Ms. Christine
A. Anderson
Beckman Laser Institute
1002 Health Sciences Road East
Irvine, CA 92612-
Phone: 949-824-4711
Fax: 949-824-8413
E-mail: anderson@bli.uci.edu
Number of Human Subjects projects reported: 1
Project Identifier:
BLI-91-ER61227
Project Title:
"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
Most recent IRB approval: 02/03/99
IRB approval number: HS 95-563
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 1
Reporting period for number of human subjects:
Fiscal Year 1999 (10/1/98-9/30/99)
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 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
Most recent IRB approval: 05/14/99
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 1999 (10/1/98-9/30/99)
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
Most recent IRB approval: 07/24/98
IRB approval number: 96-514
Explanation of IRB approval:
Continuation of protocol pending.
Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 0
Reporting period for number of human subjects:
Year prior to last IRB approval date
Type(s) of Human Subjects Involvement:
Objectives:
The purpose of this study is to determine the safety and efficacy of ALA as a topically applied photosensitizer for photodynamic therapy (PTD) of cervical intraepithelial neoplasia (CIN) II and III in a phase I/II clinical study. CIN is a precancerous stage of the cervix.
Methodology:
Photodynamic therapy (PDT) dates back to the beginning of this century with numerous examples of its application demonstrated in both in vitro and in vivo settings. PDT involves the use of a photosensitizing drug that is activated by light to cause of photoreaction n biological systems. Photosensitizers are unique compounds that have the ability to absorb photons of the appropriate wavelength and subsequently become elevated to an excited state. The excited photosensitizer in turn reacts with a substrate, such as oxygen, to produce highly reactive singlet molecular oxygen which causes irreversible oxidative damage to biological tissues. This phototoxic reaction is a local phenomenon that takes place within the cell on a time scale of microseconds and leads to cell death and tissue necrosis.
Ionizing Radiation, Radioactive Substances, or Chemical Substances:
5-Aminolevulinic acid (ALA) is a 5-carbon aminoketone that is the first committed intermediate in porphyrin biosyntheses. The hydrochloride salt of ALA is the drug entity to be evaluated. The chemistry of the porphyrins and the biosynthetic system responsible for their formation have been extensively reviewed.
Involvement of Human Subjects:
1. Procedures:
We propose to treat 30 patients with CIN II-III with topically applied ALA followed by PDT. Eligible patients will undergo a pregnancy test and a colposcopy of their cervix with photographic documentation of their abnormal lesions. The ALA dose will be fixed (200 mg/ml of ALA), and it will be topically administered in a cervical cap which will rest against the cervix for a period of 1.5 hour. The area will be treated with light immediately following removal of the ALA containing cervical cap after 1.5 hours. The thirty patients will be divided into 5 groups with 6 patients per group (6 patients in each energy density group x 5 light dose groups=30 patients). Each group will be assigned a different light dose beginning at 50 J/cm2 and increasing in 25 J/cm2 increments up to 150 J/cm2. Additional patients will be added if there are safety concerns or technical difficulties during treatment. Documentation of the diseased area before treatment and during follow up will be performed with still photography or video camera. These photographs will be used only for scientific purpose and will not expose other parts on the body. Patients will be treated at the Beckman Laser Institute and Medical Clinic on the main campus of UCI.
2. Risks
The risks of this treatment might include mild discomfort from the tissue biopsy (if indicated), burning, irritation or an allergic reaction such as skin rash and pruritis from the ALA application. Patients may experience a feeling of warmth in the vagina when the laser light is used. Although we demonstrated minimal drug uptake by the normal tissue at 1.5 hours following application, it is still possible that the drug will be taken up by some normal cervical cells and that there will be some destruction of normal tissue. This may result in ulceration beyond what is expected with conventional therapy, or stenosis of the cervical canal preventing menstrual flow. We expect that damage to normal tissue will be minimal (if at all) and less than any other treatment modality currently available for CIN. Other unexpected adverse reactions which may interfere with daily function include intractable pain or other side effects that may require hospitalization. It should be emphasized that these rare side effects may occur following conventional treatment as well.
3. Privacy:
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 their 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 materials become known in the future which might adversely affect their 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.