) ScleroPLUS provides CSC in combination with a tunable dye laser offering wavelengths from 585-600 nm and a pulse duration of 1500 ms. This laser is FDA approved and is currently being utilized for treatment of PWS birthmarks at the Beckman Laser Institute and many other laser clinics across the country.
Ionizing Radiation, Radioactive Substances, or Chemical Substances:
None
Involvement of Human Subjects:
1. Procedures:
Subjects will be recruited from previously treated and untreated patients at the Beckman Laser Institute seeking removal for PWS birthmarks.
The PWS will be treated with a cryogen spurt of 10-100ms, a delay of 10-60 ms and light doses of 6-15 J/cm2. Patients will have repeat treatments every 8-12 weeks until the completion of the study or such time as they no longer desire treatment with the ScleroPLUS laser. After each treatment patients will be asked to describe the pain as none (0), slight (1), moderate (2) or severe (3). Patients will also be monitored for any adverse effects.
2. Risks:
Possible adverse reactions associated with the proposed laser procedure include:
-scarring
-pigmentary change
-atrophy
-infection
-induration
-pain
-edema
-frostbite
-local skin allergic reaction to the cryogen
A low incidence of mild side effects was reported in clinical trials performed by Candela. This has been confirmed by our own experience with this laser over the past 6 months.
Safety will be evaluated at each visit by asking the patient about any adverse effects and by evaluating the treatment area for scarring, pigmentary change, atrophy or induration. Photographs will be taken at each visit to document treatment efficacy as well as any adverse effects.
3. Privacy/confidentiality/consent:
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 respect to 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. The records and results of these studies will not be identified as pertaining to a certain patient without his 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.